Thrombosis and Atherosclerosis Research Institute, 237 Barton St East, Hamilton, Ontario, L8L 2X2 Canada.
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2609-15. doi: 10.1161/ATVBAHA.112.300090. Epub 2012 Sep 20.
Statins decrease mortality in patients with vascular disorders, and evidence for the pleiotropic effects of statins is accumulating. Statins enhance endothelial NO synthase (eNOS) expression, thereby attenuating platelet activation and thrombus formation. Our goal was to determine whether statins have eNOS-independent effects on platelet activation.
Wild-type and eNOS-deficient mice were given a 14-day course of oral atorvastatin, and platelet activation was evaluated in vitro and in vivo. Whereas in wild-type mice atorvastatin inhibited platelet activation in vitro in response to numerous agonists, in eNOS-deficient mice, atorvastatin inhibited only thrombin-induced and protease-activated receptor 4 agonist peptide-induced platelet activation. Consistent with an eNOS-independent effect, atorvastatin inhibited platelet activation in vivo in both wild-type and eNOS-deficient mice.
Atorvastatin inhibits platelet activation via eNOS-dependent and eNOS-independent mechanisms with the latter restricted to protease-activated receptor 4-induced activation downstream to the receptor.
他汀类药物可降低血管疾病患者的死亡率，且他汀类药物多效性作用的证据正在不断增加。他汀类药物可增强内皮型一氧化氮合酶（eNOS）的表达，从而减轻血小板激活和血栓形成。我们的目的是确定他汀类药物是否对血小板激活具有 eNOS 非依赖性作用。
给予野生型和 eNOS 缺陷型小鼠 14 天的口服阿托伐他汀治疗，并在体外和体内评估血小板激活。尽管阿托伐他汀可抑制野生型小鼠对多种激动剂的体外血小板激活，但在 eNOS 缺陷型小鼠中，阿托伐他汀仅抑制凝血酶诱导和蛋白酶激活受体 4 激动肽诱导的血小板激活。与 eNOS 非依赖性作用一致，阿托伐他汀可抑制野生型和 eNOS 缺陷型小鼠体内的血小板激活。
阿托伐他汀通过 eNOS 依赖性和 eNOS 非依赖性机制抑制血小板激活，后者仅限于受体下游的蛋白酶激活受体 4 诱导的激活。
