doi: 10.1161/CIRCULATIONAHA.105.591768
(Circulation. 2006;113:1344-1352.)
© 2006 American Heart Association, Inc.
Valvular Heart Disease |
Human Semilunar Cardiac Valve Remodeling by Activated Cells From Fetus to Adult
Implications for Postnatal Adaptation, Pathology, and Tissue Engineering
From the Department of Pathology (E.A., M.F., K.M., R.F.P., F.J.S.) and Cardiovascular Division, Department of Medicine (M.A.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Departments of Emergency Medicine and Anesthesiology (P.W.), University of Massachusetts Medical School, Worcester, Mass; and Center for Molecular Imaging Research (E.A.), Massachusetts General Hospital, Boston, Mass.
Correspondence to Frederick J. Schoen, MD, PhD, Department of Pathology, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115 (e-mail fschoen{at}partners.org), or Elena Aikawa, MD, PhD, Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129 (e-mail eaikawa@partners.org).
Received September 27, 2005; revision received December 24, 2005; accepted January 9, 2006.
Background— The evolution of cell phenotypes and matrix architecture in cardiac valves during fetal maturation and postnatal adaptation through senescence remains unexplored.
Methods and Results— We hypothesized that valvular interstitial (VIC) and endothelial cell (VEC) phenotypes, critical for maintaining valve function, change throughout life in response to environmental stimuli. We performed quantitative histological assessment of 91 human semilunar valves obtained from fetuses at 14 to 19 and 20 to 39 weeks’ gestation; neonates minutes to 30 days old; children aged 2 to 16 years; and adults. A trilaminar architecture appeared by 36 weeks of gestation but remained rudimentary compared with that of adult valves. VECs expressed an activated phenotype throughout fetal development. VIC density, proliferation, and apoptosis were significantly higher in fetal than adult valves. Pulmonary and aortic fetal VICs showed an activated myofibroblast-like phenotype (
-actin expression), abundant embryonic myosin, and matrix metalloproteinase-collagenases, which indicates an immature/activated phenotype engaged in matrix remodeling versus a quiescent fibroblast-like phenotype in adults. At birth, the abrupt change from fetal to neonatal circulation was associated with a greater number of -actin–positive VICs in neonatal aortic versus pulmonary valves. Collagen content increased from early to late fetal stages but was subsequently unchanged, whereas elastin significantly increased postnatally. Collagen fiber color analysis revealed a progressive temporal decrease in thin fibers and a corresponding increase in thick fibers. Additionally, collagen fibers were more aligned in adult than fetal valves.
Conclusions— Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become quiescent, whereas collagen matures, which suggests a progressive, environmentally mediated adaptation.
Key Words: cells • collagen • remodeling • tissue engineering • valves
This article has been cited by other articles:
 |
|
 |
|
  K. Schenke-Layland, U. A. Stock, A. Nsair, J. Xie, E. Angelis, C. G. Fonseca, R. Larbig, A. Mahajan, K. Shivkumar, M. C. Fishbein, et al. Cardiomyopathy is associated with structural remodelling of heart valve extracellular matrix Eur. Heart J., September 2, 2009; 30(18): 2254 - 2265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Combs and K. E. Yutzey Heart Valve Development: Regulatory Networks in Development and Disease Circ. Res., August 28, 2009; 105(5): 408 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Dal-Bianco, E. Aikawa, J. Bischoff, J. L. Guerrero, M. D. Handschumacher, S. Sullivan, B. Johnson, J. S. Titus, Y. Iwamoto, J. Wylie-Sears, et al. Active Adaptation of the Tethered Mitral Valve: Insights Into a Compensatory Mechanism for Functional Mitral Regurgitation Circulation, July 28, 2009; 120(4): 334 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Aikawa, M. Aikawa, P. Libby, J.-L. Figueiredo, G. Rusanescu, Y. Iwamoto, D. Fukuda, R. H. Kohler, G.