Peroxisome Proliferator‐Activated Receptors in the Modulation of the Immune/Inflammatory Response in Atherosclerosis

Abstract

Inflammation has been recognized as an important hallmark of atherosclerosis. The pharmacological activation of PPAR-γ by the thiazolidinediones in diabetes, and of PPAR-α by the fibrates in hyperlipidemia has been shown to help to reduce inflammatory markers in preclinical and clinical studies. PPARs are known to modulate immune pathways through at least three different mechanisms: by direct binding to PPRE of anti-inflammatory cytokines genes; by transrepression of transcription factors like NF-κB and AP-1; or by corepression. The regulation of the inflammatory pathways by PPARs can be achieved on each one of the cells involved in the atherosclerotic process, that is, monocytes, macrophages, T cells, endothelial cells, and smooth muscle cells. Moreover, as each of these cellular components is interconnected with each other, PPAR activation in one cell type could affect the other ones. As activation of PPARs has clear ant-inflammatory benefits, PPARs ligands should be considered as a new therapeutical approach to ameliorate the exacerbated immune response in atherosclerotic diseases.

Rhizoma Dioscoreae Nipponicae polysaccharides protect HUVECs from H2O2-induced injury by regulating PPARγ factor and the NADPH oxidase/ROS–NF-κB signal pathway

“…PPAR and their agonists have been gaining more attention recently in regard to the study of the mechanisms involved in the etiology and pathogenesis of AS (Fernandez, 2008). The pharmacological modulations of PPARg can be linked to an improvement on the low-grade inflammation (Cuzzocrea et al, 2004;Adamiec et al, 2007).…”

Peroxisome proliferator-activated receptors, Metabolic Syndrome and Cardiovascular Disease

“…TZDs also selectively stimulate PPARγ gene promoter activity and modulate the expression of a number of PPARγ target genes [49]. Studies in both humans and animals indicate that TZDs, rosiglitazone and pioglitazone (PPARγ agonists) ameliorate hyperglycemia by reversing insulin resistance and improving insulin sensitivity [49,165–170]. Likewise, PPARγ agonists attenuate hyperlipidemia-induced elevation by circulating FFAs, lipotoxic accumulation of lipid in peripheral tissues and insulin resistance.…”

MicroRNA-21 targets peroxisome proliferators-activated receptor-α in an autoregulatory loop to modulate flow-induced endothelial inflammation

“…The metabolic complications of atherosclerosis have directed attention toward peroxisome proliferatorsactivated receptors (PPARs) as antiinflammatory molecules involved in the vascular wall (11,12). Activation of PPARα with specific agonist represses AP-1 signaling in response to proinflammatory stimuli in ECs (13,14). It was not clear whether PPARα plays a role in modulating OSS-induced endothelial inflammation.…”