Peroxisome Proliferator-Activated Receptor .GAMMA. and Cardiovascular Diseases

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and form heterodimers with retinoid X receptor. Three PPAR isoforms have been isolated and termed alpha, beta (or delta) and gamma. Although PPARgamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARgamma is also present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) are well known as ligands and activators for PPARgamma. After it was reported that activation of PPARgamma suppressed production of pro-inflammatory cytokines in activated macrophages, medical interest in PPARgamma has grown and there has been a huge research effort. PPARgamma is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Many studies suggest that TZDs not only ameliorate insulin sensitivity, but also have pleiotropic effects on many tissues and cell types. Although activation of PPARgamma seems to have beneficial effects on cardiovascular diseases, the mechanisms by which PPARgamma ligands prevent their development are not fully understood. Recent data about the actions and its mechanisms of PPARgamma-dependent pathway in cardiovascular diseases are discussed here.