Induction of Haemeoxygenase-1 Improves FFA-Induced Endothelial Dysfunction in Rat Aorta

被引：24

作者：

Han, Fang ^{[1
]}

Hui, Zongguang ^{[2
]}

Zhang, Shuxian ^{[3
]}

Hou, Ningning ^{[2
]}

Wang, Yali ^{[2
]}

Sun, Xiaodong ^{[2
]}

机构：

[1] Weifang Med Univ, Affiliated Hosp, Dept Pathol, Weifang 261031, Shandong, Peoples R China

[2] Weifang Med Univ, Affiliated Hosp, Dept Endocrinol, Weifang 261031, Shandong, Peoples R China

[3] Weifang Med Univ, Affiliated Hosp, Med Imaging Ctr, Dept Magnet Resonance Imaging, Weifang 261031, Shandong, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2015年 / 35卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Haemeoxygenase-1; Free fatty acids; Endothelial dysfunction; ISCHEMIA-REPERFUSION; HEME OXYGENASE; CARDIOVASCULAR-DISEASE; NITRIC-OXIDE; ADIPONECTIN; INCREASES; GLUCOSE; MICROALBUMINURIA; OVEREXPRESSION; EXPRESSION;

D O I：

10.1159/000373946

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Background: The induction of haemeoxygenase-1 (HO-1) exerts beneficial effects in the setting of endothelial dysfunction in obesity. High free fatty acid (FFA) levels are a common feature of obesity and are the primary cause of endothelial dysfunction. The objective of our study was to explore the effects of HO-1 induction on FFA-induced endothelial dysfunction in rats. Methods: Rats received FFA treatment with either cobalt protoporphyrin (CoPP) to induce HO-1 or stannous protoporphyrin (SnPP) to inhibit HO-1. Endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) production, superoxide production and nuclear factor (NF)-kappa B expression in the aorta were each determined. The levels of adenosine monophosphate (AMP)-activated kinase (AMPK) and endothelial nitric oxide synthase (eNOS) expression in endothelial cells were determined via Western blotting. Results: Induction of HO-1 by CoPP decreased circulating FFA, high-sensitivity C-reactive protein and malondialdehyde levels and increased serum adiponectin and glutathione levels compared with the FFA group (P<0.05). High FFA levels resulted in EDV impairment, which was improved by HO-1 induction (P<0.05). Induction of HO-1 increased NO levels and reduced aortic superoxide production and NF-kappa B expression compared with the FFA group. The FFA group exhibited decreased AMPK expression and eNOS phosphorylation, both of which were enhanced via HO-1 induction (P<0.05). The beneficial effects of CoPP on EDV were partially attenuated in vitro in the presence of inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K), and eNOS. Conclusions: HO-1 induction with CoPP improves FFA-induced endothelial dysfunction in the rat aorta. The protective mechanism appears to be related to the activation of the AMPK-PI3K-eNOS pathway as a result of increased adiponectin levels as well as decreased inflammation and oxidative stress. Copyright (C) 2015 S. Karger AG, Basel

引用

页码：1230 / 1240

页数：11

共 37 条

[1]

Pharmacological and clinical aspects of heme oxygenase [J].