Endothelial cell senescence: A core mechanism in the development of cardiovascular metabolic diseases.

Abstract

Endothelial cells (ECs), as integral components of the vascular intima, play a pivotal role in the regulation of vascular tone, maintenance of blood flow homeostasis, and control of inflammatory responses. In response to pathological insults such as oxidative stress, mitochondrial dysfunction, and persistent inflammatory stimulation, ECs undergo senescence-associated phenotypic transitions, characterized by cell cycle arrest, endothelial dysfunction, and the establishment of a chronic pro-inflammatory microenvironment. Senescent ECs exacerbate inflammatory signaling, impair vascular homeostasis, and reshape intercellular communication networks, thereby constituting a fundamental pathological mechanism underlying the development and progression of cardiometabolic diseases, including atherosclerosis (AS), diabetes mellitus (DM), and hypertension (HTN). This review comprehensively summarizes the major triggers, molecular regulatory pathways, and functional consequences of endothelial cell senescence, with a particular focus on the central role of inflammation in mediating senescence-driven cardiometabolic disease progression. Furthermore, potential therapeutic strategies targeting endothelial cell senescence are briefly discussed, providing theoretical insights for the prevention and management of cardiometabolic disorders.