Simvastatin attenuates TNF-α-induced apoptosis in endothelial progenitor cells via the upregulation of SIRT1
Simvastatin attenuates TNF-α-induced apoptosis in endothelial progenitor cells via the upregulation of SIRT1
复制标题
DOI：
10.3892/ijmm.2014.1740
复制
发表时间：
2014-07-01
影响因子：
5.4
通讯作者：
Li, Zicheng
中科院分区：
文献类型：
--
作者：
Du, Gang;Song, Yunlin;Li, Zicheng
内皮祖细胞（Endothelial progenitor cells，EPCs）来源于骨髓，可分为早期和晚期两种。本研究的重点是晚期EPCs，因为它们在血管生成和血管增殖中起重要作用。有证据表明，炎症和氧化变化可以增加EPC凋亡。值得注意的是，肿瘤坏死因子-α（TNF-α）是动脉粥样硬化发展的一个促成风险因素，并作为内皮细胞中的炎症介质和凋亡诱导剂发挥关键作用。此外，沉默调节蛋白家族的一员，沉默信息调节因子1型（SIRT 1），通过抑制p53和非p53依赖性细胞凋亡来促进细胞存活，以响应DNA损伤和氧化应激。他汀类药物也被证明通过其降脂和抗炎作用在预防内皮细胞凋亡和衰老中发挥关键作用。然而，很少有证据表明他汀类药物本身减弱TNF-α诱导的EPC凋亡。本研究的目的是证明最常用的他汀类药物之一辛伐他汀在减少TNF-α诱导的EPCs凋亡方面的有效性。结果表明，SIRT 1蛋白表达下降，TNF-α在时间和剂量依赖性的方式，而TNF-α引起的凋亡EPCs的百分比显着增加，辛伐他汀的应用降低了这个百分比。高浓度辛伐他汀可促进SIRT 1的表达，促进EPCs增殖。总之，这项研究的结果表明，辛伐他汀是至关重要的，在抵消TNF-α诱导的内皮祖细胞凋亡，这种保护可能涉及SIRT 1的行动。
Endothelial progenitor cells (EPCs) originate from the bone marrow and can be classified as either early or late EPCs. The focus of this study was on late EPCs, as they play an important role in angiogenesis and vascular proliferation. Evidence suggests that inflammatory and oxidative changes can increase EPC apoptosis. Of note, tumor necrosis factor-alpha (TNF-alpha) is a contributing risk factor to the development of atherosclerosis and plays a key role as both an inflammatory mediator and an inducer of apoptosis in endothelial cells. Additionally, a member of the sirtuin family, silent information regulator type-1 (SIRT1), promotes cell survival by repressing p53- and non-p53-dependent apoptosis in response to DNA damage and oxidative stress. Statins have also been shown to play a key role in the prevention of endothelial apoptosis and senescence via their lipid-lowering and anti-inflammatory actions. However, there is little evidence that statins themselves attenuate EPC apoptosis induced by TNF-alpha. The aim of this study was to demonstrate the effectiveness of one of the most commonly used statins, simvastatin, on decreasing TNF-alpha-induced apoptosis in EPCs. The results indicated that SIRT1 protein expression was decreased by TNF-alpha in a time- and dose-dependent manner and that while TNF-alpha caused a marked increase in the percentage of apoptotic EPCs, application of simvastatin decreased this percentage. A high concentration of simvastatin promoted the expression of SIRT1 and increased the proliferation of EPCs. In conclusion, findings of this study showed that simvastatin is crucial in counteracting the TNF-alpha-induced apoptosis of EPCs and that this protection may involve the actions of SIRT1.