Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways

作者：Xiao Liang, Jingyuan Zhang, Jiangbo Yu, Jiyi Zhao, Shu-sen Yang · 发表于：European journal of medical research · 年份：2025 · DOI：10.1186/s40001-025-02562-y · 被引用次数：16 · 研究领域：Telomeres, Telomerase, and Senescence、Antioxidant Activity and Oxidative Stress、Adipokines, Inflammation, and Metabolic Diseases

Atherosclerosis (AS), a chronic inflammatory disease of the arterial wall, remains a dominant cause of death and disability globally. Quercetin has been evidenced to be effective against AS, but the exact mechanisms are still largely unclear. Oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) and mouse RAW264.7 macrophages were established, with quercetin treatment or p16, p21 or SERPINE1 siRNA transfection. Cellular senescence was assessed by SA-β-gal staining and detection of cellular senescence markers. Cell cycle, apoptosis and intracellular ROS were detected by flow cytometry, with cell proliferation by CCK-8. Lipid accumulation was assessed utilizing oil red O staining. Through transmission electron microscope, autophagosomes and mitochondria were investigated, with detection of autophagy markers. Finally, AS models of ApoE −/− mice were established through feeding high-fat diet, and the effect of quercetin on alleviating AS progression was investigated. Quercetin protected HAECs from ox-LDL-elicited senescent phenotype, growth arrest and apoptosis and promoted cell viability in a concentration-dependent fashion. Furthermore, quercetin alleviated ox-LDL-elicited cellular senescence, ROS and lipid accumulation in macrophages. In ox-LDL-induced HAECs or/and macrophages, quercetin down-regulated the expression of p16, p21, p53 and SERPINE1, elevated p-AMPK/AMPK levels and decreased p-mTOR/mTOR levels, and these effects of quercetin wer...