Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Med Res Rev. 2023 Nov;43(6):2086-2114. doi: 10.1002/med.21970. Epub 2023 Apr 29.
The prevalence of cardiovascular disease (CVD) has been rising due to sedentary lifestyles and unhealthy dietary patterns. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor regulating multiple biological processes, such as lipid metabolism and inflammatory response critical to cardiovascular homeostasis. Healthy endothelial cells (ECs) lining the lumen of blood vessels maintains vascular homeostasis, where endothelial dysfunction associated with increased oxidative stress and inflammation triggers the pathogenesis of CVD. PPARα activation decreases endothelial inflammation and senescence, contributing to improved vascular function and reduced risk of atherosclerosis. Phenotypic switch and inflammation of vascular smooth muscle cells (VSMCs) exacerbate vascular dysfunction and atherogenesis, in which PPARα activation improves VSMC homeostasis. Different immune cells participate in the progression of vascular inflammation and atherosclerosis. PPARα in immune cells plays a critical role in immunological events, such as monocyte/macrophage adhesion and infiltration, macrophage polarization, dendritic cell (DC) embedment, T cell activation, and B cell differentiation. Cardiomyocyte dysfunction, a major risk factor for heart failure, can also be alleviated by PPARα activation through maintaining cardiac mitochondrial stability and inhibiting cardiac lipid accumulation, oxidative stress, inflammation, and fibrosis. This review discusses the current understanding and future perspectives on the role of PPARα in the regulation of the cardiovascular system as well as the clinical application of PPARα ligands.
由于久坐不动的生活方式和不健康的饮食模式，心血管疾病 (CVD) 的患病率一直在上升。过氧化物酶体增殖物激活受体 α (PPARα) 是一种核受体，调节多种生物学过程，如脂质代谢和炎症反应，这些过程对心血管稳态至关重要。健康的内皮细胞 (EC) 排列在血管腔的内壁，维持着血管稳态，而与氧化应激和炎症增加相关的内皮功能障碍会触发 CVD 的发病机制。PPARα 的激活可减少内皮炎症和衰老，有助于改善血管功能并降低动脉粥样硬化的风险。血管平滑肌细胞 (VSMC) 的表型转换和炎症会加剧血管功能障碍和动脉粥样硬化形成，而 PPARα 的激活可改善 VSMC 稳态。不同的免疫细胞参与血管炎症和动脉粥样硬化的进展。免疫细胞中的 PPARα 在免疫事件中发挥着关键作用，如单核细胞/巨噬细胞黏附和浸润、巨噬细胞极化、树突状细胞 (DC) 嵌入、T 细胞激活和 B 细胞分化。心肌细胞功能障碍是心力衰竭的一个主要危险因素，也可以通过激活 PPARα 来缓解，其通过维持心脏线粒体稳定性和抑制心脏脂质积累、氧化应激、炎症和纤维化来实现。本文讨论了目前对 PPARα 在调节心血管系统中的作用的理解和未来展望，以及 PPARα 配体的临床应用。
