Estradiol-17β inhibits homocysteine mediated damage by promoting H2 S production via upregulating CBS and CSE expression in human umbilical vein endothelial cells.

Abstract

Associated with reduced hydrogen sulfide (H2 S) production in Hcy metabolic disorders, Plasma Hcy accumulation can bring about vascular dysfunction. Nevertheless, recently proposed therapies for vascular damage by estrogen could contribute to promoting endogenous hydrogen sulfide production. This study explores whether estrogen can come into play in protection in hyperhomocysteinemia and hypertensive patients at a population level, and then analyses the specific mechanism of estrogen protection in homocysteine (Hcy)-treated human umbilical vein endothelial cells (HUVECs) at the foundational level. A case-control study, conducted on 1277 female hypertension and non-hypertensive patients from Hunan Provincial People's Hospital, showed that the Hcy concentration of hypertensive patients emerged higher than that of healthy controls (P < .001), and that of estrogen was the reverse (P < .001). Estrogen had a negative correlation with systolic blood pressure and plasma Hcy concentration. HUVECs were treated with estrogen and Hcy in the basic experimental part, and 17β-estradiol (E2β) stimulated proliferation and inhibited damage in Hcy-treated umbilical vein endothelial cells. Treatment with Hcy dampens the expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) then cuts down H2 S production in cultured HUVECs, however, E2β reverses this process. To sum up, we have demonstrated a significant correlation between estrogen, Hcy concentration and systolic blood pressure reduction, which is bound up with Hcy metabolism and endogenous hydrogen sulfide production. The role of E2β was further strengthened by CBS and the CSE inhibitor through overthrowing the change in hydrogen sulfide of Hcy-treated HUVECs.