Document Detail


Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves.
MedLine Citation:
PMID:  21157040     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rajan Jain; Kurt A Engleka; Stacey L Rentschler; Lauren J Manderfield; Li Li; Lijun Yuan; Jonathan A Epstein
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-12-13
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-02-03     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  422-30     Citation Subset:  AIM; IM    
Affiliation:
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
R01 HL095634/HL/NHLBI NIH HHS; U01 HL100405/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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


Previous Document:  Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL ...
Next Document:  Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis.