theme. We are also the

subject of a dedicated

fundraising appeal by the

University’s Develop-

ment Office. BCV clearly

has a role to play in stra-

tegic research develop-

ment, and for this reason

we are looking to hold a

PI day in September

2016 in order to in-

crease awareness of cur-

rent and forthcoming

projects. This will be an

excellent means of rais-

ing the profile of the

Theme and exploring

new avenues for re-

search and collaboration

amongst senior staff. Fur-

ther details will follow

once known.

Welcome to the latest

installment of the BCV

Newsletter. Please do

take the time to read

about successes of the

BCV community, includ-

ing the election of Dr

Chiara Bucciarelli-Ducci

to a post at the Europe-

an Society of Cardiolo-

gy; a £250,000 grant to

Prof Massimo Caputo

for stem cell treatment

research for hole in the

heart; and a Stroke

Association Lectureship

for Dr Phil Clatworthy.

In December I sent out

a call for Early Career

Researcher (ECR) rep-

resentatives for the

Theme ’ s S t ee r i n g

Group. BCV cannot

meet the requirements

of its postgrads and

postdocs without dedi-

cated voices to guide us.

Our current rep’s term

of office ends in March,

and we would urge PIs

to nominate or encour-

age ECRs to volunteer

to fill this vacancy. Prep-

arations for the next

ECR event taking place

on 15 April are well un-

derway, and input from

the ECRs themselves

into how best to serve

them is invaluable.

Please could I ask all PI’s

to encourage ECRs in

their labs to attend such

events. By bringing ECRs

into contact with differ-

ent expertises and inter-

ests we give them a

broader knowledge of

the career paths a cardi-

ovascular scientist can

pursue, the potential for

collaboration, and a

chance to network be-

tween Schools and or-

ganisations. This benefits

them, their work and

their lab. I very much

hope, therefore, that all

PI’s will support these

initiatives.

The Biomedical Review

designated Bristol Car-

dio-Vascular as a flagship

Welcome by Rob Tulloh, Chair of BCV

Bristol

CardioVascular

Newsletter January-February 2016

bcv-info@bristol.ac.uk

/cardiovascular

0117 931 7610

BCV seminars

INSIDE THIS

ISSUE:

Welcome 1

Events 2

News 3

EBI Funding 13

H2020 13

Funding Opps 14

Showcase 24

Recent Pubs 25

Contacts 33

Studies of atrial fibrillation

15 February 2016, 13.00-14.00. Andy James, E29 Biomedical Sciences

Building

Fellowship Bootcamp 2016

16 February 2016, 12.00-17.00. Room 4.10, 35 Berkeley Square. Registra-

tion required.

Angiotensin Gordon Research Conference

21 February 2016, 9.00-17.00. Keynotes: Armin Kurtz (Regensburg), Xavi-

er Jeunemaitre (Paris), Il Ciocco Resort & Spa, Barga, Lucca, Italy

Clinical Research & Imaging Centre Research Showcase 2016

29 February 2016, 9.00-17.00. Watershed. Registration required.

Dynamic interactions between normal and malignant haematopoietic cells

7 March 2016, 13.00-14.00. Cristina Lo Celso (Imperial College London),

E29 Biomedical Sciences Building

Why we should all care about adding fats to proteins

14 March 2016, 13.00-14.00. Will Fuller (University of Dundee), St

Michael's Hill 31-37, room A1.4

Chromatin structure and cellular identity

17 March 2016, 13.00-14.00. Abdenour Soufi (Group Leader, MRC Cen-

tre for Regenerative Medicine, University of Edinburgh), C42, Biomedical

Sciences Building

Surgical Trials Showcase 2016

18 March 2016, 9.00-17.00. M-Shed

Mapping of the cardiac conduction system - from cell to bedside

25 April 2016, 13.00-14.00. Halina Dobrzynski (University of Manchester,

E29 Biomedical Sciences Building

Feel It Festival

12-19 October 2016

EVENTS

Early Career

Researchers’

event

15 April 2016

9.00-13:30

room 4.10

35 Berkeley

Square

Call for

abstracts

now OPEN

Page 2 Bristol CardioVascular Newsletter

An investment of

£150,000 on behalf of

the Elizabeth Blackwell

Institute for Health Re-

search, through its

Wellcome Trust ISSF

Award (match funded

by the University of

Bristol), will fund three

new posts that will be

openly available to help

support all health and

biomedical researchers

across the University in

their informatics needs.

These posts will come

into full effect in the

early part of 2016, and

will comprise:

i) A Biomedical Research

Computing Analyst based

in the Advanced Compu-

ting Research Centre

who will enable re-

searchers working with

high throughput, multi-

omic data and complex

modelling to have en-

hanced access to the

University's HPC and

Research Data Facilities

in order to generate, re-

fine and optimise the re-

search software they

specifically need.

ii) A Genome Informati-

cian located in the Life

Science Building ‘Omics

Hub’ with expertise in

Galaxy software and

who will support re-

searchers analyse deep

sequencing, RNA-seq

and CHiP-seq

iii) A Microscopy Image

Analyst based in the

Wolfson BioImaging Fa-

cility in the Biomedical

Sciences Building to help

researchers with their

image processing and

analysis needs. Dr Ste-

phen Cross has been

appointed into this role

and is expected to be in

post on 1 February

2016.

Health and Biomedical IT support

Page 3

New translational research centre

The £5.3 million Translational Biomedical Research Centre (TBRC), currently under

construction at Langford, aims to get research out of the laboratory and ensure patients

worldwide can access ground-breaking treatments as quickly as possible. Funded by UoB,

MRC and BHF, the centre’s ‘topping-out’ was celebrated in September, led by the Centre’s

Director, Professor Raimondo Ascione.

TBRC will use experimental models relevant to human disease and anatomy and procedures

will be tracked in living animals using non-invasive scanning techniques. This will help test new

treatments to NHS standards while reducing the number of animals needed. It will operate

under the One-Health concept for the benefit of people, animals and environment. This is a

key development in the University’s vision for a research culture that feeds directly and rap-

idly into tangible and lasting benefits for the health and welfare of humans and animals alike.

NE

WS

Dr Andrew James, PI,

and co-applicant Prof

Jules Hancox have

been awarded a Pro-

ject Grant from the

British Heart Founda-

tion. They received

£226,944 to study Se-

lective late sodium cur-

rent blockers as anti-

arrhythmic drugs in atrial

fibrillation over the next

three years.

Dr Sebastian Oltean,

PI, and Professor Steve

Prof Mark Cannell, PI,

with co-applicants Prof

Jules Hancox, Dr Guil-

laume Chanoit and

Prof Godfrey Smith

(Glasgow) have been

awarded an MRC Pro-

gramme Grant to study

the Relationship between

early and late events in

the cardiac cycle as con-

trol points for therapeutic

intervention. The five

year award is worth

£1.45M.

Harper, co-applicant,

have been awarded a

British Heart Founda-

tion grant. The project

will look at mRNA

splicing control in dia-

betes: a novel therapeu-

tic strategy for treatment

of diabetic nephropathy.

The amount o f

£268,270 has been

awarded for three

years.

Stroke Association Lectureship

Recent Funding Successes

Page 4 Bristol CardioVascular Newsletter

following brain injury

with a view of devel-

oping individualised

visual rehabilitation.

This work is directed

toward improving

health using stratified

(or personalised) med-

icine, a major priority

area in medical re-

search. His work fo-

cuses on rehabilitation

of brain injury, and

enhancement of re-

covery using pharma-

cological and non-

pharmacological meth-

ods (e.g. non-invasive

brain stimulation).

Dr Phil Clatworthy has

been awarded the

Stroke Association

Thompson Family Sen-

ior Clinical Lecture-

ship. The award will

enable Phil to advance

his research on vision

in stroke alongside his

clinical practice as

Consultant Stroke

Neurologist at North

Bristol NHS Trust. Phil

was awarded an EBI

Early Career Fellow-

ship in June 2014 to

work on understand-

ing brain plasticity and

perceptual learning

There is also a strong

neuroscience compo-

nent in this research,

aimed at understand-

ing mechanisms under-

lying recovery and re-

habilitation, which he

has been developing

with groups within the

University. Phil is look-

ing to develop a re-

search group at UoB

and welcomes enquir-

ies from people inter-

ested in working in his

research area–

contact him on

phil.clatworthy@brist

ol.ac.uk.

