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PMID: 19713546 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Heart valve development: regulatory networks in development and disease.

Circulation research ·Vol. 105 ·No. 5 ·2009-08-28 ·Pages 408-21

Combs MD, Yutzey KE

Abstract

In recent years, significant advances have been made in the definition of regulatory pathways that control normal and abnormal cardiac valve development. Here, we review the cellular and molecular mechanisms underlying the early development of valve progenitors and establishment of normal valve structure and function. Regulatory hierarchies consisting of a variety of signaling pathways, transcription factors, and downstream structural genes are conserved during vertebrate valvulogenesis. Complex intersecting regulatory pathways are required for endocardial cushion formation, valve progenitor cell proliferation, valve cell lineage development, and establishment of extracellular matrix compartments in the stratified valve leaflets. There is increasing evidence that the regulatory mechanisms governing normal valve development also contribute to human valve pathology. In addition, congenital valve malformations are predominant among diseased valves replaced late in life. The understanding of valve developmental mechanisms has important implications in the diagnosis and management of congenital and adult valve disease.

MeSH Terms
Animals Cell Differentiation Cell Lineage Cell Proliferation Endocardial Cushions/embryology Extracellular Matrix/metabolism Gene Expression Regulation, Developmental Heart Defects, Congenital/genetics,metabolism,pathology Heart Valve Diseases/genetics,metabolism,pathology Heart Valves/abnormalities,embryology,metabolism Humans Signal Transduction/genetics
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Combs Michelle D
Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center ML7020, 240 Albert Sabin Way, Cincinnati, OH 45229, USA.
Yutzey Katherine E
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Article Info
Journal
Circulation research
Abbr.
Circ Res
ISSN
1524-4571
DOI
10.1161/CIRCRESAHA.109.201566
Published
2009-08-28
Pages
408-21
Language
English
Region
United States
NLM ID
0047103
PMCID
PMC2777683
Subset
IM
Grants
NHLBI NIH HHS · R01 HL082716 · United States
NHLBI NIH HHS · P50 HL074728-050003 · United States
NHLBI NIH HHS · P50 HL074728 · United States
NHLBI NIH HHS · R01HL82716 · United States
NHLBI NIH HHS · R01 HL082716-03 · United States
External Links
PubMed source DOI: 10.1161/CIRCRESAHA.109.201566 PMC Full Text View journal details
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