CARDIOVASCULAR SPECIFIC GENE EXPRESSION

M

Developments in Cardiovascular Medicine

VOLUME214

The titles published in this series are listed at the end of this volume.

Cardiovascular Specific Gene Expression

edited by

PIETER A. DOEVENDANS Department of Cardiology Academic Hospital Maastricht, Maastricht, The Netherlands

ROBERTS. RENEMAN CARIM, Academic Hospital Maastricht, Maastricht, The Netherlands

and

MARC VAN BILSEN Department of Physiology Academic Hospital Maastricht, Maastricht, The Netherlands

Cardiovascular Research Institute Maastricht (CARIM) Maastricht University PO Box 616 6200 MD MAASTRICHT The Netherlands

This publication has been made possible by educational grants from the Royal Netherlands Academy of Arts and Sciences and the Netherlands Heart Foundation.

SPRINGER-SCIENCE+BUSINESS MEDIA, B.V.

A C.I.P. Catalogue record for this book is available from the Library of Congress.

ISBN 978-90-481-5189-9 ISBN 978-94-015-9321-2 (eBook) DOI 10.1007/978-94-015-9321-2

Cover pic ture by and with the courtesy of David Becker Legend to the cover picture: Transiently transfected neonatal rat cardiomyocytes assemble normal sarcomeres. Primary cultures of neonatal rat cardiomyocytes were transfected with expression plasmids harboring human beta myosin heavy chain cDNA. 1\vo days after transfection the cells were fixed and immunostained using an epitope specific antibody recognizing the human protein. The fluoro­chrome conjugated to the secondary antibody was visualized via epifluorescene and confocal microscopy.

Printed on acid-free paper

AII Rights Reserved © 1999 Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers in 1999 Softcover reprint ofthe hardcover Ist edition 1999 No partof the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical, induding photocopying, recording or by any information storage and retrieval system, without written permission from the copyright owner.

Table of Contents

List of Contributors

Preface

1. Cardiology approaching the year 2000. A clinician's look at molecular cardiology Hein].]. Wellens

Part One : Cardiovascular specific gene expression

2. The transcriptional building blocks of the heart Diego Franco, Robert Kelly, Peter Zammit, Margaret E. Buckingham and

ix

xiii

1

Antoon F.M. Moorman 7

3. A cardiac-specific troponin I promoter. Distinctive patterns of regulation in cultured fetal cardiomyocytes, adult heart and transgenic mice Stefano Schiaffino, Simonetta Ausoni, Caterina Millino, Elisa Calabria, Claudia Sandri and Raffaella Di Lisi 17

4. Mice deficient in muscle LIM protein (MLP) reveal a pathway to dilated cardiomyopathy and heart failure Pica Caroni 2 7

5. Regulation of endothelial cell specific receptor tyrosine kinase gene expression during development and disease Thorsten M. Schlaeger 35

6. Smoothelins: one gene, two proteins, three muscle cell types .... so far Guillaume ].].M. van Eys, Carlie ].M. de Vries, Sander S.M. Rensen, Victor L.].L. Thijssen, Edward L.C. Verkaar, Gisela P.G.M. Coolen, Wiel M.H. Debie, Marco C. de Ruiter and Sevilla D. Wadleigh-Detera 49

Part Two: Transcription regulation

7. Regionalization of transcriptional potential in the myocardium: 'cardiosensor' transgenic mice

vi

Robert G. Kelly, PeterS. Zammit, Diego Franco, Antoon F.M. Moorman and Margaret E. Buckingham

8. Human troponin genes: transcriptional regulation and chromosomal organization

9.

Paul].R. Barton, Pankaj K. Bhavsar, Kimberley A Dellow, Philip]. Townsend, Magdi H. Yacoub and Nigel]. Brand

Retinoid signaling: insight from genetically engineered mice Pilar Ruiz-Lozano and Kenneth R. Chien

10. Ventricular expression of the atrial regulatory myosin light chain gene Pieter A Doevendans, Ronald Bronsaer, Pilar Ruiz-Lozano,

11.

]an Melle van Dantzig and Marc van Bilsen

Expression of rat gap junction protein connexin 40 in the heart W. Antoinette Groenewegen

Part three : Ion channels and gap junction

12. Sympathetic regulation of cardiac delayed rectification: relationship to cardiac arrhythmias

67

75

87

99

117

RobertS. Kass 125

13. The sarco(endo)plasmic reticulum CaZ+ pumps in the cardiovascular system Anne-Marie Lompre, Olivier Vallot, Marielle Anger and Anne Ozog 139

14. Potassium channels; genes, proteins, and patients Connie Alshinawi and Arthur A.M. Wilde 151

15. Expression ofCx43 in cardiac and aortic muscle cells of hypertensive rats Jacques-Antoine Haefliger and Paolo Meda 161

16. Genetic engineering and cardiac ion channels Andrew A Grace, Richard C. Saumarez and]amie I. Vandenberg 171

Part four : Intracellular signaling

17. Receptor tyrosine kinase signaling in vasculogenesis and angiogenesis Thomas I. Koblizek, Werner Risau and Urban Deutsch 179

18.