Follow Phil on his blog

Research has taken

the first steps towards

new treatments for

inherited diseases such

as cystic fibrosis, one

form of Bartter’s syn-

drome, and two

forms of myotonia

which are linked to

defective movement of

anions across cell

membranes.

To develop artificial

anion transporters

Prof Tony Davis, Dr

David Sheppard and

colleagues synthesised

molecules with two

distinct parts. One

was designed to bind

lipids; the other to

form a cage-like struc-

ture to hold a chloride

ion and protect it.

These anionophores

bind a chloride ion on

one side of the cell

membrane, shielding it

from lipids as it is

shuttled across the

membrane, and then

releasing it on the oth-

er side.

Dr Hongyu Li tested

15 anionophores on

individual cells and epi-

thelia. By monitoring

chloride transport in

real time through

changes in cell fluores-

cence or electrical ac-

tivity, he identified one

compound with special

p rom i se : b i s - ( p -

n i t r o p h e n y l )

ureidodecalin. Of spe-

cial interest are: a) it

was deliverable to cell

membranes, b) it ex-

hibited robust activity

as an anion trans-

porter approaching

levels achieved by nat-

ural anion transport

A £250,000 grant goes

towards the Good

Manufacturing Practice

phase of this research,

which has yielded ex-

cellent results so far.

This could have great

benefits for babies

born with hole in the

heart, requiring them

Massimo Caputo, Pro-

fessor of Congenital

Heart Surgery, has

been developing stem

cell patches for babies

to replace the current

patches that do not

grow with the child

and often lead to re-

peated operations.

to have less surgery

and reducing the risk

of complications.

This next phase will

refine the tissue engi-

neering process, after

which it is hoped to

lead to clinical trials.

New therapy for diseases caused by defective anion transport

Enid Linder Foundation grant for Hole in the Heart

The proposed mechanism by

which the anionophore

works. In this case, chloride

ions on one side of the cell

membrane are exchanged

for iodide ions as the

anionophore shuttles anions

across the cell membrane.

Page 5

pathways, c) its ac-

tivity was long last-

ing, transporting

chloride for about

two hours following

a 10-min treatment

period, d) it showed

no evidence of tox-

icity when tested on

three different types

of cells, e) its chemi-

cal properties ap-

proach those of

drug-like chemicals.

cal Veterinary Primer.

Primers Clinical pri-

mers are aimed at

Medical & Veterinary

clinical graduates and

are designed to give

outstanding early ca-

reer clinicians the

chance to experience a

Congratulations to

Alex Smith (Schools of

Physiology, Pharmacol-

ogy and Neuroscience,

and Veterinary Scienc-

es) for being awarded

a 2015 Elizabeth Black-

well Institute for

Health Research Clini-

world-class research

environment for the

first time. His project

is entitled Novel pacing

device for improving car-

diac output.

Graft for Congenital Heart Disease

Page 6 Bristol CardioVascular Newsletter

as the heart outgrows

the graft.

PI Paolo Madeddu,

Professor of Experi-

mental Cardiovascular

Medicine, is working

on grafts that are able

to grow like living tis-

sue, meaning that mul-

tiple operations could

be avoided.

Nine-year-old Calum,

pictured left, was born

with truncus arterio-

sus, a rare condition

which means that the

two main arteries

which supply blood to

the lungs and the body

do not arise normally

from the heart. Calum

had open heart sur-

gery when he was just

10 days old. He had

two further operations

A BHF award of

£170,000 will support

the development of a

graft which may reduce

the amounts of surger-

ies required to treat

children born with cer-

tain types of congenital

heart disease.

The only treatment for

these conditions is cor-

rective surgery; how-

ever this surgery often

has to be repeated

throughout childhood

when he was four and

six years old, and he is

scheduled to have a

further open heart

surgery next year. His

mother confirms,

“After an operation

two years ago he was

in intensive care for 24

hours and had to have

intravenous antibiotics

for three months af-

terwards. He’s missed

an awful lot of school

over the years. But as

well as the physical

there’s the psychologi-

cal impact. Calum has

had nightmares a re-

sult of what he’s been

through.” Reducing

the number of opera-

tions would have a

hugely positive impact

on their lives.

EBI Clinical Primer award

Cardiology consultant

lecturer Dr Chiara

Bucciarelli-Ducci is

now the Vice-Chair

for Cardiac Magnetic

Resonance Imaging, a

two-year position that

will lead to her taking

the Chair in 2016-18.

The European Society

of Cardiology repre-

sents more than

85,000 cardiology pro-

fessionals from Europe

and the Mediterranean

basin and is the largest

professional body of

cardiologists world-

wide. Its mission is to

reduce the burden of

cardiovascular disease

in Europe. The ESC

provides education

courses and confer-

ences, conducts sur-

veys on specific dis-

ease areas, produces

clinical practice guide-

lines and publishes 12

of the world’s leading

journals on cardiology.

Cardiologist elected to post with the ESC

Page 7

Prior to human trials,

some treatments are

tested in animals, but

only when there’s no

other way to confirm

they are safe and have

beneficial health out-

comes.

Researchers use ex-

perimental models

that are relevant to

human disease and

anatomy, and perform

the tests in state-of-

the-art translational

facilities, such as the

TBRC.

The Centre will bene-

fit from clinical and

academic veterinary

expertise on site and a

state-of-the-art imag-

ing scanner and cathe-

ter lab, allowing re-

Professor Raimondo

Ascione’s balance of

surgeon and research-

er has made him the

perfect candidate to

lead the new Transla-

tional Biomedical Re-

search Centre (TBRC)

in Langford. Its role is

to get research out of

the laboratory, to a

point where patients

worldwide can access

groundbreaking treat-

ments as quickly as

possible.

Translational medicine

aims to take lab sci-

ence performed in vitro

and prove it has posi-

tive healing effects on

a whole living organ-

ism. If so, it can be

considered for human

trials.

searchers to take re-

peated scans of living

animals. This will help

scientists test new

treatments to NHS

standards and signifi-

cantly reduce the

number of animals re-

quired.

There’ll also be a bi-

obank on site which

will reduce future

need for animal tissue

samples. The TBRC

will follow the One

Health initiative to

Heart Matters: Turning Research into Reality

benefit people, ani-

mals and the envi-

ronment. Research

done here will im-

prove the lives of

many animals.

Extract from an article

from Health Matters,

the British Heart

Foundation magazine,

available online.

to actin filaments. The

images obtained are

used to make 3D maps

of the proteins which

are evaluated and in-

terpreted through

known structures of

actin to help identify

the proteins of inter-

est.

These maps are then

deposited into online

databases which are

freely accessible for

comparison with other

research projects.

Dr Paul returned to

work recently after a

A highlight in the Brit-

ish Heart Foundation

magazine Heart Matters

focussed on Dr Dan-

ielle Paul, who uses

electron microscopes

to examine proteins

within heart muscle in

both relaxed and active

states. The EM images

are used to create 3D

‘molecular movies’ of

how the heart func-

tions normally and

when it is diseased.

Danielle is specifically

interested in proteins

that regulate muscle

contraction and attach

career break in 2002.

During this time imaging

techniques changed

quite drastically; in her

case, she missed the

cryo-EM revolution. A

BHF Career Re-entry

Research Fellowship has

helped Danielle gain the

necessary skills and

equipment to advance

in the industry. She was

awarded £207,979 over

three years to build a

structural picture of

heart muscle at a mo-

lecular scale which

could help inform new

drug design.

Clinical Research Training Fellowship

Page 8 Bristol CardioVascular Newsletter

Dr Martin Lewis has been awarded a three year MRC Clinical Research

Training Fellowship (CRTF) worth £226,000 to work with Professors

Saadeh Suleiman & Clive Orchard on a project entitled The Cardiac Role of

the Exchange Protein Directly Activated by cAMP (Epac) During Postnatal Devel-

opment. He will be joining the School of Clinical Sciences on 3 February

2016. on obtaining the above award. The CRTF supports clinically active

professionals within the UK to undertake a higher research degree.

