Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development

作者：Wei-Li Wang, Yu‐Tsung Shih, Shu-Yi Wei, Jeng‐Jiann Chiu · 发表于：Journal of Biomedical Science · 年份：2025 · DOI：10.1186/s12929-025-01177-z · 被引用次数：42 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Cardiovascular Health and Disease Prevention、Adipokines, Inflammation, and Metabolic Diseases

Aging is the foremost risk factor for metabolic syndrome and atherosclerosis, which is a principal cause of cardiovascular diseases (CVDs). Vascular endothelial cells (ECs), which line the vascular intima, play a central role in maintaining vascular homeostasis. Their dysfunction, marked by impaired barrier function, inflammation, and metabolic dysregulation, constitutes an early and pivotal event in atherogenesis. As key sensors of hemodynamic forces, ECs are constantly exposed to blood flow-induced shear stress, which exert divergent effects on metabolism depending on the flow pattern. Laminar flow with relatively high shear stress (LS), as a critical atheroprotective factor, maintains EC quiescence and promotes anti-inflammatory responses and antioxidant defense, whereas disturbed flow with low and oscillatory shear stress (OS), induces the athero-susceptible signaling network to activate glycolysis and inflammation in ECs. While genetic, epigenetic, and molecular signaling mechanisms in EC physiology and pathophysiology have been extensively explored, the crucial role of EC metabolism in EC dysfunction and atherogenesis remains largely understudied. By serving as precursors, intermediates, and end products of cellular processes, metabolites offer a dynamic snapshot of endothelial metabolic states under both physiological and pathophysiological conditions. With aging, ECs undergo profound metabolic reprogramming, including disrupted glycolysis, mitochondrial dysfunction, a...