Peroxisome proliferator-activated receptors in the modulation of the immune/inflammatory response in atherosclerosis.
Inflammation has been recognized as an important hallmark of atherosclerosis. The pharmacological activation of PPAR-gamma by the thiazolidinediones in diabetes, and of PPAR-alpha 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-kappaB 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.
Fernandez
Ana Z
AZ
Laboratorio de Hemostasia y Genética Vascular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (I.V.I.C.), 1020 Caracas, Venezuela.