The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
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DOI：
10.1038/79510
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发表时间：
2000-09-01
期刊：
影响因子：
82.9
通讯作者：
Walsh, K
中科院分区：
文献类型：
--
作者：
Kureishi, Y;Luo, ZY;Walsh, K
最近的研究表明，他汀类药物可以以与其降脂活性无关的方式保护脉管系统。我们在此表明他汀类药物可快速激活内皮细胞中的蛋白激酶 Akt/PKB。因此，辛伐他汀以 Akt 依赖性方式增强内源性 Akt 底物内皮一氧化氮合酶 (eNOS) 的磷酸化，抑制细胞凋亡并加速体外血管结构形成。与血管内皮生长因子 (VEGF) 治疗类似，辛伐他汀给药和增强内皮细胞中的 Akt 信号传导均促进正常胆固醇血症兔缺血肢体的血管生成。因此，Akt 的激活代表了一种机制，可以解释他汀类药物的一些有益副作用，包括促进新血管生长。
Recent studies suggest that statins can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. We show here that statins rapidly activate the protein kinase Akt/PKB in endothelial cells. Accordingly, simvastatin enhanced phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibited apoptosis and accelerated vascular structure formation in vitro in an Akt-dependent manner. Similar to vascular endothelial growth factor (VEGF) treatment,both simvastatin administration and enhanced Akt signaling in the endothelium promoted angiogenesis in ischemic limbs of normocholesterolemic rabbits. Therefore, activation of Akt represents a mechanism that can account for some of the beneficial side effects of statins, including the promotion of new blood vessel growth.