Targeting PPARs for therapy of atherosclerosis: A review

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.

Automated summary

Atherosclerosis, a major factor of cardiovascular disease, is influenced by inflammation, dyslipidemia, and oxidative stress. Peroxisome proliferator-activated receptors (PPARs), as nuclear receptors, have tissue- and cell-specific expression and regulate genes involved in lipid metabolism, inflammation, and redox homeostasis. Despite controversies, accumulating evidence supports the role of PPAR activation in attenuating atherosclerosis. Recent advances provide valuable insights into the mechanisms of PPAR activation.