Endothelium—The regulator of atherosclerosis

Atherosclerosis is a chronic, insidious, immune-inflammatory disease occurring in medium and large arteries, characterized by the accumulation of lipids within the vascular wall. Endothelial dysfunction has been confirmed as the core pathological link in the occurrence and development of atherosclerosis, closely related to multiple factors such as impaired endothelial barrier function, inflammation activation, cell death, oxidative stress, and abnormal adhesion molecules. It exerts a decisive influence on plaque formation, thrombus regulation, vascular tone, redox balance, and acute and chronic inflammatory responses. This review systematically elaborates on the multiple roles of endothelial cells in atherosclerosis, covering their physiological functions, pathological changes, and related molecular mechanisms. The article focuses on discussing the key roles of endothelial inflammation, various modes of cell death (apoptosis, necroptosis, pyroptosis, ferroptosis), endothelin system, eNOS/NO system, oxidative stress, non-coding RNA regulation, adhesion molecules, endothelial microparticles, endothelial glycocalyx, endothelial progenitor cells, endothelial–mesenchymal transition, physical exercise, and hemodynamics with endothelial mechanotransduction in endothelial dysfunction. In addition, the review analyzes the risk factors of atherosclerosis and summarizes current therapeutic strategies targeting endothelial dysfunction, including various drug interventions and lifestyle adjustments. It suggests that targeting endothelial injury pathways—particularly related cytokines and physical-chemical factors—may become a new avenue for the treatment of atherosclerosis. Future research should focus on the precise regulation and early intervention of endothelial-specific pathways. This paper aims to comprehensively clarify the regulatory mechanisms of the endothelium in atherosclerosis, providing a theoretical basis and new insights for the prevention and treatment of the disease.