Smoking upregulates HMOX1 expression to promote atherosclerosis by inducing ferroptosis in coronary artery endothelial cells

Atherosclerosis (AS) is a common chronic cardiovascular disease that can be caused by various factors. Smoking is a significant risk factor for AS, but its mechanisms are not yet clear. HMOX1 (heme oxygenase 1) has shown abnormal expression levels in cardiovascular diseases. Whether HMOX1 is related to smoking-induced AS remains unknown. This study focuses on the intrinsic relationship between AS and smoking, particularly the specific role of HMOX1 in this process, thereby providing new theoretical support for the treatment of AS. In vivo and in vitro experiments were conducted to investigate the effects of smoking on AS and aortic ferroptosis. Bioinformatics was used to explore the changes in HMOX1 in coronary artery endothelial cells before and after smoking. CCK8, colony formation assays, and flow cytometry were used to detect the effects of nicotine treatment and Ferrostatin-1 on human coronary artery endothelial cells (HCAECs) proliferation and apoptosis. ELISA and Western blotting were used to detect changes in ferroptosis markers in HCAECs after the addition of Ferrostatin-1 or transfection of siHMOX1 . Smoking increased atherosclerotic plaques in the aortas of mice, with severe lipid deposition. HMOX1 expression was elevated in smoking-induced coronary endothelial cells. Smoking induced ROS, lipid ROS, Fe 2+ , MDA concentrations, PTGS2 expression and decreased GSH concentration, GPX4, SLC7A11 expression both in vitro and in vivo, consistent with ferroptosis. Nicotine treatment reduced the proliferation and accelerated the apoptosis of HCAECs, while knocking down HMOX1 could rescue these changes. HMOX1 is highly expressed in smoking-induced coronary artery endothelial cells and promotes AS by regulating ferroptosis.