Role of anti-angiogenic factor chondromodulin-I for maintaining cardiac valvular function

Daihiko Hakuno, Keiichi Fukuda

研究成果: Review article

4 引用 (Scopus)

抜粋

Cardiac valves are recognized as avascular tissue as well as cartilage and eye. We recently identified chondromodulin-I as crucial anti-angiogenic factor for maintaining cardiac valvular function. chondromodulin-I was first detected at developmental stage E9.5 in outflow tract, valvular primordium, and left ventricle, but was restricted to cardiac valves from late embryogenesis to adult. In ApoE(-/-) mice and human valvular heart diseases such as atherosclerosis, rheumatic heart diseases, and infective endocarditis, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) expression and neovascularization were observed in the area of down-regulation of chondromodulin-I. Conditioned medium from cultured-valvular interstitial cells strongly inhibited tube formation and migration of endothelial cells, and these effects were partially blocked by chondromodulin-I siRNA in vitro. Gene targeting of chondromodulin-I caused VEGF expression, neovascularization, lipid deposition, and calcification in cardiac valves of aged mice. Echocardiography showed aortic valve thickening and turbulent flow suggesting early stage of aortic stenosis. These findings provide evidence that chondromodulin-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis that may lead to valvular heart diseases.

元の言語English
ページ(範囲)361-372
ページ数12
ジャーナルClinical calcium
17
発行部数3
出版物ステータスPublished - 2007 3

ASJC Scopus subject areas

  • Medicine(all)

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