Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

被引：10

作者：

Fei, Jia ^{[1
]}

Cook, Carla ^{[1
]}

Gillespie, Miriah ^{[1
]}

Yu, Bangning ^{[2
]}

Fullen, Khyra ^{[1
]}

Santanam, Nalini ^{[1
]}

机构：

[1] Marshall Univ, Dept Pharmacol Physiol & Toxicol, Joan C Edwards Sch Med, Huntington, WV 25755 USA

[2] LSU Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, New Orleans, LA USA

来源：

PPAR RESEARCH | 2011年 / 2011卷

关键词：

PROLIFERATOR-ACTIVATED-RECEPTOR; SMOOTH-MUSCLE-CELLS; EARLY GROWTH RESPONSE-1; NF-KAPPA-B; POLYUNSATURATED FATTY-ACIDS; GENE-EXPRESSION; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; OXIDIZED LIPIDS; GAMMA LIGANDS;

D O I：

10.1155/2011/753917

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Atherogenic omega-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs) and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate if omega-6 lipids modulated the early growth response-1 (Egr-1)/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs) were exposed to omega-6 lipids, linoleic acid (LA), or its oxidized form, 13-HPODE (OxLA) in the presence or absence of a PPAR alpha antagonist (MK886) or PPAR. antagonist (GW9662) or PPAR-specific siRNA. Our results demonstrate that omega-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels at the acute phase (1-4 hrs) when PPAR alpha was downregulated and at subacute phase (4-12 hrs) by modulating PPAR gamma, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action of omega-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.

引用

页数：11

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