Molecular Protein Structures in Heart Muscle

New Facility for CRIC

The Clinical Research and Imaging Centre (CRIC) now have a new publi-

cations page on their website which displays a comprehensive list

of publications drawn from research that took place there.

The recent development of a

system that predicts how to

create any human cell type

from another cell type directly

has resulted in Mogrify, a com-

putational algorithm which

Bristol lead Prof Julian Gough

and then-PhD student Dr Ow-

en Rackham spent five years

building up. The algorithm is

used to predict the cellular

factors for cell conversions

and was conceived from data

collected as a part of the FAN-

TOM international consortium

based in Japan.

Mogrify will allow experimental

biologists to bypass the need

to create stem cells. Since

the first artificial pluripotent

stem cells were created in

2007, only a handful of fur-

ther conversions have been

discovered; the algorithm

predicts how to create any

human cell type from any

other cell type directly. It

was tested on two new hu-

man cell conversions, and

succeeded first time for

both. The speed with which

this was achieved suggests

Mogrify will enable the crea-

tion of a great number of

human cell types in the lab.

This ability will lead directly to

tissue therapies of all kinds, to

treat conditions from arthritis

to heart disease. The fuller un-

derstanding, at the molecular

level of cell production leading

on from this, may allow re-

searchers to grow whole or-

gans from somebody's own

cells.

Rackham OJ, Firas J, Fang H et

al. (2016). A predictive compu-

tational framework for direct

reprogramming between hu-

man cell types. Nature Genetics.

Published online 18 January

2016.

New Blood and Transplant Research Unit

Page 9

Human Cell Transformation

A partnership between

UoB and NHS Blood and

Transplant has announced

a new £3M NIHR Blood

and Transplant Research

Unit which will advance

research on the manufac-

ture of red blo9od cells

from stem cells and their

translation from the lab

to human trials. This will

aid the development of

red blood cell products to

support transfusion needs

of patients with rare

blood groups and those

with complex and life-

limiting conditions. Lead

applicant Dr Ashley Toye

confirmed that the Unit’s

research would include a

clinical trial of small vol-

umes of artificial blood in

human volunteers and the

maximisation of blood

production.

The Unit is one of four

which the NIHR funded in

September 2015 and col-

laborators include the

Universities of Warwick,

Bath and the West of

England, along with sever-

al industrial partners.

Bristol Biobank

Page 10 Bristol CardioVascular Newsletter

Researchers may re-

quest to deposit sam-

ples into the Biobank

following the end of a

NHS Research Ethics

Committee approved

study. Consent must

have been taken using

study specific docu-

mentation for the

storage and use of

these samples in re-

search beyond the

study. The team will

also be happy to re-

ceive applications to

deposit samples for

specific projects you

wish to set-up using

Biobank permissions

and documentation.

The new Bristol Bi-

obank, funded by the

David Telling Charita-

ble Trust with stake-

holders from the Uni-

versity of Bristol and

University Hospitals

NHS Foundation Trust,

stores samples collect-

ed from patients and

healthy volunteers for

use in biomedical re-

search. The samples

form a biorepository

to which researchers

can apply for use in

their research. The

collection of a wide

range of samples will

provide a platform for

research into complex

conditions.

The Bristol Biobank is

licensed by the Human

Tissue Author i ty

(licence 12512) to

store human tissue

for research and has

ethics approval from

Wales Research Ethics

Committee 3 as a re-

search tissue bank to

collect and issue bio-

materials for biomedi-

cal research across a

range of therapeutic

areas. If you are inter-

ested in finding out

more about the op-

portunities of working

with the Biobank

please contact Manag-

er Claire Matthews.

The Wellcome Trust new Strategic Framework

Wellcome’s new framework consists of three complementary approaches across

science, research and engagement with society:

1. Advancing Ideas. Wellcome will continue to respond to great ideas and inspired thinking that

address the fundamental health challenges of our time.

2. Seizing opportunities. Wellcome brings ideas together to make a big difference, providing in-

tensive support that creates real change. They identify times when concerted intervention can

accelerate progress towards better health. Priorities will evolve as new challenges arise, draw-

ing on insights from a rich history of achievement and a network of experts from different dis-

ciplines around the world. Initial priorities include Science education.

3. Driving reform. Wellcome changes ways of working so more ideas can flourish, leading by ex-

ample and campaigning for wider reform. Their record in areas like open access to research

results, public engagement, and research careers has earned us the credibility to challenge

ways of working, and to propose better alternatives. One area on which reform will concen-

trate is Science to health- insights most improve health when they are applied to diagnosis,

prevention and therapy. They will work to improve intellectual property and translation sys-

tems so business and academia are encouraged to innovate for better health.

New BHF Research Strategy 2015-2020

The objectives of their research strategy are:

1) To understand the social, genetic, cellular and molecular causes of CV disease

2) To discover better ways of preventing, diagnosing and treating CV disease

3) To enhance translation of these research discoveries into better patient care

They remain committed to supporting researchers at all stages of their career, to funding re-

search into all forms of CV disease (and associated conditions that significantly increase the risk

of CV disease, e.g. diabetes, chronic kidney disease), and to their response-mode approach.

Planned changes for the next 5 years include:

A. Targeting unmet needs. BHF will encourage informaticians to apply for their fellow-

ships; establish new funding schemes to fund nurses and allied health care professionals

undertaking research in hospitals to improve the day to day care of their patients; en-

courage and sustain research activity in cardiovascular surgery and congenital heart dis-

ease.

B. People. BHF will enhance the value and flexibility of the fellowship schemes; promote

flexible working practices in all schemes, and extend the length of the Career Re-entry

Fellowship; enable their research leaders to attract the brightest graduates from around

the world to establish their research careers in the UK as BHF-funded PhD students.

C. Partnerships. BHF will build on the success of their Centres; allow international investi-

gators to be co-applicants on BHF grants; launch BHF-Crick fellowships.

D. Translation. BHF will continue their Translational Award; facilitate a series of workshops

which will bring together discovery scientists, clinicians and industry scientists to inform

each other and identify promising avenues of translation for specific research topics.

Page 11

Researchers at Bristol can

recruit participants online

via Call For Participants, an

advertising platform focused

on bringing opportunities for

taking part in academic re-

search to the general public. A

dedicated notice board will

advertise surveys, interviews

and other research studies.

The company will also provide

support and guidance on how

to advertise research and

communicate to the public. To

post an advert go to https://

www.callforparticipants.com/

researcher.

University Policy on Open Access to research publications

Senate has approved a mandate for the institutional policy on Open Access to research

publications, and this will take effect from 1 October 2015. Academics and research

students are required to deposit, at the point of acceptance from the publisher, eligible

research outputs in the institutional repository (Pure). The mandate is to ensure that all

research outputs that will be submitted to the post-2014 REF are eligible, under new

requirements from HEFCE. Further information about the mandate and help available.

For the full policy please see the Institutional Policy web page.

Page 12

Ballooning Platelets and the Future of Anti-thrombotic Drugs

Platelets co-ordinate the

clotting process by expos-

ing phosphatidylserine (PS)

on their cell surface, al-

lowing recruitment of the

components of the clot-

ting system that lead to

the generation of a clot.

This procoagulant activity

therefore depends upon

the surface area of mem-

brane with exposed PS.

Led by Prof Alastair Poole

the study showed that this

surface area is enhanced

substantially by the for-

mation of balloon struc-

tures from platelets, with

subsequent procoagulant-

spreading of platelets over

the adherent surface.

Bleeding defects may thus

be due to aberrant pro-

coagulant membrane dy-

namics as exemplified by

patients with Scott syn-

drome, a disorder where

PS exposure is blocked.

Furthermore, they found

that a co-ordinated system

of salt and water entry

drives this platelet mem-

brane ballooning and pro-

coagulant-spreading – and

that the system can be

modified pharmacological-

ly.

