Excessive
inflammation and the pyroptosis of vascular endothelial cells caused by
estrogen deficiency is one cause of
atherosclerosis in post-menopausal women. Because autophagy is highly regulated by
estrogen, we hypothesized that
estrogen can reduce vascular endothelial cell pyroptosis through
estrogen receptor alpha (ERα)-mediated activation of autophagy to improve
atherosclerosis in post-menopausal stage. Aortic samples from pro-menopausal and post-menopausal women with ascending aortic
arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female
ApoE-/- mice and
homocysteine (Hcy)-treated HUVECs were used to analyze the effect of
estrogen supplementation
therapy. The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in
inflammation and pyroptosis in female post-menopausal patients.
Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX
ApoE-/- mice and Hcy-treated HUVECs.
Estrogen had
therapeutic effect on
atherosclerosis and improved the symptoms associated with
lipid metabolism disorders in OVX
ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of
estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of
estrogen, but had no influence on ERα expression. Thus, the results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that
estrogen prevents
atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce
inflammation and pyroptosis.