Liao Hai-Han, Jia Xu-Hui, Liu Huang-Jun, Yang Zheng, Tang Qi-Zhu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Cardiovascular Research Institute of Wuhan University, Wuhan, China.
Curr Pharm Des. 2017;23(11):1677-1686. doi: 10.2174/1381612822666160928150040.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in the regulation of lipid metabolism, energy production, and inflammation. It is well established that all of the three isoforms of PPARs expressed in the cardiomyocytes, and that PPARs are closely involved in the regulation of lipid metabolism and energy homeostasis as well as many other different aspects in the heart. We think that PPARs are very important therapeutic targets for drug development, however, the drugs targeting at PPARs meet some trouble in clinical practice, especially the reported side effects related to heart failure. This review summarizes different functions and mechanisms of each isoform in cardiac hypertrophy and heart failure, for the reason that if more efforts are made to investigate the interactions among different isoforms, minimize the off-target effects, and avoid PPARs-independent side effects, we can develop safer and more effective PPAR agonists for the clinical practice in the near future.
过氧化物酶体增殖物激活受体（PPARs）是配体激活的转录因子，参与脂质代谢、能量产生和炎症的调节。心肌细胞中表达的PPARs的所有三种亚型均已明确，并且PPARs密切参与心脏脂质代谢和能量稳态的调节以及心脏中许多其他不同方面。我们认为PPARs是药物开发的非常重要的治疗靶点，然而，靶向PPARs的药物在临床实践中遇到了一些问题，特别是报道的与心力衰竭相关的副作用。本综述总结了每种亚型在心肌肥大和心力衰竭中的不同功能和机制，原因在于如果能做出更多努力来研究不同亚型之间的相互作用，将脱靶效应降至最低，并避免与PPARs无关的副作用，那么在不久的将来我们就能开发出更安全、更有效的PPAR激动剂用于临床实践。