The research could ulti-

mately lead to the develop-

ment of better blood-

thinning drugs for patients

who experience complica-

tions with or are resistant

to existing antiplatelet

drugs such as aspirin. Acet-

azolamide, used in the

treatment of glaucoma and

other conditions, has ac-

tions which include the

blockade of water entry

into cells. It was shown

than acetazolamide not

only substantially impaired

ballooning and thrombin

generation in the test tube,

but also markedly reduced

thrombus formation in vivo.

Drugs that modify water

entry into platelets may

therefore represent novel

antithrombotic therapies for

the management of coronary

artery disease and preven-

tion of stroke. The research

provides added rationale for

monitoring patient bleeding

risk when acetazolamide is

administered with anticoagu-

lants.

Agbani EO, van den Bosch

MTJ, Brown E et al. (2015).

Coordinated Membrane Bal-

looning and Procoagulant-

Spreading in Human Plate-

lets. Circulation. Published

online 1 September 2015.

Mem

bra

ne

ballo

onin

g and p

roco

agu

lant-sp

readin

g are

co-

ordin

ate

d e

vents

. SE

M im

age

of pla

tele

ts a

dher

ent

to c

olla

gen s

how

BAPS

and c

onve

ntion

al sp

read

non

-ballo

oned

phen

otyp

es

Page 13

ELIZABETH BLACKWELL FUNDING OPPORTUNITIES

EBI Workshops Funding

Support for interdisciplinary workshops in health research at a new or emerging interface

between two or more disciplines. Applications are reviewed on a rolling basis.

EBI Catalyst Fund

Pump priming awards can support the most promising and ambitious ideas across the

widest interdisciplinary boundaries. These projects will be identified largely through the

running of workshops to explore new possibilities and identify the big questions. Applica-

tions are reviewed on a rolling basis.

Returning Carers Scheme

UoB has introduced a Returning Carers’ Scheme (RCS) to support academic staff across

all faculties in re-establishing their independent research careers on return from extended

leave (16 weeks or more) for reasons connected to caring - such as maternity leave,

adoption leave, additional paternity leave, or leave to care for a dependant.

The deadline for applications is 30 April and 31 October each year.

EBI Early Career Fellowships

Designed to support exceptionally talented and motivated researchers who wish to fur-

ther their career by applying for prestigious, independent, externally-funded fellowships to

be held at Bristol. This scheme is available to internal and external applicants.

Closing date: 12 February 2016

H2020: 2016-2017 Societal Challenges and LEIT

Work Programmes published

The Societal Challenge Work Packages reflect the policy priorities of the EC and address

shared concerns across Europe. The challenge-based approach is expected to bring together

resources and knowledge across different fields, technologies and disciplines. Topic areas in-

clude Health, Food Security, Energy, Transport, Climate, Security and Inclusive, Innovative and

reflective societies. A minimum of three partners from three different EU countries are re-

quired for both Societal Challenges and LEIT proposals, with a variety of deadlines over the

next two years (starting February 2016). If you are interested in discussing involvement in one

of these calls, either as a lead or partner, or would like more details about what is available in

your area of interest please contact Tiernan Williams.

Page 14

FUNDING OPPORTUNITIES

A calendar of potential funding opportunities for cardiovascular sciences has been set up via

Research Professional. Subscribing to a calendar will place the entries in your own calendar,

which will update automatically according to pre-specified search criteria. Staff and students

have FREE access to Research Professional online from all computers on the University net-

work. You can create your own personalised funding opportunity e-mail alerts by registering

with RP. Find out all about it on the RED website.

Medical Research Council: Highlight Notice

Neurovascular Ageing

Closing date and award amount depend on scheme applied for

Vascular ageing and neurodegenerative diseases are two of the leading health challenges

faced by our society, yet there are significant knowledge gaps in current understanding of

the biology of ageing as it relates to the central nervous system (CNS), particularly about

the interplay between the vasculature and neuronal systems at the mechanistic lev-

el. Through this highlight notice applicants are invited to submit innovative research pro-

Page 15

posals that address opportunities under this theme in the following areas:

Knowledge expansion– biological factors

Tools and technology

Capacity building

British Heart Foundation

Strategic appointment grants

Closing Date: none Award amount: £3M

Aim to help universities recruit a high-calibre overseas scientist for a BHF chair. Full applica-

tions will not be considered without prior approval to submit. The award is intended to cover

the professor’s salary and that of their immediate support staff as well as a programme of re-

search for five years.

British Heart Foundation

Immediate postdoctoral basic science research fellowship

Closing Date: none Award amount: unspecified

Enable newly qualified postdoctoral researchers to make an early start in developing their inde-

pendent cardiovascular research careers. Candidates should be in the final year of their PhD

studies or have no more than one year of postdoctoral research experience from the date of

their PhD viva. The fellowship should not be held in the institution where the PhD was carried

out. The fellowship is awarded for a duration of three years with the possibility of a one-year

extension. The award may include the applicant’s salary, research consumables and small items

of equipment. The foundation encourages fellows to spend up to 18 months overseas or at a

second UK institution. The award may also include travel costs, subsistence and contributions

to healthcare insurance.

British Heart Foundation

Strategic capital grants

Closing Date: none Award amount: unspecified

Support major research institutions with large capital needs for their cardiovascular research

strategy. Applications will not be considered without prior approval to submit. It is unlikely that more than one such award will be made to any institution in a five-year period.

British Heart Foundation

Advanced training awards

Closing Date: none Award amount: £30,000

Enable researchers to retrain and gain additional expertise in an established research institution

in the UK. Researchers must be moving into a different field of science, for example from cell

biology to bioinformatics or entering cardiovascular science from a different discipline. Applica-

tions may include basic or applied clinical research relevant to the cardiovascular system. Col-

laborative research between clinicians and basic scientists is encouraged.

British Heart Foundation

Clinical research training fellowships

Closing Date: none Award amount: £10,000

Enable medically qualified graduates to undertake research training in established research insti-

tutions in the UK. The primary supervisor must devote at least 10 per cent of their time to su-

pervising the student, and a second supervisor should also be identified. Students should have

completed foundation year 2, but should not yet have obtained their certificate of completion

of training. Fellowships may last two or three years to allow for the completion of either a PhD

or an MD or equivalent.

British Heart Foundation

Translational awards

Closing Date: none Award amount: £250,000

This award will help to bridge the funding gap between promising innovations and the clinic

with the aim of accelerating advances in cardiovascular science for patient benefit. Proposed

technologies may include therapeutics; devices; diagnostics; imaging technologies; algorithms

and computer modelling.

British Heart Foundation

Clinical research leave fellowships

Closing Date: none Award amount: unspecified

Enable NHS staff to undertake dedicated PAs in research in a recognised UK centre of excel-

lence in cardiovascular medicine. Clinical studies may also be supported. NHS consultants with

recent research records may apply. Awards may be for up to one year full time or up to three

years part time. They include reimbursement of reasonable costs to cover relinquished PAs,

and research consumables.

British Heart Foundation

Project grants

Closing Date: none Award amount: £299,999

Support short-term research projects lasting up to three years. Grants may cover salaries, re-

search consumables and equipment.

Page 16 Bristol CardioVascular Newsletter

Page 17

Vascular Anaesthesia Society of Great Britain and Ireland

Departmental awards

Closing Date: none Award amount: £10,000

Support research and audit projects in the field of vascular anaesthesia undertaken by anaes-

thetic trainees. The purpose is to advance both the care of patients undergoing vascular proce-

dures and the training and development of the vascular anaesthetics of the future. The lead ap-

plicant must be a member of the VASGBI and hold a substantive consultant or equivalent. The

research project must be undertaken by trainees and fellows not holding a substantive or lo-

cum consultant post.

University of Bristol

University Research Fellowships

Closing date: 12-Feb-16 Award amount: not specified

Enable academic staff to carry out a dedicated research project lasting twelve months.

National Institute on Aging

Diabetes and cardiovascular disease in older adults (R21)

Closing date: 16-Feb-16 Award amount: US$275,000

Encourage basic, clinical and epidemiological outcomes research on the impact of age on the

development of, diagnosis and management of diabetes and cardiovascular disease complica-

tions in older persons or animal models. Research supported by this initiative is expected to

elucidate the role of ageing mechanisms that underlie the increased vulnerability of older adults

to DM and its CVD complications and to provide evidence-based guidance to improve more

appropriate diagnostic criteria, risk stratification and intervention recommendations to prevent

the onset, or improve short- and long-term outcomes, of DM and CVD in older persons.

