Chondromodulin-I maintains normal cardiac valves by preventing angiogensis

We recently identified chondromodulin-I as a crucial antiangiogenic factor for maintaining cardiac valvular function. Normally, avascular cardiac valves from ApoE^-/- mice and humans with valvular heart disease showed angiogenesis and increased expression of vascular endothelial cell growth factor and matrix metalloproteinases, with downregulation of chondromodulin-I. Conditioned medium from cultured valvular interstitial cells inhibited tube formation and migration of endothelial cells, and this effect was rescued by chondromodulin-I siRNA. Cardiac valves of chondromodulin-I-knockout mice showed neovascularization, lipid deposition and calcification, indicating early aortic stenosis. These findings implicated chondromodulin-I as a critical factor for maintaining normal cardiac valves by preventing angiogenesis.