Zhong Jixin, Kankanala Saumya, Rajagopalan Sanjay
Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA *Jixin Zhong and Sanjay Rajagopalan contributed equally to the writing of this article.
Curr Opin Lipidol. 2016 Oct;27(5):484-92. doi: 10.1097/MOL.0000000000000340.
Atherosclerosis is the leading cause of death globally. The pathophysiology of atherosclerosis is not fully understood. Recent studies suggest dipeptidyl peptidase-4 (DPP4), a regulator of inflammation and metabolism, may be involved in the development of atherosclerotic diseases. Recent advances in the understanding of DPP4 function in atherosclerosis will be discussed in this review.
Multiple preclinical and clinical studies suggest DPP4/glucagon-like peptide-1 axis is involved in the development of atherosclerotic disease. However, several recent trials assessing the cardiovascular effects of DPP4 inhibition indicate enzymatic inhibition of DPP4 lacks beneficial effects on cardiovascular disease.
Catalytic inhibition of DPP4 with DPP4 inhibitors alters pathways that could favor cardioprotection. Glucagon-like peptide-1 receptor-independent aspects of DPP4 function may contribute to the overall neutral effects on cardiovascular outcome seen in the outcome trials.
动脉粥样硬化是全球主要的死亡原因。动脉粥样硬化的病理生理学尚未完全明了。近期研究表明,作为炎症和代谢调节因子的二肽基肽酶4(DPP4)可能参与动脉粥样硬化疾病的发生发展。本综述将讨论对DPP4在动脉粥样硬化中功能的最新认识进展。
多项临床前和临床研究表明,DPP4/胰高血糖素样肽-1轴参与动脉粥样硬化疾病的发生发展。然而,近期几项评估DPP4抑制作用心血管效应的试验表明,对DPP4的酶抑制作用对心血管疾病并无有益影响。
使用DPP4抑制剂对DPP4进行催化抑制会改变可能有利于心脏保护的途径。DPP4功能中不依赖胰高血糖素样肽-1受体的方面可能是导致在结局试验中观察到对心血管结局总体无影响的原因。