HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ohkita, M. Articles by Matsumura, Y. Search for Related Content PubMed PubMed Citation Articles by Ohkita, M. Articles by Matsumura, Y.

---

VASCULAR AND HYPERTENSION

Differential Effects of Different Statins on Endothelin-1 Gene Expression and Endothelial NOS Phosphorylation in Porcine Aortic Endothelial Cells

Mamoru Ohkita^*, Masato Sugii^*, Yuki Ka^*, Ayako Kitamura^*, Tatsuhiko Mori, Tetsuya Hayashi, Masanori Takaoka^* and Yasuo Matsumura^*,1

^* Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan; and Third Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan

To whom requests for reprints should be addressed at ¹ Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4–20–1 Nasahara, Takatsuki, Osaka 569-1094, Japan. E-mail: matumrh{at}gly.oups.ac.jp

Abstract

It has been reported that 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors (statins) produce a variety of cardiovascular protective effects independent of their ability to lower total and low-density lipoprotein cholesterol. Recent studies have also reported that statins produce pleiotropic effects through improved endothelial function, enhanced fibrinolysis, and antithrombotic actions. In the present study, we examined the effects of pitavastatin, pravastatin, atorvastatin, and cerivastatin on endothelin (ET)-1 production in cultured porcine aortic endothelial cells (PAECs). Treatment with cerivastatin but not pitavastatin, pravastatin, or atorvastatin decreased basal and TNF-–stimulated ET-1 release from PAECs in a dose-dependent manner (1–10 µM). Northern blot analysis showed that cerivastatin markedly suppressed prepro ET-1 mRNA expression in both conditions. In addition, these inhibitory effects of cerivastatin on ET-1 release and prepro ET-1 mRNA expression were completely abolished by simultaneous treatment with 200 µM mevalonate. Furthermore, cerivastatin did not have any effects on endothelial nitric oxide synthase (eNOS) protein levels, but induced eNOS phosphorylation at Ser1177. From these findings, it is most likely that cerivastatin suppresses ET-1 production, possibly through an increase in eNOS activity and the subsequent nitric oxide production in PAECs. These findings also suggest that cerivastatin may have beneficial effects on ET-1–related diseases.

Key Words: statin • endothelin-1 • endothelial cells • endothelial nitric oxide synthase