Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease.
Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease.
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DOI：
10.2217/fca.10.86
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发表时间：
2010-09
影响因子：
1.7
通讯作者：
Azhar S
中科院分区：
文献类型：
--
作者：
Azhar S
代谢综合征(METS)是一系列危险因素，包括胰岛素抵抗、中心性肥胖、血脂异常和高血压，这些因素显著增加了患2型糖尿病(T2 DM)和心血管疾病(CVD)的风险。过氧化物酶体增殖物激活受体亚型α、δ/β和γ是配体激活的核转录因子，调节一系列基因的表达，这些基因在调节糖、脂和胆固醇代谢方面发挥核心作用，失衡可导致肥胖、2型糖尿病和心血管疾病。它们也是药物靶点，目前，PPARα(贝特类)和PPARγ(噻唑烷二酮)激动剂分别用于临床治疗血脂异常和T2 DM。PPAR的这些代谢特征，加上它们参与代谢性疾病，意味着全世界正在进行广泛的努力，以开发基于PPAR的新的有效疗法，用于治疗与MET相关的其他疾病。本文综述了三种PPAR亚型的功能特点，讨论了PPAR在血管系统中的不同生物学作用的最新研究进展，并总结了用于临床治疗甲硫氨酸、2型糖尿病和心血管疾病关键成分的单、双、PAN(多)和部分PPAR激动剂的发展状况。它还总结了各种临床试验的临床结果，这些试验旨在评估目前使用的贝特类和噻唑烷二酮类药物的动脉粥样硬化保护作用。
Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones.