| Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. | |
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MedLine Citation:
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PMID: 21157040 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Congenital anomalies of the aortic valve are common and are associated with progressive valvular insufficiency and/or stenosis. In addition, aneurysm, coarctation, and dissection of the ascending aorta and aortic arch are often associated conditions that complicate patient management and increase morbidity and mortality. These associated aortopathies are commonly attributed to turbulent hemodynamic flow through the malformed valve leading to focal defects in the vessel wall. However, numerous surgical and pathological studies have identified widespread cystic medial necrosis and smooth muscle apoptosis throughout the aortic arch in affected patients. Here, we provide experimental evidence for an alternative model to explain the association of aortic vessel and valvular disease. Using mice with primary and secondary cardiac neural crest deficiencies, we have shown that neural crest contribution to the outflow endocardial cushions (the precursors of the semilunar valves) is required for late gestation valvular remodeling, mesenchymal apoptosis, and proper valve architecture. Neural crest was also shown to contribute to the smooth muscle layer of the wall of the ascending aorta and aortic arch. Hence, defects of cardiac neural crest can result in functionally abnormal semilunar valves and concomitant aortic arch artery abnormalities. |
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Authors:
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Rajan Jain; Kurt A Engleka; Stacey L Rentschler; Lauren J Manderfield; Li Li; Lijun Yuan; Jonathan A Epstein |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-12-13 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 121 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-05 Completed Date: 2011-02-03 Revised Date: 2012-02-07 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 422-30 Citation Subset: AIM; IM |
Affiliation:
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Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aortic Valve / abnormalities, embryology*, physiopathology Apoptosis Endocardial Cushion Defects / embryology, physiopathology Female Humans Mice Mice, Mutant Strains Models, Cardiovascular Neural Crest / abnormalities, embryology*, physiopathology Paired Box Transcription Factors / deficiency, genetics Pregnancy Receptors, Notch / genetics, physiology Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL095634/HL/NHLBI NIH HHS; U01 HL100405/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Paired Box Transcription Factors; 0/Receptors, Notch; 138016-91-8/Pax3 protein, mouse |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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