National Heart, Lung and Blood Institute

Secondary dataset analyses in heart, lung and blood diseases and sleep disorders (R21)

Closing date: 19-Feb-16 Award amount: US$150,000

To stimulate well-focused secondary analyses of existing human datasets to test innovative hy-

potheses concerning the epidemiology, pathophysiology, prevention or treatment of diseases

and conditions relevant to the NHLBI’s mission. Analysing existing datasets in novel ways pro-

vides a cost-effective method to address research questions and generate preliminary data for

subsequent research proposals.

European Society of Cardiology

Research grants

Closing date: 28-Feb-16 Award amount: €25,000

Enable candidates to undertake specialised research or further training in the cardiovascular

field in an European Society of Cardiology regular member country other than their own. The

goal is to help young candidates to obtain research experience in a high standard academic cen-

tre. Applicants should be below 36 years of age and be citizens or permanent residents of an

ESC member or affiliated member country.

European Society of Cardiology

Training grants

Closing date: 28-Feb-16 Award amount: €25,000

Enable young cardiologists to undertake clinical training in an ESC regular member country oth-

er than their own. The aim is to help young candidates attain clinical competence and acquire

experience of high-quality cardiological practice which will enable them to contribute to im-

proving academic standards on return to heir own country.

European Society of Cardiology

Early career training grant

Closing date: 28-Feb-16 Award amount: €25,000

Enables medical graduates to learn an innovative method or technique and be familiar with the

organisation and work of an internationally recognised research group in an ESC regular mem-

ber country other than their own. The goal of this award is to help young candidates attain clin-

ical competence and acquire experience of high quality cardiological practice which will enable

them to contribute to improving academic standards on return to their own country.

Applicants must be physicians in cardiology with less than two years of training.

Newton Fund

Mobility Grants / Research Collaboration Programme

Closing date: 2-Mar-16 Award amount: unspecified

Eligible partner countries: Brazil, Malaysia, Mexico, South Africa, Thailand (BA, RS), Turkey.

These grants provide support for international researchers based in a country covered by the

Newton Fund to establish and develop collaboration with UK researchers around a specific

jointly defined research project. These one-year awards are particularly suited to initiate new

Page 18 Bristol CardioVascular Newsletter

Page 19

collaborative partnerships, between scholars who have not previously worked together, or new

initiatives between scholars who have collaborated in the past.

The grants intend to strengthen the research capacity/capability of, and contribute to promot-

ing economic development and social welfare in, the overseas country. The awards will also

initiate the development of longer-term links between the overseas and UK researchers

NIHR CLAHRC West

Implementation projects and research proposals

Closing date: 07-Mar-16 Award amount:

Funds will go towards projects that address two key issues: (a) Integrated working across the

health system; (b) Effective and efficient optimal care

NIHR

Programme development grants

Closing date: 8-Mar-16 Award amount: £100,000

Aim to produce independent research findings that will have practical application for the benefit

of patients and the NHS in the relatively near future. This is a complementary scheme to allow

investigators to undertake preparatory research that will position them to submit a competitive

Programme Grant application.

ERA-CVD

Transnational research projects on cardiovascular diseases

Closing Date: 08-Mar-16 Award amount: unspecified

Aims to develop translational innovative projects for diagnosis and therapy of heart failure. Re-

search should focus on the association between precipitating or causative factors and the mo-

lecular effectors and organ dysfunction in the development and progression of heart failure

with reduced ejection fraction and heart failure with preserved ejection fraction. Proposals

must cover at least one of the following themes: earlier recognition and prognosis of heart fail-

ure; innovative approaches to prevent and treat heart failure or to reverse the remodelling

process; role of the interface between myocardium and non-myocyte cells in pathophysiology

of heart failure.

The participation of young investigators is strongly encouraged. Consortia must involve at least

three and a maximum of five partners from at least three countries participating in the call.

McGill University

Louis and Artur Lucian Award

Closing date: 18-Mar-16 Award amount: CDN$60,000

Designed to honour outstanding research in the field of circulatory diseases by a scientific inves-

tigator(s) whose contribution to knowledge in the field is deemed worthy of special recognition.

It is hoped that through this Award, collaborative research in the field of circulatory diseases

can be established between McGill and research centres elsewhere.

The successful recipient is invited to spend a minimum of a one- to two-week period of time at

McGill University to give a formal Lucian Lecture, to have interchanges with members of the

McGill community, and possibly to undertake a research collaboration with McGill investigators

in the field of circulatory diseases. Prospective recipients should be nominated.

Institute for Advanced Studies

Enhances research and intellectual life at the University of Bristol by funding workshops and fel-

lowships in pursuit of new ideas. They offer resources and opportunities to develop novel areas

of research through funding for workshops (including virtual seminars) and for visits by experts

and colleagues from abroad through the IAS Benjamin Meaker Visiting Professorships scheme.

Application Deadlines:

Benjamin Meaker Visiting Professorships: 31-Mar-16 (May to August 2016), 26-Feb-

16 (medium-term)

University Research Fellowships: 12-Feb-16 (for University Research Fellow-

ships, University Senior Research Fellowships, IAS Research Fellowships and Translational

Neuroscience Research Fellowships)

Bayer

Grants4Targets

Closing Date: 31-Mar-16 Award amount: €125,000

Aims to encourage research on novel targets and disease-related biomarkers in the fields of

cardiology, hematology and ophthalmology. The following different types of grants, depending

on the specifics of the target and its development phase will be awarded:

•support grants worth between €5,000 and €10,000 to advance research on targets that are at

a very early stage of discovery;

•focus grants worth between €10,000 and €125,000 for more mature ideas, such as addressing

specific aspects of a target as a first step towards transferring it to the drug discovery process.

Page 20 Bristol CardioVascular Newsletter

Page 21

European Foundation for the Study of Diabetes

European research programme in microvascular complications of diabetes

Closing Date: 01-Apr-16 Award amount: €300,000

Aims to stimulate and accelerate European basic and clinical research focusing on microvascu-

lar complications of diabetes. Projects involving clinical trials will not be considered. Grants are

worth up to €100,000 for basic research projects and up to €300,000 for clinical research pro-

jects. Clinical research projects must have a maximum duration of three years.

Department of Health

Health services and delivery research programme – researcher-led workstream

Closing Date: 14-Apr-16 Award amount: unspecified

Supports research into the quality, effectiveness and accessibility of health services, including

evaluations of how the NHS might improve delivery of services. For this round, proposals

around the organisation and quality of care in the last year are encouraged.

This includes research to identify cost-effective models of specialist palliative care and evalua-

tion of other promising service innovations to provide joined up, person centred care to those

at the end of life. Applicants may submit either a standard outline proposal or an evidence syn-

thesis full proposal. The workstream has a continued interest in research areas including: surgi-

cal and implantable devices; primary care interventions; very rare diseases; long-term condi-

tions in children.

NIHR will fund HEIs at a maximum of 80 per cent of fEC except for equipment worth over

£50,000.

Above and Beyond and University Hospitals Bristol

Research Capability Funding

Closing date: 26-Apr-16 Award amount: £20,000

Aim to promote high quality biomedical research in UH Bristol. Applications are welcomed

from any medical or non-medical UH Bristol employee, or university academic (Universities of

Bristol and the West of England) holding an honorary contract with UH Bristol. Funds can be

used to: Fund Research Sessions/PAs (for medical and non-medical staff) to allow time to prepare

NIHR research grant applications; Fund the generation of preliminary or underpinning data to support an NIHR application

(pump-priming)

Page 22 Bristol CardioVascular Newsletter

British Council

BIRAX regenerative medicine initiative

Closing Date: 12-May-16 Award amount: £400,000

Enables scientists in both the UK and Israel to carry out collaborative research which furthers

advances in the field of regenerative medicine. The scheme funds research that: explores the

use of stem cell technology and tissue engineering in the context of fundamental disease pro-

cesses; discovers new mechanisms that might be targeted to develop novel therapeutic applica-

tions of regenerative medicine; advances understanding of stem cell biology, using lessons learnt

from developing tissues and organs, or the mechanisms underlying cell fate and the principles of

cellular pluripotency for the development of stem cell-based therapies; advances cell and gene

therapies.

