Kazuyuki Ozaki1,*, Tadashi Yamamoto2, Takaharu
Ishibashi3, Taku Matsubara1, Matomo Nishio3
and Yoshifusa Aizawa1
1First Department of Internal Medicine, 2Department
of Renal Pathology, Institute of Nephrology, Niigata University School of
Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan
3Department of Pharmacology, Kanazawa Medical University, 1-1
Daigaku, Uchinada, Ishikawa 920-0293, Japan
*Corresponding author. FAX: +81-25-227-0774
E-mail: k-ozaki@med.niigata-u.ac.jp
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 mM 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 mM 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.
Keywords: Fluvastatin, 3-Hydroxy-3-methylglutaryl coenzyme A reductase
inhibitor, Nitric oxide, Endothelin-1, Endothelial cell
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