Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Department of Physiology, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 2012 Dec;90(12):1559-68. doi: 10.1139/y2012-141. Epub 2012 Nov 29.
Mechanical stress contributes to hypertension and atherosclerosis partly through the stimulation of vascular smooth muscle cell (VSMC) proliferation. Oxidized low density lipoprotein (oxLDL) is another important atherogenic factor that can increase VSMC proliferation. The purpose of this study was to investigate whether oxLDL could further enhance the proliferative action of mechanical stretch on VSMC, and to determine the mechanism responsible for this interaction. Because nuclear protein import is critical in regulating gene expression, transcription, and cell proliferation, its involvement in the mitogenic effects of oxLDL and mechanical stress was studied. OxLDL enhanced the proliferative effects of mechanical stretch on its own in rabbit aortic VSMC, and induced increases in the expression of HSP60 in an additive manner. Adenoviral-mediated overexpression of HSP60 induced increases in cell proliferation compared with uninfected VSMC. Mechanical stretch and oxLDL stimulated the rate of nuclear protein import in VSMC and increased the expression of nucleoporins. These effects were sensitive to inhibition of the MAPK pathway. We conclude that oxLDL and mechanical stretch have a synergistic effect on VSMC proliferation. This synergistic effect is induced through a stimulation of nuclear protein import via HSP60 and an activation of the MAPK pathway.
机械应力通过刺激血管平滑肌细胞（VSMC）增殖在一定程度上导致高血压和动脉粥样硬化。氧化低密度脂蛋白（oxLDL）是另一种重要的动脉粥样硬化因子，可增加 VSMC 的增殖。本研究的目的是探讨 oxLDL 是否可以进一步增强机械拉伸对 VSMC 的增殖作用，并确定这种相互作用的机制。由于核蛋白输入对于调节基因表达、转录和细胞增殖至关重要，因此研究了其在 oxLDL 和机械应激的有丝分裂作用中的参与。oxLDL 本身增强了兔主动脉 VSMC 中机械拉伸的增殖作用，并以累加的方式诱导 HSP60 的表达增加。与未感染的 VSMC 相比，腺病毒介导的 HSP60 过表达诱导细胞增殖增加。机械拉伸和 oxLDL 刺激 VSMC 中的核蛋白输入率，并增加核孔蛋白的表达。这些作用对 MAPK 途径的抑制敏感。我们得出结论，oxLDL 和机械拉伸对 VSMC 的增殖具有协同作用。这种协同作用是通过 HSP60 刺激核蛋白输入和激活 MAPK 途径诱导的。
