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Pleiotropic Actions of PPARg Activators Thiazolidinediones in Cardiovascular Diseases

Author(s): Hiroyuki Takano, Hiroshi Hasegawa, Yunzeng Zou, Issei Komuro.

Abstract:

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 α, β (or δ), and γ. Although PPARγ is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrated that PPARγ is present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D2 (PGD2) metabolite, 15-deoxy-Δ12, 14- prostaglandin J2 (15d-PGJ2), are well-known as ligands for PPARγ. After it has been reported that activation of PPARg suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPARg have grown and a huge research effort has been concentrated. PPARg, is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimers disease. Moreover, PPARγ 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 PPARγ seems to have beneficial effects on atherosclerosis and heart failure, the mechanisms by which PPARγ ligands prevent the development of cardiovascular diseases are not fully understood. This review will focus on the latest developments in the PPARγ field and the roles of PPARg-dependent pathway in cardiovascular diseases.

Keywords: atherosclerosis, cardiac hypertrophy, glitazones, heart failure, myocardial infarction, th1/th2, thiazolidinedione

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Article Details

VOLUME: 10
ISSUE: 22
Year: 2004
Page: [2779 - 2786]
Pages: 8
DOI: 10.2174/1381612043383719
Price: $58