Medical Research Council

New investigator research grants – population and systems medicine

Closing date: 25-May-16 Award amount: unspecified

Provide support for clinical and non-clinical researchers while they are establishing themselves

as independent principal investigators. For those who already have an institutional post, it pro-

vides funding and protected time with which to establish an independent research career. The

grant is also a potential source of research funding for fellows whose awards only cover a per-

sonal salary or limited research funds. Applicants must hold a PhD, DPhil or an MD, have between three and 10 years postdoctoral

research experience and should be in their first lecturer appointment, hold a junior fellowship

or be in a senior postdoctoral position.

Medical Research Council

Programme grants – population and systems medicine

Closing date: 25-May-16 Award amount: unspecified

Provide large and long-term renewable funding. A programme is defined as a coordinated and

coherent group of related projects that may be developed to address an interrelated set of

questions across a broad scientific area. The expectation is that not all questions will necessarily

be answered within the tenure of the award. Parts of the programme may be continuations of

current activity, but other elements should be innovative and ambitious.

Royal Society of Medicine

Venous pump-priming grant

Closing date: 25-May-16 Award amount: unspecified

Supports research that benefits the phlebology and endovenous fields. Trainee specialists under

40 years of age at the time of application may apply.

Page 23

European Society for Vascular Surgery

Research grants

Closing Date: 31-May-16 Award amount: unspecified

Enable young European vascular surgeons to conduct research projects. Applicants must be

European, trainee members or full members of the society and no more than 40 years of age.

Heart Research UK

Translational research project grants

Closing date: 1-Jun-16 Award amount: £150,000

Aim to support research which can improve the health and treatment of patients with cardio-

vascular disease by advancing current practice or enabling innovative discoveries to be efficient-

ly transferred into practical tools to prevent, diagnose and treat human disease.

European Society of Cardiology

Great grant for thrombosis researchers

Closing Date: 15-Jun-16 Award amount: €12,000

Enables young scientists, aged 35 years or under, to gain training in basic research techniques in

the field of atherothrombosis at well-known high quality research laboratories.

Heart Research UK

Novel and emerging technology grant

Closing date: 01-Oct-16 Award amount: £250,000

Supports research on novel and emerging technologies and new applications of existing tech-

nologies to diagnose, treat and prevent heart disease and related conditions. The grant may

support approaches including tissue and bioengineering, development and evaluation of new

diagnostic and therapeutic devices, bioimaging, nanotechnology, biomaterials, genomic and pro-

teomic approaches, computational biology and bioinformatics. Emerging technologies or strate-gies in the management of risk factors, the evaluation of invasive cardiology procedures, the

evaluation of new surgical approaches to cardiovascular disease, strategies aimed at improving

the efficacy of ventricular assist and other devices, and the outcome of resuscitation after cardi-

ac arrest may also be supported.

Page 24 Bristol CardioVascular Newsletter

THIS ISSUE’S SHOWCASED PUBLICATION

Scatteia A, Pagano C, Pascale C, Guarini P, Marotta G, Perrone-Filardi P, Bucciarelli-Ducci C

and Dellegrottaglie S (2016). Asymmetric hypertrophic cardiomyopathy in generalized lipo-

dystrophy. International Journal of Cardiology. 202, pp724-725

Lipodystrophies are a rare group of diseases characterised by generalised or partial lipoatrophy.

They can be due to genetic or acquired causes and the loss of adipose tissue leads to severe

metabolic alterations such as insulin resistance, low leptin levels with increased appetite, hyper-triglyceridemia, and fat deposits in lymphoreticular tissues. Many cardiac abnormalities have

been described as part of congenital generalised lipodystrophy, but the most frequent of them is

symmetric hypertrophic cardiomyopathy. Additional cardiac abnormalities described in the lit-

erature are marked autonomic dysfunction and dilated cardiomyopathy with severe heart fail-

ure. The etiology of the cardiomyopathies remains unclear in this condition. From a theoretical

standpoint, the severe insulin resistance observed in these patients may prompt cardiomyocyte

hypertrophy by activating IGF-1 receptors, which are largely expressed in the myocardial tissue

and stimulate cell growth. A magnetic resonance spectroscopy and imaging study found that

myocardial triglyceride content was elevated in hypertrophied cardiomyocytes of patients af-

fected by generalized lipodystrophy. Theoretically, these findings suggest that triglyceride de-

posit might cause a “lipotoxic cardiomyopathy”, as exceeding lipids are shunted into non-

oxidative pathways with the accumulation of toxic lipid species. This may alter, in turn, cellular

signalling, promoting mitochondrial dysfunction and increased cell apoptosis. Asymmetric hyper-

trophy has been rarely reported in young patients with lipodystrophy, possibly as a conse-

quence of the hyperinsulinemia-induced overgrowth of an otherwise healthy heart. In the case

with asymmetric hypertrophic cardiomyopathy presented here, pre-contrast dark blood images

ruled out the presence of edema and/or fatty infiltration while myocardial fibrosis/necrosis was

found. This is a highly intriguing finding, as asymmetric hypertrophy with late gadolinium en-

hancement involving the hypertrophied segments is a typical feature of sarcomeric hypertrophic

cardiomyopathies and has been linked to

adverse prognosis. Our findings might

help in shedding new light on the yet

mysterious pathophysiology of cardiac

involvement in lypodystrophies. This is

important even more, as cardiac in-

volvement in lipodystrophy is consid-

ered to be associated with poor prog-

nosis.

Pre-contrast dark blood images with STIR T2-

weighted (A.) and FSE T1-weighted technique

(B.), both showing a hypointense area (arrow) in

the hypertrophic anterior/antero-septal region

excluding, respectively, the presence of fatty

infiltration or edema. Late post-contrast images

in short-axis view (C.) and modified 2-chamber

view (D.) showing a focal area of late gadolini-

um enhancement (arrow) involving the hyper-

trophic anterior/antero-septal region and com-

patible with myocardial fibrosis/necrosis.

Page 25

White S, Newby A & Johnson T (2016). Endothelial Erosion of Plaques as a substrate for coro-

nary thrombosis. Thrombosis & Haemostasis. Published online 21 January 2016.

Image caption: Typical features of eroded and ruptured atherosclerotic plaques. Eroded plaques contain an altered matrix

below the erosion, with more versican

and hyaluronic acid and greater num-

bers of smooth muscle cells. In addi-

tion, eroded plaques generally have

thick fibrous caps with absent or deep

seated necrotic cores and the thrombi

are less frequently occlusive. Converse-

ly, ruptured plaques have thin, frac-

tured fibrous caps with high proportion

of underlying macrophage and a large

lipid core. Ruptured plaques often show

signs of expansive remodelling.

Simmonds R, Evans J, Feder G et al. (in press). Understanding tensions and identifying clinician

agreement on improvements to early-stage chronic kidney disease monitoring in primary care:

a qualitative study. BMJ Open.

O'Callaghan E, Chauhan A, Zhao L, Lataro R, Salgado HC, Nogaret A & Paton J (in press). Util-

ity of a novel biofeedback device for within-breath modulation of heart rate in rats: a quantita-

tive comparison of vagus nerve versus right atrial pacing. Frontiers in Physiology.

Image caption: Experimental setup in which

the VN-CPG receives input from dEMG (A). A

view of the abdominal surface of the dia-

phragm shows the relative placement of two

electrodes within the costal diaphragm which

are used to record dEMG without interference

from cardiac electrical activity. The black cir-

cle within the crural diaphragm indicates the

oesophageal path. The dEMG activity is am-

plified and filtered by a pre-amplifier (black

triangle) before use as the respiratory input to

the VN-CPG. The VN-CPG is shown (bottom

right) and a simplified representation of the

differential amplifier and inhibitory interneu-

rons, N1 (blue) and N2 (red), that comprise

the VN-CPG and their respective firing pat-

terns are depicted above. Either N1 or N2

can be connected to the bipolar cuff electrode

enclosing the right cervical vagus nerve to

control HR.

