Alpha-Lipoic Acid Protects Human Aortic Endothelial Cells Against H 2 O 2 -Induced Injury and Inhibits Atherosclerosis in Ovariectomized Low Density Lipoprotein Receptor Knock-Out Mice

Background/Aims: Diseases caused by atherosclerosis are the leading causes of death in postmenopausal women, owing to the loss of estradiol. Hormone replacement therapy (HRT) provides short-term beneficial effects in the treatment of cardiovascular disease for postmenopausal women but may increase the risk of stroke and gynecological cancer. Therefore, a substitute for HRT is urgently in needed. Methods: In this study, we examined the effectiveness of alpha-lipoic acid (ALA), a natural potent antioxidant, in preventing the development and progression of atherosclerosis in the low density lipoprotein receptor deficient ( Ldlr-/- ) mouse model, using western blot analysis, immunohistochemistry, Oil-red-O, elastin staining and TUNEL assay. We also examined the protective effect of ALA in human aortic endothelial cells (HAECs) against H 2 O 2 -induced oxidative injury, using western blotting, immunofluorescence staining, and monocyte adhesion assay. Results: We showed that ALA treatment significantly reduced the atherosclerosis induced by ovariectomy and high fat diet in the Ldlr-/- mouse model and restored expression of estrogen receptors (ERα and ERβ), which reduced the progression of atherosclerosis. Moreover, ALA treatment attenuated monocyte adhesion, suppressed cellular apoptosis, and eliminated excessive generation of intracellular reactive oxygen species (ROS) by reducing the protein levels of ROS-generating enzymes Nox4 and p22phox, as well as inhibiting NF-κB activation in HAECs stimulated by H 2 O 2 . Conclusions: ALA could provide a potential treatment for atherosclerosis in postmenopausal patients.