Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China.
Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China.
Int J Biol Macromol. 2023 Jul 1;242(Pt 2):125008. doi: 10.1016/j.ijbiomac.2023.125008. Epub 2023 May 20.
Atherosclerosis, a chief pathogenic factor of cardiovascular disease, is associated with many factors including inflammation, dyslipidemia, and oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are widely expressed with tissue- and cell-specificity. They control multiple genes that are involved in lipid metabolism, inflammatory response, and redox homeostasis. Given the diverse biological functions of PPARs, they have been extensively studied since their discovery in 1990s. Although controversies exist, accumulating evidence have demonstrated that PPAR activation attenuates atherosclerosis. Recent advances are valuable for understanding the mechanisms of action of PPAR activation. This article reviews the recent findings, mainly from the year of 2018 to present, including endogenous molecules in regulation of PPARs, roles of PPARs in atherosclerosis by focusing on lipid metabolism, inflammation, and oxidative stress, and synthesized PPAR modulators. This article provides information valuable for researchers in the field of basic cardiovascular research, for pharmacologists that are interested in developing novel PPAR agonists and antagonists with lower side effects as well as for clinicians.
动脉粥样硬化是心血管疾病的主要致病因素，与炎症、血脂异常和氧化应激等多种因素有关。过氧化物酶体增殖物激活受体 (PPAR) 是核受体，具有组织和细胞特异性的广泛表达。它们控制涉及脂质代谢、炎症反应和氧化还原平衡的多种基因。鉴于 PPAR 的多种生物学功能，自 20 世纪 90 年代发现以来，它们已被广泛研究。尽管存在争议，但越来越多的证据表明 PPAR 激活可减轻动脉粥样硬化。最近的进展对于理解 PPAR 激活的作用机制很有价值。本文综述了 2018 年至今的最新发现，主要包括调节 PPAR 的内源性分子、PPAR 在动脉粥样硬化中的作用，重点关注脂质代谢、炎症和氧化应激，以及合成的 PPAR 调节剂。本文为基础心血管研究领域的研究人员、对开发副作用更低的新型 PPAR 激动剂和拮抗剂感兴趣的药理学家以及临床医生提供了有价值的信息。
