Direct antiatherosclerotic effects of PPAR agonists

Abstract

It is anticipated that the antiatherosclerotic effects of PPAR agonists observed in experimental studies will translate into reduced cardiovascular events. This promise is yet to be realized in short-to-medium term studies. Given the central role of the PPAR in gene regulation, particularly in metabolic states, it is possible that more targeted modulation of PPAR signalling may hold many rewards for the prevention of atherosclerosis.

Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

“…In addition, the HDL-raising effects of fibrates were ascribed to a reduction in CETP (Chapman et al, 2010;van der Hoogt et al, 2007). Fibrates also inflict direct anti-oxidant and anti-inflammatory effects (Jandeleit-Dahm et al, 2009;Kooistra et al, 2006).…”

“…remnants clearance, β-oxidation (Bijland et al, 2010), apolipoprotein A-I/II expression and cholesterol efflux from macrophages (Jandeleit-Dahm et al, 2009;Lalloyer and Staels, 2010). In addition, the HDL-raising effects of fibrates were ascribed to a reduction in CETP (Chapman et al, 2010;van der Hoogt et al, 2007).…”

“…The effects of PPAR isoforms (α, γ) on glucose and lipid metabolism have led to the development of PPAR agonists for the treatment of hyperglycemia and dyslipidemia (Jandeleit-Dahm et al, 2009;Lalloyer and Staels, 2010).…”

The PPAR-RXR Transcriptional Complex in the Vasculature

“…22,23 PPAR␥ also regulates redox balance and inflammation, including specific chemokines and chemokine receptors (Figure 2). 24,25 Interestingly, EPCs, redox balance, and PPAR␥ activation may be interconnected. 26 GPIHBP1 (glycosylphosphatidylinositolanchored high-density lipoprotein-binding protein 1), a novel endothelial cofactor for lipoprotein lipase (LPL), is PPAR␥-regulated and may help link insulin resistance to hypertriglyceridemia.…”

PPARδ modulates oxLDL-induced apoptosis of vascular smooth muscle cells through a TGF-β/FAK signaling axis

“…Peroxisome proliferator-activated receptor delta (PPAR␦) is a ligand-activated transcription factor implicated in diverse pathophysiological processes including vascular disorders (Ehrenborg and Krook, 2009;Jandeleit-Dahm et al, 2009). Activation of PPAR␦ suppresses the proliferation and inflammation of vascular smooth muscle cells (VSMCs) through upregulation of transforming growth factor-␤1 (TGF-␤1) .…”