压应力对体外培养血管平滑肌细胞增殖影响及相关机制.pdf

Mechanism of static pressure mediated proliferation of vascular smooth muscle cell in vitro ABSTRACT Backgroud：When atherosclerosis and vessel intervention occurs, vascular endothelial cells are injured or vascular smooth muscle cells(VSMCs) migrate under endoderm, so that mechanical forces can directly affect VSMCs. Mechanical forces include stress, circular stress and static pressure. Mechanical stress induces VSMCs proliferation by activating extracellular signal-regulated kinase(ERK). However, the effect of static pressure on VSMCs proliferation is unclear. Objective: To investigate the effect of static pressure on VSMCs proliferation. Methods: VSMCs from rat aorta were respectively treated with different pressures of 0 mmHg, 120 mmHg, 180 mmHg, 240 mmHg in a self-manufactured pressure-adjustable cell incubator for 24hrs or were treated with 120 mmHg of static pressure for different time(0, 2, 4, 8, 12 and 24 hours). The proliferation of VSMCs was evaluated by means of cell counting and MTT assay, and the distribution of VSMCs’ cell cycles was detected by Flow Cytometry(FCM). and then the protein amount of Caveolin-1 and phosphor-ERK (p-ERK) was analyzed by Weston Blot. Results: VSMCs proliferation and ERK activation were significantly increased by static pressures in pressure-dependent manner, with the peak in 120 mmHg. When the static pressure was 120 mmHg, the peak was at 4 h. Interestingly, static pressure obviously inhibited caveolin-1 expression, which appeared a negative correlation with static pressure stimulated ERK activation. PD98059, an inhibitor of ERK kinase, and Cytochalasin D(Cyt D) that can destroy cell microfilament skeleton, both prohibited static pressure-induced VSMCs proliferation. Conclusion: Static pressure stimulates