Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer D J, Sessa W C, Walsh K
Division of Cardiovascular Research, St. Elizabeth's Medical Center of Boston, Massachusetts 02135, USA.
Nat Med. 2000 Sep;6(9):1004-10. doi: 10.1038/79510.
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.
近期研究表明，他汀类药物能够以一种独立于其降脂活性的方式发挥保护脉管系统的作用。我们在此表明，他汀类药物可在内皮细胞中快速激活蛋白激酶Akt/PKB。相应地，辛伐他汀以内皮型一氧化氮合酶（eNOS）依赖的方式增强了内源性Akt底物的磷酸化，抑制了细胞凋亡，并在体外加速了血管结构形成。与血管内皮生长因子（VEGF）治疗相似，辛伐他汀给药和内皮细胞中增强的Akt信号传导均促进了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，可解释他汀类药物的一些有益副作用，包括促进新血管生长。
