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首页> 外文期刊>Endothelium: Journal of endothelial cell research >Atorvastatin neutralizes the up-regulation of thrombospondin-1 induced by thrombin in human umbilical vein endothelial cells.
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Atorvastatin neutralizes the up-regulation of thrombospondin-1 induced by thrombin in human umbilical vein endothelial cells.

机译：阿托伐他汀可中和人脐静脉内皮细胞中凝血酶诱导的血小板反应蛋白-1的上调。

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摘要

Statins have been reported to affect blood vessel formation. Thrombospondin-1 (TSP-1) is a multifunctional protein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. This study was designed to investigate the effect of atorvastatin on TSP-1 synthesis in thrombin-stimulated human umbilical vein endothelial cells (HUVECs), and its regulation by mevalonate or its derivatives. The results showed that atorvastatin down-regulated TSP-1 expression in HUVECs. This effect was fully reversed by mevalonate, farnesylpyrophosphate (FPP), and gerarylgeranylpyrophosphate (GGPP). Furthermore, farnesyltransferase and geranylgeranyltransferase inhibitors decreased TSP-1expression. It was also found that thrombin increased TSP-1 expression in HUVECs. Atorvastatin (0.1, 1, and 10 muM) decreased TSP-1 in thrombin-stimulated cells (45%, 66%, and 80%). Mevalonate partially reversed this inhibitory effect of atorvastatin on TSP-1, whereas the presence of FPP and GGPP did not alter TSP-1. Rho-kinase inhibitor neutralized the up-regulation of TSP-1 induced by thrombin. In conclusion, atorvastatin inhibits TSP-1 expression in endothelial cells via the mevalonate pathway. Rho protein activation is necessary for up-regulation of TSP-1 synthesis induced by thrombin. Because FPP and GGPP are essential for the activity of Rho proteins, inhibition of these proteins may constitute the mechanism by which atorvastatin inhibits thrombin up-regulated TSP-1 expression.
机译：据报道他汀类药物会影响血管的形成。血小板反应蛋白-1（TSP-1）是一种多功能蛋白，可影响脉管系统，例如血小板活化，血管生成和伤口愈合。本研究旨在研究阿托伐他汀对凝血酶刺激的人脐静脉内皮细胞（HUVEC）中TSP-1合成的影响，以及甲羟戊酸或其衍生物对其的调节作用。结果表明，阿托伐他汀下调HUVECs中TSP-1的表达。甲羟戊酸酯，法呢基焦磷酸酯（FPP）和香叶基香叶基香烷基焦磷酸酯（GGPP）完全逆转了这种作用。此外，法呢基转移酶和香叶基香叶基转移酶抑制剂可降低TSP-1的表达。还发现凝血酶增加了HUVEC中TSP-1的表达。阿托伐他汀（0.1、1和10μM）降低了凝血酶刺激细胞（45％，66％和80％）中的TSP-1。甲羟戊酸酯部分逆转了阿托伐他汀对TSP-1的抑制作用，而FPP和GGPP的存在并未改变TSP-1。 Rho激酶抑制剂中和了凝血酶诱导的TSP-1的上调。总之，阿托伐他汀通过甲羟戊酸途径抑制内皮细胞中TSP-1的表达。 Rho蛋白激活对于凝血酶诱导的TSP-1合成的上调是必需的。由于FPP和GGPP对于Rho蛋白的活性至关重要，因此抑制这些蛋白可能构成阿托伐他汀抑制凝血酶上调TSP-1表达的机制。

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