pathology of pulmonary arterial hypertension i from rubin tuder
TRANSCRIPT
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Rubin M. Tuder, M. D.
Program in Translational Lung Research
Division of Pulmonary Sciences and Critical Care
Medicine, Department of Medicine
University of Colorado, School of Medicine
PVRI
I. Pathology of pulmonary arterial
hypertension
European Cardiology Society, Nice, 2012
Pulmonary Hypertension: Future expectations
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Pulmonary vascular pathology:
importance
NormalIPAH
RCC: +ctl
CAIX
HIF-1a
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Where do pulmonary vascular lesions occur?
•Number of pulmonary
Arteries (17 orders)
10^8
Elastic (orders 17-10):
3,000
Muscular (orders 9-5):
800,000
Precapillary (orders 4-1;
25 um):
70 million
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Advancing our understanding of pulmonary
vascular pathology: going back to basics
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http://www.ipahresearch.org/
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Pulmonary hypertension breakthrough
initiative (PHBI): 2006
Transplant
centers (n=9)
Tissue Centers:
Alabama
Denver
Blood Lung
explants
Cell Processing
Centers (n=2)
Genomics
Center
Proteomics
Center
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MACRO VIEW OF RIGHT LUNG SLICES
Lung processing: sampling
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PAH
Control
Lung accrual: 2006-2011
Gender
Gender
IPAH
Clinical Dx at enrollment
FPAHCHD
CVD
Stacher et al., AJRCCM, 2012
Drug
VOD
3
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Demographics and Hemodynamics
Males
Females
Stacher et al., AJRCCM, 2012
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Vascular Quantification Method
• Step 1: a-SMA external layer
• Step 2: a-SMA internal layer
• Step 3: TM internal layer
• R = √(A/π)
Original
40x image
a-SMA
TM
DAPI
1
2
3
4
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Morphometric parameters: control vs. PAH
Stacher et al., AJRCCM, 2012
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Stacher et al., AJRCCM, 2012Control PAH
Morphometric parameters: control vs. PAH
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Morphometric parameters and pathological PAH
subphenotypes: plx lesions
ControlsControls
Stacher et al., AJRCCM, 2012
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Variability of pulmonary vascular lesions
Stacher et al.,
AJRCCM, 2012
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Plexiform lesions
Stacher et al., AJRCCM, 2012
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Histopathological patterns
IPAH- APAH- VOD-
IPAH, FPAH, HIV
Schisto, Liver DxCVD: Scleroderma,
Lupus.
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PAH patterns and lung hemodynamics
Stacher et al., AJRCCM, 2012
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Pathological patterns and pulmonary vascular
remodeling
Stacher et al., AJRCCM, 2012
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BMPRII: worse pulmonary vascular remodeling
Stacher et al., AJRCCM, 2012
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Impact of perivascular inflammation
Stacher et al.,
AJRCCM,
2012
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Impact of treatments on pulmonary vascular lesions
Lack of correlation:
Yes/No: tx and
vessel wall
(intima, media)
plexiform lesions
Stacher et al., AJRCCM, 2012
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Limitations
Sampling
Population
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Summary
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Acknowledgments
Univ. Colorado: Elvira Stacher (Univ. of Graz), Brian Graham,
James Hunt, Aneta Gandjeva, Carlyne Cool, Steve Groshong
University of Michigan (DTC): Valerie McLaughlin, Marsha
Jessep
Univ. Alabama: William Grizzle
PHBI: Transplant sites: Alleghene University of Medical Sciences (PI: Raymond L. Benza, M.D.);
Baylor College of Medicine (George Noon, M.D.); Cleveland Clinic (PI: Serpil Erzurum, M.D.);
Duke University (PI: Pang-Chieh Jerry Eu, M.D.); Stanford University-UCSF (PI:: Marlene
Rabinovitch, M.D.); University of Alabama (PI: Keith Wille, M.D.; prior PI: Raymond L. Benza,
M.D.); University of California, San Diego (PI: Patricia Thistlethwaite, M.D., Ph.D); Vanderbilt
University (Barbara Meyrick, Ph.D..
CMREF