-P. Shi, F. A. Jaffer, et al. Arterial and Aortic Valve Calcification Abolished by Elastolytic Cathepsin S Deficiency in Chronic Renal Disease Circulation, April 7, 2009; 119(13): 1785 - 1794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sucosky, K. Balachandran, A. Elhammali, H. Jo, and A. P. Yoganathan Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4- and TGF-{beta}1-Dependent Pathway Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 254 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Balguid, A. Mol, M. A.A. van Vlimmeren, F. P.T. Baaijens, and C. V.C. Bouten Hypoxia Induces Near-Native Mechanical Properties in Engineered Heart Valve Tissue Circulation, January 20, 2009; 119(2): 290 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Schoen Evolving Concepts of Cardiac Valve Dynamics: The Continuum of Development, Functional Structure, Pathobiology, and Tissue Engineering Circulation, October 28, 2008; 118(18): 1864 - 1880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chaput, M. D. Handschumacher, F. Tournoux, L. Hua, J. L. Guerrero, G. J. Vlahakes, and R. A. Levine Mitral Leaflet Adaptation to Ventricular Remodeling: Occurrence and Adequacy in Patients With Functional Mitral Regurgitation Circulation, August 19, 2008; 118(8): 845 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Hinton Jr., C. M. Alfieri, S. A. Witt, B. J. Glascock, P. R. Khoury, D. W. Benson, and K. E. Yutzey Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2480 - H2488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Donnelly Cardiac Valvular Pathology: Comparative Pathology and Animal Models of Acquired Cardiac Valvular Diseases Toxicol Pathol, February 1, 2008; 36(2): 204 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Padera Jr. and F. J. Schoen Pathology of Cardiac Surgery Card. Surg. Adult, January 1, 2008; 3(2008): 111 - 178. [Full Text]
|
|
|
|
|
|
J. E. Mayer Tissue Engineering for Cardiac Valve Surgery Card. Surg. Adult, January 1, 2008; 3(2008): 1649 - 1656. [Full Text]
|
|
|
|
|
|
E. Aikawa, M. Nahrendorf, J.-L. Figueiredo, F. K. Swirski, T. Shtatland, R. H. Kohler, F. A. Jaffer, M. Aikawa, and R. Weissleder Osteogenesis Associates With Inflammation in Early-Stage Atherosclerosis Evaluated by Molecular Imaging In Vivo Circulation, December 11, 2007; 116(24): 2841 - 2850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Liu, V. R. Joag, and A. I. Gotlieb The Emerging Role of Valve Interstitial Cell Phenotypes in Regulating Heart Valve Pathobiology Am. J. Pathol., November 1, 2007; 171(5): 1407 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H Chester and P. M Taylor Molecular and functional characteristics of heart-valve interstitial cells Phil Trans R Soc B, August 29, 2007; 362(1484): 1437 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Aikawa, M. Nahrendorf, D. Sosnovik, V. M. Lok, F. A. Jaffer, M. Aikawa, and R. Weissleder Multimodality Molecular Imaging Identifies Proteolytic and Osteogenic Activities in Early Aortic Valve Disease Circulation, January 23, 2007; 115(3): 377 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Paruchuri, J.-H. Yang, E. Aikawa, J. M. Melero-Martin, Z. A. Khan, S. Loukogeorgakis, F. J. Schoen, and J. Bischoff Human Pulmonary Valve Progenitor Cells Exhibit Endothelial/Mesenchymal Plasticity in Response to Vascular Endothelial Growth Factor-A and Transforming Growth Factor-{beta}2 Circ. Res., October 13, 2006; 99(8): 861 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nahrendorf, F. A. Jaffer, K. A. Kelly, D. E. Sosnovik, E. Aikawa, P. Libby, and R. Weissleder Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis Circulation, October 3, 2006; 114(14): 1504 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Hinton Jr, J. Lincoln, G. H. Deutsch, H. Osinska, P. B. Manning, D. W. Benson, and K. E. Yutzey Extracellular Matrix Remodeling and Organization in Developing and Diseased Aortic Valves Circ. Res., June 9, 2006; 98(11): 1431 - 1438. [Abstract] [Full Text] [PDF]
|
|