Pleiotropic actions of PPARγ activators thiazolidinediones in cardiovascular diseases

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor. To date, three PPARs 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. it has been recently demonstrated that PPARgamma is present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D-2 (PGD(2)) metabolite, 15-deoxy-Delta(12,) (14)-prostaglandin J(2) (15d-PGJ(2)), are well-known as ligands for PPARgamma. After it has been reported that activation of PPARgamma suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPARgamma have grown and a huge research effort has been concentrated. 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. Moreover, PPARgamma ligands have potent tumor modulatory effects against colorectal, prostate, and breast cancers. Recent 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 atherosclerosis and heart failure, the mechanisms by which PPARgamma ligands prevent the development of cardiovascular diseases are not fully understood. This review will focus on the latest developments in the PPARgamma field and the roles of PPARgamma-dependent pathway in cardiovascular diseases.