Narita I, Shimada M, Yamabe H et al. (2015). NF-κB-dependent increase in tissue factor ex-

pression is responsible for hypoxic podocyte injury. Clinical and Experimental Nephrology. Pub-

lished online 29 December 2015.

RECENT PUBLICATIONS

Page 26 Bristol CardioVascular Newsletter

Dastidar AG, Rodrigues JC, Baritussio A & Bucciarelli-Ducci C (2015). MRI in the assessment

of ischaemic heart disease. Heart. 102, pp239-252

Image caption: Assessment of

chronic ischaemic heart dis-

ease: A patient with previous

anterior myocardial infarction

assessed for ischaemic heart

disease. Stress perfusion im-

aging showed basal inferior

perfusion defect (arrow), and

late enhancement imaging

showed transmural myocardi-

al infarction in the mid-distal

left anterior descending terri-

tory with viable inferior wall.

Rodrigues JCL, Amadu AM, Dastidar AG et al. (2015). Prevalence and predictors of asymmetric

hypertensive heart disease: insights from cardiac and aortic function with cardiovascular mag-

netic resonance. European Heart Journal - Cardiovascular Imaging. Published online 24 December

2015.

Wood L, Jago R, Sebire S, Zahra J & Thompson J (2015). Sedentary time among spouses: A

cross-sectional study exploring associations in sedentary time and behaviour in parents of 5

and 6 year old children. BMC Research Notes. 8, p787

Di Gregoli K, George SJ, Jackson CL, Newby

AC & Johnson JL (2015). Differential Effects of

Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2 on Atherosclerosis and Monocyte/

Macrophage Invasion. Cardiovascular Research.

Published online 8 December 2015.

Image caption: TIMP-2 deficiency induces elastin fragmenta-

tion. (A–C) Representative images of serial sections from an

atherosclerotic brachiocephalic artery with a marked elastin

fragmentation (black arrowhead in A) which have been im-

munohistochemical stained for (A) elastin van Gieson, (B)

smooth muscle cells, or (C) macrophages from a TIMP-2−/−

Apoe−/− mouse. (D) Quantification of the number of TIMP-

2+/+ Apoe−/− and TIMP-2−/− Apoe−/− mice without (black

bars) or with (red bars) elastin breaks (*P < 0.05; n = 27/28

per group; data expressed as mean ± SEM). Scale bar in A represents 100 µm and is applicable to all panels.

Page 27

Zakkar M, Angelini GD & Emanueli C (2016). Regulation of Vascular Endothelium Inflammatory

Signalling by Shear Stress. Current Vascular Pharmacology. 14.

Linneberg A, Jacobsen RK, Skaaby T et al. (2015). Effect of Smoking on Blood Pressure and

Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

Circulation: Cardiovascular Genetics. 8(6), pp832-841

Munasinghe PE, Riu F, Dixit P et al. (2015). Data supporting the activation of autophagy genes

in the diabetic heart. Data in Brief. 5, pp269-75

Mastenbroek TG, Feijge MAH, Kremers RMW et al. (2015). Platelet-Associated Matrix Metal-

loproteinases Regulate Thrombus Formation and Exert Local Collagenolytic Activity

Arteriosclerosis, Thrombosis and Vascular Biology. 35, 12, p. 2554-61

Image caption: Thrombi de-

grade underlying collagen fibers

in a time-dependent manner.

Human whole blood was per-

fused over immobilized Horm

collagen at a shear rate of

1000/s for 4 minutes. Formed

thrombi were rinsed and incu-

bated in HEPES buffer contain-

ing 2-MeSADP. At indicated

time points, thrombi were fixed

and prepared for SEM. A, Rep-

resentative SEM pictures of

Horm collagen coating before

thrombus formation and of

formed thrombi on collagen at

T=0, 2, 4, 7, and 17 hours. B,

Insets of indicated squares in A.

Arrows indicate partly degraded

collagen fibers. Representative

SEM images of 9 experiments

are depicted. Scale bar=10

μm.

Rogers C, Bryan AJ, Nash R et al. (2015). Propofol cardioplegia: A single-center, placebo-

controlled, randomized controlled trial. Journal of Thoracic and Cardiovascular Surgery. 150

(6), pp1610-1619

Kimura-Wozniak T, Duggirala A, Smith M, White S, Sala-Newby G, Newby A & Bond M

(2016). The hippo pathway mediates inhibition of vascular smooth muscle cell proliferation by

cAMP. Journal of Molecular and Cellular Cardiology. 90, pp1-10

Nguyen BAV, Fiorentino F, Reeves BC, Baig K, Athanasiou T, Anderson JR, Haskard

Page 28 Bristol CardioVascular Newsletter

DO, Angelini GD & Evans PC (2015). Mini Bypass and Proinflammatory Leukocyte Activation:

A Randomized Controlled Trial. The Annals of Thoracic Surgery. Published online 18 November

2015.

Macdonald-Wallis C, Silverwood RJ, De Stavola BL, Inskip H, Cooper C, Godfrey KM, Crozier SR, Fraser A, Nelson SM, Lawlor D & Tilling K (2015). Antenatal blood pressure for prediction

of preeclampsia, preterm birth and small-for-gestational age: Development and validation in

two general population cohorts. British Medical Journal. 351(h5948), pp1-11

Zhang H, Cannell M, Kim SJ, Watson J, Norman R, Calaghan S, Orchard C & James A (2015).

Cellular hypertrophy and increased susceptibility to spontaneous calcium-release of rat left

atrial myocytes due to elevated afterload. PLoS ONE. Published online 29 December 2015.

Patel N, Avlontis V, Jones H, Reeves B, Sterne J & Murphy G (2015). Indications for red blood

cell transfusion in cardiac surgery: a systematic review and meta-analysis. The Lancet Haematolo-

gy. 2(12), ppe543-e553

Lyon CA, Wadey KS & George SJ (2015). Soluble N-cadherin: A novel inhibitor of VSMC pro-

liferation and intimal thickening. Current Vascular Pharmacology. Published online 14 November

2015. (see image below)

Gadeberg H, Bryant S, James A & Orchard C (2015). Altered Na/Ca exchange distribution and

activity in ventricular myocytes from failing hearts. Heart and Circulatory Physiology. 310(2),

ppH262-H268

Kumar PA, Welsh GI, Raghu G, Menon RK, Saleem MA & Reddy GB (2016). Carboxymethyl

lysine induces EMT in podocytes through transcription factor ZEB2: Implications for podocyte

depletion and proteinuria in diabetes mellitus. Archives of Biochemistry and Biophysics. 590, pp10-

19

Page 29

Linneberg A, Jacobsen RK, Skaaby T et al. (2015). Effect of Smoking on Blood Pressure and

Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium.

Circulation: Cardiovascular Genetics. Published online 4 November 2015.

Taqatqa A, Diab KA, Stuart C, Fogg L, Ilbawi M, Awad S, Caputo M, Amin Z, Abdulla R-I, Ken-

ny D & Hijazi ZM (2015). Extended Application of the Hybrid Procedure in Neonates with Left

-Sided Obstructive Lesions in an Evolving Cardiac Program. Pediatric Cardiology. Published online 7 November 2015.

Image caption: Hybrid procedure in a patient with unbalanced atrioventricular canal defect, borderline hypoplastic left ven-

tricle and hypoplastic aortic arch: Median sternotomy was performed. Bilateral pulmonary artery bands (PAB) were placed

first (white stars) utilizing 3.5-mm Goretex tube 1-mm piece. a, b Six French sheath (black arrow) is in the main pulmonary

artery (MPA). c Initial angiography in the MPA via the sheath shows the band (white star). d 7 mm × 16 mm Formula

stent “Cook” was deployed in the ductus (S). e, f Repeat angiogram reveals good stent position (S) and bilateral PAB (white

stars)

Oliveira Sales EB, Colombari E, Abdala APS, Campos RR & Paton JFR (2015). Sympathetic over activity occurs before hypertension in the two-kidney one clip model. Experimental Physiology.

