Simvastatin and Ca(2+) signaling in endothelial cells: involvement of rho protein.
Simvastatin and Ca(2+) signaling in endothelial cells: involvement of rho protein.
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内皮细胞中的辛伐他汀和 Ca(2 ) 信号传导：rho 蛋白的参与。
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
R. Andriantsitohaina
中科院分区：
文献类型：
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作者：
M. Alvarez de Sotomayor;R. Andriantsitohaina
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂辛伐他汀除了具有降脂作用外，还能产生内皮依赖性舒张作用。在牛主动脉内皮细胞（BAEC）中研究了潜在的机制。辛伐他汀通过从对毒胡萝卜素和ryanodine敏感的细胞内钙库中释放Ca（2+），并增加Ca（2+）内流，诱导BAEC胞浆Ca（[Ca（2+）]（i）增加。磷脂酶A2抑制剂ONO-RS-082或超氧化物歧化酶和过氧化氢酶联合使用均未改变辛伐他汀的反应。然而，对辛伐他汀的反应被HMG-CoA还原酶的产物甲羟戊酸或Rho家族的小G蛋白的抑制剂肉毒梭菌C3毒素降低。因此，[Ca（2+）]（i）的增加涉及通过甲羟戊酸依赖性途径激活Rho蛋白对于辛伐他汀的作用是必不可少的，并且可能有助于其对血管疾病的有益作用。本研究有助于阐明辛伐他汀在BAEC中产生内皮因子的机制。
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin is able to produce endothelium-dependent relaxation in addition to its lipid-lowering properties. The underlying mechanisms were investigated in bovine aortic endothelial cells (BAEC). Simvastatin induced an increase in cytosolic calcium ([Ca(2+)](i)) in BAEC, by releasing Ca(2+) from intracellular stores sensitive to thapsigargin and ryanodine, and increasing Ca(2+) entry. Simvastatin response was not altered by the phospholipase A(2) inhibitor ONO-RS-082, or the combination of superoxide dismutase plus catalase. However, the response to simvastatin was reduced by the product of HMG-CoA reductase, mevalonate or by the inhibitor of small G proteins of the Rho family, Clostridium botulinum C3 toxin. Thus, increase in [Ca(2+)](i) involving the activation of Rho protein through mevalonate-dependent pathway is essential for the action of simvastatin and might contribute to its beneficial effects against vascular diseases. This study helps elucidate the mechanisms of endothelial factor generation by simvastatin in BAEC.
影响因子：
158.5
作者：
TREASURE, CB;KLEIN, JL;ALEXANDER, RW
通讯作者：
ALEXANDER, RW
影响因子：
37.8
作者：
Laufs, U;La Fata, V;Liao, JK
通讯作者：
Liao, JK
影响因子：
37.8
作者：
Hu, QH;Corda, S;Ziegelstein, RC
通讯作者：
Ziegelstein, RC