Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.
Nat Med
; 12(10): 1151-9, 2006 Oct.
Article
in En
| MEDLINE
| ID: mdl-16980969
ABSTRACT
The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.
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Database:
MEDLINE
Main subject:
Aorta
/
Intercellular Signaling Peptides and Proteins
/
Heart Valve Diseases
/
Membrane Proteins
/
Mitral Valve
/
Neovascularization, Pathologic
Limits:
Aged
/
Animals
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Nat Med
Journal subject:
BIOLOGIA MOLECULAR
/
MEDICINA
Year:
2006
Type:
Article
Affiliation country:
Japan