School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
Int J Mol Sci. 2023 Oct 13;24(20):15160. doi: 10.3390/ijms242015160.
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
内皮细胞（ECs）构成血管的内层，直接暴露于循环系统中的内源性危险信号和代谢物。ECs 的衰老和死亡不仅是不良后果，也是内皮功能障碍的因果贡献者，内皮功能障碍是动脉粥样硬化的早期风险标志物。EC 衰老的病理生理过程涉及结构和功能的变化，并与多种因素有关，包括氧化应激、细胞周期失调、高尿酸血症、血管炎症和代谢物感知和信号异常。动脉粥样硬化中已经记录了多种形式的 EC 死亡，包括自噬细胞死亡、细胞凋亡、细胞焦亡、NETosis、坏死性凋亡和铁死亡。尽管如此，动脉粥样硬化中 EC 衰老或死亡的分子机制仍不完全清楚。为了提供该主题的全面更新，本综述检查了与动脉粥样硬化不同阶段的 EC 衰老和死亡相关的分子机制和功能改变的历史和最新发现。
