Background: Atherosclerosis, a chronic inflammatory condition characterized by the accumulation of lipid and fibrous elements in the arterial wall, is a major contributor to cardiovascular disease. This study aimed to investigate the regulation of apoptosis and cellular aging in human umbilical vein endothelial cells by Thousand and One Amino Acid Kinase 1 (TAOK1) via Cell division cycle 20 (CDC20) in the context of atherosclerosis.
Methods: The study evaluated the impact of TAOK1 on Oxidized low-density lipoprotein (ox-LDL)-induced changes in cell viability, angiogenesis, cell senescence, apoptosis, cell cycle arrest, and related signaling pathways in human umbilical vein endothelial cells (HUVECs) using Cell Counting Kit-8, β-galactosidase staining, flow cytometry, and western blot. The role of CDC20 as a potential downstream target of TAOK1 was further investigated using specific small interfering (si) RNAs.
Results: Overexpression of TAOK1 partially reversed the ox-LDL-mediated reduction in cell viability and counteracted the increase in pro-inflammatory cytokines and chemokines in HUVECs, with significant differences observed (p < 0.05). Ox-LDL-induced decrease in angiogenesis and increase in cell senescence, apoptosis were observed, and cell cycle arrest was alleviated by TAOK1, with all changes being statistically significant (p < 0.05). In addition, TAOK1 transfection partially neutralized ox-LDL-induced changes in key downstream pathway proteins, including CDC20, phosphorylated p65 (p-p65), β-catenin, and glycogen synthase kinase 3 beta (GSK-3β). Co-immunoprecipitation (Co-IP) confirmed the regulatory interaction between TAOK1 and CDC20. The inhibitory effects of TAOK1 on ox-LDL-induced cellular changes were significantly reversed by CDC20 siRNA (p < 0.05), highlighting the role of CDC20 in the protective mechanisms mediated by TAOK1.
Conclusions: TAOK1 plays a pivotal role in protecting endothelial cells from ox-LDL-induced cellular stress in the atherosclerotic environment, primarily by modulating pro-inflammatory responses, angiogenesis, cell senescence, and apoptosis. This study provides important insights into the protective mechanisms of TAOK1 and its interplay with downstream signaling molecules, particularly CDC20, in the vascular endothelium under atherosclerotic conditions.
Keywords: CDC20; HUVECs; NF-κB; TAOK1; Wnt/β-catenin; atherosclerosis.