2010•Arteriosclerosis Thrombosis and Vascular BiologyRequires access
CCN3 Inhibits Neointimal Hyperplasia Through Modulation of Smooth Muscle Cell Growth and Migration
TatsushiShimoyama, ShûichiHiraoka, MinoruTakemoto, MasayaKoshizaka, HirotakeTokuyama, TakahikoTokuyama, AkiWatanabe, MasakiFujimoto, HarukiyoKawamura, SeiyaSato, YuyaTsurutani, YasushiSaito, BernardPerbal, HaruhikoKoseki, KoutaroYokote
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Abstract
Objective— CCN3 belongs to the CCN family, which constitutes multifunctional secreted proteins that act as matrix cellular regulators. We investigated the pathophysiological roles of CCN3 in the vessels. Methods and Results— We examined the effects of CCN3 on the proliferation and migration of rat vascular smooth muscle cells (VSMC). CCN3 knockout mice were created, and vascular phenotypes and neointimal hyperplasia induced by photochemically induced thrombosis were investigated. CCN3 suppressed the VSMC proliferation induced by fetal bovine serum. The neutralizing antibody for transforming growth factor-β did not affect the growth inhibitory effect of CCN3. Moreover, CCN3 enhanced the mRNA expression of cyclin-dependent kinase inhibitors, p21 and p15. Gamma secretase inhibitor, an inhibitor of Notch signaling, partially inhibited the enhanced expression of p21 induced by CCN3. CCN3 also inhibited the VSMC migration. Finally, the histopathologic evaluation of the arteries 21 days after the endothelial inj...