| pubmed-article:20731356 | pubmed:abstractText | Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis. ?-Sitosterol, an important phytosterol found in plant food, is known to exert antiatherosclerosis activity. However, the molecular mechanisms underlying ?-sitosterol-induced antiproliferation of VSMCs were still not clear. This study demonstrated that ?-sitosterol (1-20 ?M) concentration-dependently inhibited proliferation of rat aortic smooth muscle cells (RASMCs) without cytotoxic effect. Flow cytometric analysis revealed that ?-sitosterol arrested cell cycle progression through down-regulation of cyclin E and cyclin-dependent kinase (CDK)2 and up-regulation of p21cip1. In the ?-sitosterol-treated RASMCs, the formation of the CDK2-p21cip1 complex was increased and the assayable CDK2 activity was decreased. Knockdown of the expression of p21cip1 gene prevented ?-sitosterol-induced cell cycle arrest in RASMCs. In conclusion, ?-sitosterol inhibited VSMC proliferation by increasing the levels of p21cip1 protein, which in turn inhibited the CDK2 activity, and finally interrupted the progress of the cell cycle. | lld:pubmed |
