PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets

作者：Yi Zheng, Mingyan Shao, Yanfei Zheng, Wenlong Sun, Si Qin, Ziwei Sun, Linghui Zhu, Yuanyuan Guan, Qi Wang, Yong Wang, Lingru Li · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.03.020 · 被引用次数：36 · 研究领域：Peroxisome Proliferator-Activated Receptors、Cardiovascular Disease and Adiposity、Cancer Research and Treatment

BACKGROUND: Atherosclerosis is a chronic and complex disease caused by lipid disorder, inflammation, and other factors. It is closely related to cardiovascular diseases, the chief cause of death globally. Peroxisome proliferator-activated receptors (PPARs) are valuable anti-atherosclerosis targets that showcase multiple roles at different pathological stages of atherosclerosis and for cell types at different tissue sites. AIM OF REVIEW: Considering the spatial and temporal characteristics of the pathological evolution of atherosclerosis, the roles and pharmacological and clinical studies of PPARs were summarized systematically and updated under different pathological stages and in different vascular cells of atherosclerosis. Moreover, selective PPAR modulators and PPAR-pan agonists can exert their synergistic effects meanwhile reducing the side effects, thereby providing novel insight into future drug development for precise spatial-temporal therapeutic strategy of anti-atherosclerosis targeting PPARs. KEY SCIENTIFIC: Concepts of Review: Based on the spatial and temporal characteristics of atherosclerosis, we have proposed the importance of stage- and cell type-dependent precision therapy. Initially, PPARs improve endothelial cells' dysfunction by inhibiting inflammation and oxidative stress and then regulate macrophages' lipid metabolism and polarization to improve fatty streak. Finally, PPARs reduce fibrous cap formation by suppressing the proliferation and migration of vas...