Regulation of Endothelial Nitric Oxide Synthase and Endothelin-1 Expression by Fluvastatin in Human Vascular Endothelial Cells

[摘要] References(36)Cited-By(10)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 μM 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 μM 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.

[学科分类] 药理学

[关键词] Fluvastatin;3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor;Nitric oxide;Endothelin-1;Endothelial cell