Apolipoprotein C3-Rich Low-Density Lipoprotein Induces Endothelial Cell Senescence via FBXO31 and Its Inhibition by Sesamol In Vitro and In Vivo

• Published in: Biomedicines Vol. 10; no. 4; p. 854
• Main Authors: Tsai, Ping-Hsuan, Chen, Li-Zhen, Tseng, Kuo-Feng, Chen, Fang-Yu, Shen, Ming-Yi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.04.2022; MDPI
• Subjects: Aging; Antibodies; Antioxidants; Aortic arch; apolipoprotein C3-rich LDL; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Cardiovascular disease; Cardiovascular diseases; Cell cycle; Coronary vessels; Deoxyribonucleic acid; DNA; DNA damage; Endothelial cells; Endothelium; FBXO31; High fat diet; Ischemia; Lipids; Lipoproteins; Low density lipoprotein; Plasma; premature endothelial senescence; Proteins; Senescence; sesamol; Stroke; Therapeutic applications; Therapeutic targets; United States > US; Japan; Taiwan; atherosclerosis; premature endothelial senescence; sesamol; apolipoprotein C3-rich LDL; FBXO31
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10040854

Premature endothelial senescence decreases the atheroprotective capacity of the arterial endothelium. Apolipoprotein C3 (ApoC3) delays the catabolism of triglyceride-rich particles and plays a critical role in atherosclerosis progression. FBXO31 is required for the intracellular response to DNA damage, which is a significant cause of cellular senescence. Sesamol is a natural antioxidant with cardiovascular-protective properties. In this study, we aimed to examine the effects of ApoC3-rich low-density lipoprotein (AC3RL) mediated via FBXO31 on endothelial cell (EC) senescence and its inhibition by sesamol. AC3RL and ApoC3-free low-density lipoproteins (LDL) (AC3(-)L) were isolated from the plasma LDL of patients with ischemic stroke. Human aortic endothelial cells (HAECs) treated with AC3RL induced EC senescence in a dose-dependent manner. AC3RL induced HAEC senescence via DNA damage. However, silencing FBXO31 attenuated AC3RL-induced DNA damage and reduced cellular senescence. Thus, FBXO31 may be a novel therapeutic target for endothelial senescence-related cardiovascular diseases. Moreover, the aortic arch of hamsters fed a high-fat diet with sesamol showed a substantial reduction in their atherosclerotic lesion size. In addition to confirming the role of AC3RL in aging and atherosclerosis, we also identified AC3RL as a potential therapeutic target that can be used to combat atherosclerosis and the onset of cardiovascular disease in humans.