Published online 14 December 2015.

Baritussio A, Ghosh Dastidar A & Bucciarelli-Ducci C (2015). Cardiac MRI in a young man

Page 30 Bristol CardioVascular Newsletter

with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC). Heart. 101(21),

p1703

Choisy SC, Cheng H, Orchard CH, James AF & Hancox JC (2015). Electrophysiological proper-

ties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca

exchange. Physiological reports. 3(e12633)

Iacobazzi D, Suleiman MS, Ghorbel M, George SJ, Caputo M & Tulloh RM (2015). Cellular and

molecular basis of RV hypertrophy in congenital heart disease. Heart. 102, pp12-17

Image caption: ROS-induced intracellular changes in cardiomyocyte. The increased intracellular ROS levels occurring in RV

pressure overload affect several cardiomyocytes functions. ROS can stimulate pro-hypertrophic pathways by targeting key

molecules in this process, such as MAPK, PKC and Src proteins. The redox-mediated activation of target transcription fac-

tors (HIF-1α, cMyc and FOXO1) might be responsible for the abnormal PKD activation, which inhibits mitochondrial oxida-

tive metabolism, leading to mitochondrial dysfunction. Sustained ROS levels cause mPTP opening and mitochondrial mem-

brane depolarisation. As a consequence, more ROS are produced and cytochrome c is release from mitochondria causing

cell apoptosis. HIF-1α activation also decreases the activity of the O2-sensitive Kv channel (Kv1.5), resulting into membrane

depolarisation and elevation of cytosolic Ca2+. The surplus of cytosolic Ca2+, in addition to the excessive Ca2+ released

from the sarcoplasmic reticulum, as a consequence ROS-mediated RyR2 channel activation and SERCA inhibition, contrib-

utes to myocytes contractile dysfunction. ROS are also responsible for the MMPs/TIMPs imbalance that drives ECM remod-

elling and fibrosis. Antioxidant compounds, like Folic acid or EUK-134, by scavenging the ROS in excess, can help restore

the impaired cardiomyocyte function. Furthermore, DCA can restore ROS production and mitochondrial membrane potential

by inhibiting PDK and thereby improving glucose oxidation. ↑ indicates increase in levels; ↓ indicates decrease in level. ROS,

reactive oxygen species; PCK, protein kinase C; MAPK, mitogen-activated protein kinase; mPTP, mitochondrial permeability

transition pore; PDK, pyruvate dehydrogenase kinase; HIF, hypoxia-inducible factor; FOXO1, Forkhead box protein O1;

cMyc, v-myc avin myelocytomastosis viral oncogene homologue; RyR2, ryanodine receptor 2; Kv 1.5, potassium voltage

channel; SR, sarcoplasmic reticulum; SERCA, sarcoplasmic reticulum Ca2+-ATPase; MMP, matrix metalloproteinases; TIMP,

tissue inhibitor metalloproteinases; ECM, extracellular matrix; DCA, dichloroacetate; PKD, protein kinase D. See text for

more details.

Page 31

Anderson EL, Howe LD, Jones HE, Higgins JPT, Lawlor DA & Fraser A (2015). The Prevalence

of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and

Meta-Analysis. PloS ONE. 10(10), p. e0140908

Kourtesis I, Kasparov S, Verkade P & Teschemacher AG (2015). Ultrastructural Correlates of

Enhanced Norepinephrine and Neuropeptide Y Cotransmission in the Spontaneously Hyper-

tensive Rat Brain. ASN NEURO. 7(5), pp1-19

Abdala A, Toward M, Dutschmann M, Bissonnette J & Paton J (2015). Deficiency of GABAergic

synaptic inhibition in the Kölliker-Fuse area underlies respiratory dysrhythmia in a mouse mod-

el of Rett syndrome. The Journal of Physiology. Published online 14 December 2015.

Briant L, O'Callaghan E, Champneys A & Paton J (2015). Respiratory modulated sympathetic

activity: A putative mechanism for developing vascular resistance? Journal of Physiology.

Image caption: A, the kinetics of sympathetically mediated contraction of a smooth muscle cell (SMC) in the model. B, ex-

perimental data shows that a pre-terminal bundle (ptb) follows the vessel perivascularly. Varicose axons extend out of the

ptb in a terminating bundle (tb). These varicosities are release sites of NA onto the SMCs. The terminal bundle consist of

varicose axons, spanning a distance of 750 μm of the artery axially. SMCs are arranged circumferentially and have dimen-

sions 5 μm × 200 μm (Luff, 1996). A cylindrical layer of SMCs was therefore modelled, represented on a 2D grid (C). The

coordinates are now polar (θ,z). The modelled artery wall was endowed with 100 varicosities to fit data from the release

Page 32 Bristol CardioVascular Newsletter

probability from sympathetic varicosities. Each of the 100 varicosities is considered to be driven by the same membrane

potential pattern, as recorded from the axon of a model of a sympathetic postganglionic neurone. The arterial radius is

determined by considering each ring of SMCs; a particular circumferential ring of SMCs (z = constant; shaded area), with 3

varicosities releasing NA (noradrenaline) onto them, can be seen. Release of NA causes the SMCs to contract, changing

their length (D). The sum of these contracted lengths gives the contracted circumference (and therefore radius). SMCs are

not coupled mechanically, electrically or chemically.

Fontana M, Pica S, Reant P et al. (2015). Prognostic Value of Late Gadolinium Enhancement

Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation: Cardiovascular Genet-

ics. 132(16), pp1570-1579

Maslov L, Khaliulin I, Zhang Y, Krylatov A, Naryzhnaya N, Mechoulam R, De Petrocellis L &

Downey J (2015). Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid

Receptor Agonists. Journal of Cardiovascular Pharmacology and Therapeutics. Published online 19

October 2015.

Image caption: Proposed signaling scheme for

the cardioprotective effect of cannabinoids. CB

indicates cannabinoid receptor; AC, adenylyl

cyclase; NCX, Na+/Ca2+ exchanger; TNFR,

tumor necrosis factor receptor; mitoKATP, mito-

chondrial ATP-sensitive K+ channel; PKC, protein

kinase C; ROS, reactive oxygen species, p38

MAPK, p38 MAP kinase; MEK1/2, mitogen-

activated protein kinase; ERK1/2, extracellular

signal-regulated kinase; PI3K, phosphatidylinosi-

tol 3-kinase; PDK1/2, 3’-phosphoinositide-

dependent kinase-1/2; Akt, kinase isolated from

AKR thymoma cell line; hsp72, heat shock pro-

tein; eNOS, endothelial NO-synthase; NO, nitric

oxide; GC, guanylyl cyclase; cGMP, cyclic guano-

sine monophosphate; PKG, protein kinase G;

MKK3/6, mitogen-activated protein kinase 3

and 6; mitoPTP, mitochondrial permeability tran-

sition pore.

Chen G-F, Sudhahar V, Youn S-W et al. (2015). Copper Transport Protein Antioxidant-1 Pro-

motes Inflammatory Neovascularization via Chaperone and Transcription Factor Function. Sci-

entific Reports. 5(14780)

UK10K Consortium, Min JL, Timpson NJ et al. (2015). The UK10K project identifies rare vari-

ants in health and disease. Nature. 526(7571), pp82-90

CONTACTS

Bristol CardioVascular is run by a Steering Group:

Chair: Robert Tulloh

Consultant Paediatric Cardiologist and

Honorary Professor of Clinical Sciences

Dr Chiara Bucciarelli-Ducci Imaging

Dr Carmen Coxon Early Career Representative

Professor Costanza Emanueli Cardiovascular Regeneration

Professor Sarah George Cardiovascular Singalling

Dr Emma Hart Autonomic Regulation & Dysfunction

Dr Andrews James Cardiac Biology

Dr Thomas Johnson Cardiology

Dr Stuart Mundell Vascular Biology and atherothrombosis

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Professor Saadeh Suleiman Cardiac Biology

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e: bcv-info@bristol.ac.uk

t: 0117-931-7610

w: www.bristol.ac.uk/cardiovascular/

Bristol CardioVascular