Takano Hiroyuki, Komuro Issei
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
Circ J. 2009 Feb;73(2):214-20. doi: 10.1253/circj.cj-08-1071. Epub 2009 Jan 8.
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.
过氧化物酶体增殖物激活受体（PPARs）是核受体超家族的成员，可与视黄酸X受体形成异二聚体。已分离出三种PPAR亚型，分别称为α、β（或δ）和γ。尽管PPARγ主要在脂肪组织中表达，并与脂肪细胞分化和葡萄糖稳态相关，但PPARγ也存在于多种细胞类型中。合成抗糖尿病噻唑烷二酮类药物（TZDs）是众所周知的PPARγ配体和激活剂。在有报道称激活PPARγ可抑制活化巨噬细胞中促炎细胞因子的产生后，人们对PPARγ的医学兴趣日益增加，并且进行了大量的研究工作。目前已知PPARγ与多种人类慢性疾病有关，如糖尿病、动脉粥样硬化、类风湿性关节炎、炎症性肠病和阿尔茨海默病。许多研究表明，TZDs不仅能改善胰岛素敏感性，还对许多组织和细胞类型具有多效性作用。尽管激活PPARγ似乎对心血管疾病有有益作用，但其配体预防心血管疾病发生发展的机制尚未完全明确。本文将讨论PPARγ依赖性途径在心血管疾病中的作用及其机制的最新数据。
