Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis

Masatoyo Yoshioka, Shinsuke Yuasa, Keisuke Matsumura, Kensuke Kimura, Takayuki Shiomi, Naritaka Kimura, Chisa Shukunami, Yasunori Okada, Makio Mukai, Hankei Shin, Ryohei Yozu, Masataka Sata, Satoshi Ogawa, Yuji Hiraki, Keiichi Fukuda

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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.

Original languageEnglish
Pages (from-to)1151-1159
Number of pages9
JournalNature medicine
Volume12
Issue number10
DOIs
Publication statusPublished - 2006 Oct 1

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yoshioka, M., Yuasa, S., Matsumura, K., Kimura, K., Shiomi, T., Kimura, N., Shukunami, C., Okada, Y., Mukai, M., Shin, H., Yozu, R., Sata, M., Ogawa, S., Hiraki, Y., & Fukuda, K. (2006). Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis. Nature medicine, 12(10), 1151-1159. https://doi.org/10.1038/nm1476