| Extracellular matrix remodeling and cell phenotypic changes in dysplastic and hemodynamically altered semilunar human cardiac valves. | |
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MedLine Citation:
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PMID: 20817569 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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INTRODUCTION: Congenital cardiac valve disease is common, affecting ∼1% of the population, with substantial morbidity and mortality, but suboptimal treatment options. Characterization of the specific matrix and valve cell phenotypic abnormalities in these valves could lend insight into disease pathogenesis and potentially pave the way for novel therapies. METHODS: Thirty-five human aortic and pulmonic valves were categorized based on gross and microscopic assessment into control valves (n=21); dysplastic valves, all except one also displaying hemodynamic changes (HEMO/DYSP, n=6); and hemodynamically altered valves (HEMO, n=8). Immunohistochemistry was performed on valve sections and flow cytometry on valvular interstitial cells. RESULTS: While both hemodynamically altered aortic and pulmonic valves demonstrated increased collagen turnover and cell activation, prolyl 4-hydroxylase and hyaluronan increased in hemodynamically altered aortic valves but decreased in hemodynamically altered pulmonic valves relative to control valves (P<.001). HEMO/DYSP aortic valves demonstrated decreased collagen and elastic fiber synthesis and turnover compared to both hemodynamically altered aortic valves and control aortic valves (each P<.006). Valvular interstitial cells from both hemodynamically altered and HEMO/DYSP pulmonic valves showed altered cell phenotype compared to control valves (each P<.032), especially increased non-muscle myosin. Furthermore, valvular interstitial cells from hemodynamically altered pulmonic valves and HEMO/DYSP aortic and pulmonic valves each demonstrated greater size and complexity compared to control valves (each P<.05). CONCLUSIONS: Dysplastic semilunar valves displayed alterations in collagen and elastic fiber turnover that were distinct from valves similarly exposed to altered hemodynamics as well as to control valves. These results demonstrate that dysplastic valves are not simply valves with gross changes or loss of leaflet layers, but contain complex matrix and cell phenotype changes that, with future study, could potentially be targets for novel nonsurgical treatments. |
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Authors:
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Elizabeth H Stephens; Jennifer Shangkuan; Joyce J Kuo; Joshua L Carroll; Debra L Kearney; Kathleen E Carberry; Charles D Fraser; K Jane Grande-Allen |
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Publication Detail:
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Type: Journal Article Date: 2010-09-02 |
Journal Detail:
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Title: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology Volume: 20 ISSN: 1879-1336 ISO Abbreviation: Cardiovasc. Pathol. Publication Date: 2011 Sep-Oct |
Date Detail:
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Created Date: 2011-09-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9212060 Medline TA: Cardiovasc Pathol Country: United States |
Other Details:
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Languages: eng Pagination: e157-67 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Bioengineering, Rice University, Houston, TX, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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