氟伐他汀对人血管内皮细胞中内皮型一氧化氮合酶和内皮素-1表达的调节作用

Regulation of endothelial nitric oxide synthase and endothelin-1 expression by fluvastatin in human vascular endothelial cells.

作者信息

Ozaki K, Yamamoto T, Ishibashi T, Matsubara T, Nishio M, Aizawa Y

机构信息

First Department of Internal Medicine, Institute of Nephrology, Niigata University School of Medicine, Japan.

出版信息

Jpn J Pharmacol. 2001 Feb;85(2):147-54. doi: 10.1254/jjp.85.147.

DOI:10.1254/jjp.85.147

PMID:11286396

Abstract

We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on endothelial vasoactive substances using human umbilical vein endothelial cells (HUVECs). Incubation of HUVECs with fluvastatin for 12 h increased endothelial nitric oxide synthase (eNOS) mRNA expression in a concentration-dependent manner (peak, 276 +/- 38%, mean +/- S.D., of the control, at 1.0 microM fluvastatin, P<0.01). In addition, fluvastatin increased eNOS protein production (245 +/- 51% of the control level, P<0.05) as well as nitrite production (165 +/- 35% of the control level, P<0.01). In contrast, incubation of HUVECs with 1.0 microM fluvastatin for 12 h significantly reduced the production of endothelin-1 (ET-1) and preproET-1 mRNA expression in HUVECs (28 +/- 1% and 39 +/- 1% of the control level, respectively, P<0.01). Our results suggest that fluvastatin might be involved in improvement of endothelial function and prevention of the progression of atherosclerosis.

摘要

我们使用人脐静脉内皮细胞（HUVECs）研究了3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂氟伐他汀对内皮血管活性物质的影响。用氟伐他汀孵育人脐静脉内皮细胞12小时，可使内皮型一氧化氮合酶（eNOS）mRNA表达呈浓度依赖性增加（在1.0微摩尔/升氟伐他汀时达到峰值，为对照的276±38%，平均值±标准差，P<0.01）。此外，氟伐他汀增加了eNOS蛋白生成（为对照水平的245±51%，P<0.05）以及亚硝酸盐生成（为对照水平的165±35%，P<0.01）。相反，用1.0微摩尔/升氟伐他汀孵育人脐静脉内皮细胞12小时，可显著降低人脐静脉内皮细胞中内皮素-1（ET-1）的生成和前内皮素-1 mRNA表达（分别为对照水平的28±1%和39±1%，P<0.01）。我们的结果表明，氟伐他汀可能参与改善内皮功能和预防动脉粥样硬化进展。