Peroxisome proliferator-activated receptor α agonists increase nitric oxide synthase expression in vascular endothelial cells

被引：143

作者：

Goya, K ^{[1
]}

Sumitani, S ^{[1
]}

Xu, X ^{[1
]}

Kitamura, T ^{[1
]}

Yamamoto, H ^{[1
]}

Kurebayashi, S ^{[1
]}

Saito, H ^{[1
]}

Kouhara, H ^{[1
]}

Kasayama, S ^{[1
]}

Kawase, I ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Mol Med, Osaka, Japan

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2004年 / 24卷 / 04期

关键词：

atherosclerosis; endothelium; nitric oxide; vascular biology; vasodilatation;

D O I：

10.1161/01.ATV.0000118682.58708.78

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective-There has been accumulating evidence demonstrating that activators for peroxisome proliferator-activated receptor alpha (PPARalpha) have antiinflammatory, antiatherogenic, and vasodilatory effects. We hypothesized that PPARalpha activators can modulate endothelial nitric oxide synthase (eNOS) expression and its activity in cultured vascular endothelial cells. Methods and Results-Bovine aortic endothelial cells were treated with the PPARalpha activator fenofibrate. The amount of eNOS activity and the expression of eNOS protein and its mRNA were determined. Our data show that treatment with fenofibrate for 48 hours resulted in an increase in eNOS activity. Fenofibrate failed to increase eNOS activity within 1 hour. Fenofibrate also increased eNOS protein as well as its mRNA levels. RU486, which has been shown to antagonize PPARalpha action, inhibited the fenofibrate-induced upregulation of eNOS protein expression. WY14643 and bezafibrate also increased eNOS protein levels, whereas rosiglitazone did not. Transient transfection experiments using human eNOS promoter construct showed that fenofibrate failed to enhance eNOS promoter activity. Actinomycin D studies demonstrated that the half-life of eNOS mRNA increased with fenofibrate treatment. Conclusions-PPARalpha activators upregulate eNOS expression, mainly through mechanisms of stabilizing eNOS mRNA. This is a new observation to explain one of the mechanisms of PPARalpha-mediated cardiovascular protection.

引用

页码：658 / 663

页数：6

共 46 条

[41] Peroxisome proliferator-activated receptor γ ligands are potent inhibitors of angiogenesis in vitro and in vivo [J].