Physiological cyclic stretch causes cell cycle arrest in cultured vascularsmooth muscle cells

Smooth muscle cells (SMC) are the major cellular component of the blood ves sel wall and are continuously exposed to cyclic stretch due to pulsatile bl ood flow This study examined the effects of a physiologically relevant leve l of cyclic stretch on rat aortic vascular SMC proliferation. Treatment of static SMC with serum, platelet-derived growth factor, or thrombin stimulat ed SMC proliferation, whereas exposure of SMC to cyclic stretch blocked the proliferative effect of these growth factors. The stretch-mediated inhibit ion in SMC growth was not due to cell detachment or increased cell death. F low cytometry analysis revealed that cyclic stretch increased the fraction of SMC in the G(0)/G(1) phase of the cell cycle. Stretch-inhibited G(1)/S p hase transition was associated with a decrease in retinoblastoma protein ph osphorylation and with a selective increase in the cyclin-dependent kinase inhibitor p21, but not p27. These results demonstrate that cyclic stretch i nhibits SMC growth by blocking cell cycle progression and suggest that phys iological levels of cyclic stretch contribute to vascular homeostasis by in hibiting the proliferative pathway of SMC.