Open AccessRegulation of Endothelial Nitric Oxide Synthase and Endothelin-1 Expression by Fluvastatin in Human Vascular Endothelial Cells
Author(s) -
Kazuyuki Ozaki,
Tadashi Yamamoto,
Takaharu Ishibashi,
Taku Matsubara,
Matomo Nishio,
Yoshifusa Aizawa
Publication year - 2001
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.85.147
Subject(s) - fluvastatin , enos , umbilical vein , nitric oxide , prostacyclin , endothelin 1 , endocrinology , medicine , nitric oxide synthase , incubation , chemistry , hmg coa reductase , endothelium , geranylgeraniol , reductase , biology , biochemistry , enzyme , in vitro , receptor , simvastatin
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.