Peyton Kelly J, Liu Xiao-ming, Durante William
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, University of Missouri, One Hospital Drive, Columbia.
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA,
Front Biosci (Elite Ed). 2016 Jan 1;8(1):205-12. doi: 10.2741/E761.
The vascular endothelium is continuously exposed to cyclic mechanical strain due to the periodic change in vessel diameter as a result of pulsatile blood flow. Since emerging evidence indicates the cyclic strain plays an integral role in regulating endothelial cell function, the present study determined whether application of a physiologic regimen of cyclic strain (6% at 1 hertz) influences the proliferation of human arterial endothelial cells. Prolonged exposure of human dermal microvascular or human aortic endothelial cells to cyclic strain for up to 7 days resulted in a marked decrease in cell growth. The strain-mediated anti-proliferative effect was associated with the arrest of endothelial cells in the G2/M phase of the cell cycle, did not involve cell detachment or cytotoxicity, and was due to the induction of p21. Interestingly, the inhibition in endothelial cell growth was independent of the strain regimen since prolonged application of constant or intermittent 6% strain was also able to block endothelial cell proliferation. The ability of chronic physiologic cyclic strain to inhibit endothelial cell growth represents a previously unrecognized mechanism by which hemodynamic forces maintain these cells in a quiescent, non-proliferative state.
由于搏动性血流导致血管直径周期性变化，血管内皮持续受到周期性机械应变。鉴于新出现的证据表明周期性应变在调节内皮细胞功能中起不可或缺的作用，本研究确定施加生理周期应变方案（1赫兹下6%）是否会影响人动脉内皮细胞的增殖。将人真皮微血管内皮细胞或人主动脉内皮细胞长时间暴露于周期应变长达7天，导致细胞生长显著减少。应变介导的抗增殖作用与内皮细胞停滞于细胞周期的G2/M期有关，不涉及细胞脱离或细胞毒性，且是由p21的诱导所致。有趣的是，内皮细胞生长的抑制与应变方案无关，因为长时间施加恒定或间歇性6%的应变也能够阻断内皮细胞增殖。慢性生理性周期应变抑制内皮细胞生长的能力代表了一种此前未被认识的机制，通过该机制血流动力学力使这些细胞维持在静止、非增殖状态。