19.

20.

21.

22.

Molecular analysis of vascular development and disorders Peter Carmeliet and Desire Collen Crosstalk between the estrogen receptor and the insulin-like growth factor (IGF-1) receptor. Implications for cardiac disease Christian Grohe, Rainer Meyer and Hans Vetter

Expression of basic helix-loop-helix proteins and smooth muscle phenotype in the adult rat aorta Paul R. Kemp and ]ames C. Metcalfe

Expression of the IGF system in acute and chronic ischemia Elisabeth Deindl, Rene Zimmermann and Wolfgang Schaper

Long-chain fatty acids and signal transduction in the cardiac muscle cell Marc van Bilsen, Karin A.].M. van der Lee and Ger ]. van der Vusse

Part five : DNA transfer

23.

24.

25.

26.

Index

Reduction of kidney renin expression by ribozymes Matthew G.F. Sharp, ]org Peters and]ohn]. Mullins

Receptor-dependent cell specific delivery of antisense oligonucleotides Erik A.L. Biessen and Thea ].C.van Berkel

Tissue-specific gene delivery by recombinant adenoviruses containing cardiac-specific promoters Wolfgang-Michael Franz, Thomas Rathmann, Matthias Muller, Norbert Frey and Hugo Albert Katus

Catheter-mediated delivery of recombinant adenovirus to the vessel wall to inhibit restenosis Olivier Varenne, Peter Sinnaeve, Desire Collen, Stefan P. Janssens and Robert D. Gerard

vii

193

227

237

245

257

269

285

301

319

325

ix

List of Contributors

Connie Alshinawi Academic Medical Center, University of Amsterdam, Department of Clinical and Experimental Cardiology, PO Box 22700, 1100 DE AMSTERDAM, The Netherlands.

Co-author: Arthur A.M. Wilde

Paul J.R. Barton Molecular Biology Group, Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, LONDON SW3 6LY, United Kingdom

Co-authors: Pankaj K. Bhavsar, Kimberley A. Dellow, Philip J. Townsend, Magdi H. Yacoub and Nigel J. Brand

Theo J.C. van Berkel Division ofBiopharmaceutics, LACDR, University ofLeiden, PO Box 9503, 2300 RA LEIDEN, The Netherlands

Co-author: Erik A.L. Biessen

Marc van Bilsen Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD MAASTRICHT, The Netherlands

Co-authors: Karin A.J.M. van der Lee and Ger J. van der Vusse

Peter Carmeliet Center for Transgene Technology and Gene Therapy, Campus Gasthuisberg, Herestraat 49, Universiteit Leuven, B-3000 LEUVEN, Belgium.

Co-author : Desire Collen

Pico Caroni Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 BASEL, Switzerland

Elisabeth Deindl Max-Planck-Institute for Physiological and Clinical Research, W. G. Kerckhoff­Institute, Department of Experimental Cardiology, BenekestraBe 2, D-61231 BAD NAUHEIM, Germany

Co-authors: Rene Zimmermann and Wolfgang Schaper

Pieter A. Doevendans Department of Cardiology, Cardiovascular Research Institute Maastricht, PO Box 5800, 6202 AZ MAASTRICHT, The Netherlands

Co-authors: Ronald Bronsaer, Pilar Ruiz-Lozano, Jan Melle van Dantzig and Marc van Bilsen

X

Guillaume J.J.M. van Eys Department of Molecular Biology and Genetics, University of Maastricht, P.O. Box 616,6200 MD MAASTRICHT, The Netherlands

Co-authors: Carlie J.M. de Vries, Sander S.M. Rensen, Victor L.J.L. Thijssen, Edward L.C. Verkaar, Gisela P.G.M. Coolen, Wiel M.H. Debie, Marco C. de Ruiter and Sevilla D. Wadleigh-Detera

Diego Franco Department of Anatomy and Embryology, University of Amsterdam, Spui 21, 1012 WX AMSTERDAM, The Netherlands

Co-authors: Antoon F. M. Moorman, Robert Kelly, Peter Zammit and Margaret Buckingham

Wolfgang-Michael Franz Medizinische Klinik II, Universit:it Lubeck, Ratzeburger Allee 160, D-23538 LUBECK, Germany

Co-authors : Thomas Rathmann, Matthias Muller, Norbert Frey and Hugo Albert Katus

Robert D. Gerard Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, 49 Herestraat B-3000 LEUVEN, Belgium Present address: Vector Core Laboratory and Supervisor, NGVL, Center for Gene Therapy, University of Michigan, 1150 West Medical Center Drive, ANN ARBOR, MI 48109-0688, USA

Co-authors: Olivier Varenne, Peter Sinnaeve, Desire Collen and Stefan P. Janssens

Andrew A. Grace Department of Biochemistry, University of Cambridge, Tennis Court Road, CAMBRIDGE CB2 1QW, United Kingdom

Co-authors: Richard C. Saumarez and Jamie I. Vandenberg

Christian Grohe Medizinische Univ.-Poliklinik, University of Bonn, Wilhelmstr. 3 5-3 7, D-53111 BONN, Germany

