Abstract
The peroxisome proliferator-activated receptors (PPARs) have been shown to be important in modulating vascular inflammation and atherosclerosis. Angiotensin II (Ang II) is known to promote vascular inflammation and accelerate atherosclerosis. We demonstrated that these vascular changes induced by Ang II are associated with up-regulation of pro-inflammatory genes, as well as down-regulation of PPAR-α expression. We hypothesized that a PPAR-α agonist would have vasculoprotective effects in a mouse model of Ang II-induced atherosclerosis by: 1) attenuation of pro-inflammatory mediators, 2) attenuation of arterial low-density lipoprotein (LDL) accumulation, and 3) attenuation of endothelial layer permeability. To examine the effects of a PPAR-α agonist on vascular inflammation, we administered a diet containing fenofibrate (40 mg/kg/day) for 5 weeks to male apolipoprotein E-deficient (apoE-KO) mice that were infused with Ang II (1.44 mg/kg/day). Fenofibrate reversed the pro-inflammatory genes induced by Ang II, and upregulated PPAR-α mRNA expression in the aorta. To determine whether fenofibrate could reverse the functional consequences of Ang II, arterial LDL accumulation and endothelial layer permeability from isolated mouse carotid arteries were assessed by quantitative fluorescence microscopy. Fenofibrate significantly attenuated both the rate of arterial LDL accumulation and endothelial layer permeability induced by acute administration of Ang II. Our studies demonstrate that PPAR-α activation has functional effects to reduce LDL accumulation and endothelial layer permeability in the arterial wall. The pleiotropic effects of PPAR-α agonists on vascular wall inflammation certainly participate in the inhibition of atherosclerosis development.
Original language | English (US) |
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Pages (from-to) | 1-16 |
Number of pages | 16 |
Journal | Journal of Applied Research |
Volume | 5 |
Issue number | 1 |
State | Published - 2005 |
Keywords
- Atherosclerosis
- Chemokines
- Endothelial cell
- Inflammation
- Lipoproteins
ASJC Scopus subject areas
- Medicine(all)
- Pharmacology