COX7C alleviates lipid accumulation and apoptosis in hyperlipidemia models via HIF-1α pathway

Introduction Background: One of the main contributing factors to the growth of atherosclerosis is hyperlipidemia (HLP). COX7C is a mitochondrial protein that is essential to mitochondrial function and cellular homeostasis. However, its role in hyperlipidemia and atherosclerosis remains underexplored. Aim: To look into the function of COX7C in lipid accumulation, mitochondrial function, and apoptosis in a hyperlipidemia model, explore its mechanism of action through the HIF-1α pathway. Material and methods Bioinformatics analysis of the GSE13985 dataset was performed, and COX7C was selected as a hub gene. Free fatty acids were utilized to treat HepG2 cells to establish a hyperlipidemia model. Lipid buildup was assessed by oil red O (ORO) staining, and cholesterol ester levels, adenosine triphosphate content, and reactive oxygen species (ROS) levels were quantified by kit assays. Western blot (WB), flow cytometry, and CCK-8 were utilized to assess protein expression levels, cell viability, and apoptosis. The effects of HIF-1α inhibition were investigated using the HIF-1α inhibitor KC7F2. Results Overexpression of COX7C significantly reduced lipid accumulation, improved cell viability, and alleviated mitochondrial damage in a hyperlipidemia model. Flow cytometry and WB research on apoptosis-related proteins demonstrated that COX7C overexpression also reduced ROS production and inhibited apoptosis. In addition, COX7C overexpression activated the HIF-1α pathway, further alleviating mitochondrial damage and apoptosis. KC7F2 reversed the protective effect of COX7C, indicating that COX7C acts through HIF-1α in the context of hyperlipidemia. Conclusions COX7C reduces lipid accumulation and apoptosis in a hyperlipidemia model by activating the HIF-1α pathway, may provide a therapeutic strategy for atherosclerosis.