Co-authors: Rainer Meyer and Hans Vetter

W. Antoinette Groenewegen Department of Medical Physiology & Sports Medicine, Utrecht University, PO Box 80043,3508 TA UTRECHT, The Netherlands

Jacques-Antoine Haefliger Department of Internal Medicine B, University Hospital, Laboratoire de Biologic Moleculaire 19-1359, Centre Hospitalier Universitaire Vaudois, CH-1 011 LAUSANNE, Switzerland

Co-author: Paolo Meda

Robert S. Kass Department of Pharmacology, Columbia University, College of Physicians and Surgeons, 630 W. 168'h St, PH 7W, Room 318, NEW YORK, NY 10032, USA

Robert G. Kelly Department of Molecular Biology, Pasteur Institute, 28 Rue du Dr Roux, F-75724 PARIS Cedex 15, France

Co-authors: PeterS. Zammit, Diego Franco, Antoon F.M. Moorman and Margaret E. Buckingham

Paul R. Kemp Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Tennis Court Road, CAMBRIDGE, CB2 1QW, United Kingdom

Co-author: James C. Metcalfe

Thomas I. Koblizek Department of Molecular Cell Biology, Max-Planck-Institute for Physiological and Clinical Research, Kerckhofflnstitute, Parkstr. 1, D-61231 BAD NAUHEIM, Germany

xi

Present address: New York University Medical Center, Department of Pharmacology, 550 First Avenue, NEW YORK, NY 10016, USA

Co-authors: Werner Risau and Urban Deutsch

Anne-Marie Lompre CNRS ERS 570, Groupe "Genes et Proteines Musculaires", Universite Paris-Sud, Bat. 433- F-91405, ORSAY, France

Co-authors: Olivier Vallot, Marielle Anger and Anne Ozog

Robert S. Reneman Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD MAASTRICHT, The Netherlands

Pilar Ruiz-Lozano Department of Medicine, School of Medicine, University of California, 0613 Basic Science Building, LA JOLLA, CA 92093-0613, USA

Co-author: Kenneth R. Chien

Matthew G. F. Sharp Centre for Genome Research, King's Buildings, University of Edinburgh, West Mains

Road, EDINBURGH EH9 3JQ, United Kingdom Co-authors: ]Org Peters and John J. Mullins

xii

Stefano Schiaffino Department of Biomedical Sciences, CNR Center of Muscle Biology and Physiopathology, University of Padova, Viale G. Colombo 3, 1-35121 PADOV A, Italy

Co-autlwrs: Simonetta Ausoni, Caterina Millino, Elisa Calabria, Claudia Sandri and Raffaella Di Lisi

Thorsten M. Schlaeger Max Planck-Institut fUr Physiologische und Klinische Forschung, Kerckhoff-lnstitut, ParkstraBe 1, D-61231 BAD NAUHEIM, Germany

Hein J.J. Wellens Department of Cardiology, Cardiovascular Research Institute Maastricht, PO Box 5800, 6202 AZ MAASTRICHT, The Netherlands

xiii

Preface

Improving our insights into the genetic predisposition to cardiovascular disease is one of the most important challenges in our field in the next millennium, not only to unravel the cause of disease but also to improve the selection of patients for particular treatments. Nowadays, for example, subjects with a cholesterol above a particular plasma level are exposed to a cholesterol lowering regime based upon the beneficial outcome of epidemiological studies which include subjects not prone to the disease, despite a plasma cholesterol above the accepted level. Identification of the patients who are genetically predisposed to the consequences of this disorder will reduce the number of subjects unnecessarily treated and, hence, the costs of health care. Because in most cardiovascular diseases the genetic component is a consequence of more than one gene defect, only limited progress has as yet been made in identifying subjects genetically at risk. For example, in hypertension only in less than 10% of the patients the genetic defect has been identified.

It has been known for quite some time that in heart and blood vessels fetal genes are upregulated or induced when they are exposed to such disorders as high blood pressure and ischemia. Little is known about the function of these genes in the cardiac and vascular adaptation to these disorders; only guesses can be made. Therefore, it is of utmost importance to obtain more information about the specific role of these genes in fetal development and the molecular mechanisms involved in this consistently observed switch to a "fetal program" in most of the adaptation processes.

To get better insight into the genetic defects playing a role in the origin of cardiovascular diseases and into the function of the fetal genes upregulated or induced when heart and blood vessels are exposed to a changing environment, close collaboration between basic and clinical scientists is a prerequisite. Therefore, in December 1997 we brought together these scientists to discuss the expression of specific genes in the cardiovascular system. The organizers were delighted that internationally renown scientists and young investigators accepted our invitation to participate in this discussion. The book presented here is a reflection of the papers presented at the workshop. The discussions were vivid and very interesting but these are not included in the book, because to the opinion of the editors most of the chapters include the essence of the discussions held. On behalf of the editors I would like to thank the authors for their contributions, making this book a good reflection of our present knowledge of cardiovascular specific gene expression.

Without ignoring the contribution of others, it is my pleasure to thank Pieter Doevendans and Marc van Bilsen for their hard work. Without them we would not have been in a situation to look back at a fantastic scientific happening.

Robert S. Reneman