• 作者：David Á ; lvarez-Guardia^a ; Xavier Palomer^a ; Mercy M. Davidson^b ; Ilhem El Kochairi^c ; Liliane Michalik^c ; Walter Wahli^c ; Manuel Vá ; zquez-Carrera^a ; ^{mvazquezcarrera@ub.edu}
• 关键词：Coraz&oacute ; n ; GW501516 ; PPAR尾/未 ; Inflamaci&oacute ; n ; NF-魏B
• 刊名：Cl篓陋nica e Investigaci篓庐n en Arteriosclerosis
• 出版年：2012
• 期刊代码：pca88_02149168
• 类别：med
• 出版时间：May-June, 2012
• 卷：24
• 期：3
• 页码：131-140
• 文件大小：1047 K

Introduction

High-fat diet intake is associated with cardiac disorders characterised by a low-grade inflammatory process which involves NF-魏B activation. PPAR尾/未 has been proposed as a potential therapeutic target to mitigate the inflammatory process related to cardiovascular disorders. However, the involvement of this receptor in lipid-induced inflammatory response in the heart is not yet known.

Methods

The inflammatory profile was determined in hearts using mice fed with a high-fat diet (HFD) in the presence or absence of the PPAR尾/未 agonist GW501516, in hearts from knockout PPAR尾/未 mice, and in palmitate-exposed human cardiac AC16 cells in the presence or absence of GW501516 and the PPAR尾/未 antagonist GSK0660.

Results

GW501516 treatment reduced the induction in the cardiac expression of IL-6, MCP-1 and TNF-伪, as well as the increase in DNA-binding NF-魏B activity, in mice fed the HFD. Furthermore, hearts from knockout PPAR尾/未 mice exhibited increased IL-6 and MCP-1 levels, as well as higher NF-魏B DNA-binding activity. In AC16 cells, GW501516 treatment reduced the expression of TNF-伪 and MCP-1, as well as the increase in NF-魏B DNA-binding activity caused by palmitate. GW501516 addition to these cells increased the interaction between PPAR尾/未 and the p65 subunit of NF-魏B, whereas it was prevented in the presence of the PPAR尾/未 antagonist GSK0660.

Conclusions

PPAR尾/未 activation reduces lipid-induced inflammation in cardiac cells through a mechanism involving the physical interaction between PPAR尾/未 and p65.