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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Oxidized LDL enhances stretch-induced smooth muscle cell proliferation through alterations in nuclear protein import
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Oxidized LDL enhances stretch-induced smooth muscle cell proliferation through alterations in nuclear protein import

机译：氧化的低密度脂蛋白通过改变核蛋白的进口来增强拉伸诱导的平滑肌细胞增殖

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摘要

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.
机译：机械应力部分通过刺激血管平滑肌细胞（VSMC）增殖而导致高血压和动脉粥样硬化。氧化的低密度脂蛋白（oxLDL）是另一个重要的动脉粥样硬化因子，可以增加VSMC增殖。这项研究的目的是调查oxLDL是否可以进一步增强机械拉伸对VSMC的增殖作用，并确定引起这种相互作用的机制。由于核蛋白的导入对于调节基因表达，转录和细胞增殖至关重要，因此研究了其参与oxLDL的促有丝分裂作用和机械应力。 OxLDL自身增强了机械拉伸在兔主动脉VSMC中的增殖作用，并以累加方式诱导了HSP60表达的增加。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刺激了VSMC中核蛋白的导入速率并增加了核孔蛋白的表达。这些作用对抑制MAPK途径敏感。我们得出结论，oxLDL和机械拉伸对VSMC增殖具有协同作用。这种协同作用是通过刺激HSP60导入核蛋白并激活MAPK途径来诱导的。

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