Estrogen prevents homocysteine-induced endothelial dysfunction in porcine arteries

Abstract

Introduction: Hyperhomocysteinemia is an independent risk factor of atherosclerosis and thrombosis. Estrogen may have a cardioprotective effect by improvement of endothelial functions. Thus, we hypothesized that estrogen might protect endothelium from homocysteine damage. The objective of this study was to examine the effect of estrogen on homocysteine treated porcine coronary arteries. Methods: Pig coronary artery rings were incubated with homocysteine (50 μM), estrogen (10−5M), or homocysteine and estrogen (50 μM/10−5M) for 24 h. Myograph tension analysis was performed with thromboxane A2 analogue U46619 for contraction and bradykinin for endothelium dependent vasorelaxation or sodium nitroprusside for endothelium independent vasorelaxation. Results: There were no differences of maximal contraction in response to U46619 among all groups of porcine coronary artery rings. However, endothelium-dependent vasorelaxation was different. Homocysteine treated vessels showed 62% relaxation in response to 10−5M bradykinin, which was significantly reduced compared to control vessels (88% relaxation) (P<0.05). There was no significant difference of endothelium dependent vasorelaxation between estrogen treated and control groups (P>0.05). Furthermore, combining homocysteine and estrogen showed 75% improvement of endothelium dependent vasorelaxation as compared to homocysteine treatment alone. There was no difference in endothelium-independent vasorelaxation (sodium nitroprusside) between all groups. Conclusion: These data demonstrated that homocysteine significantly reduces endothelium dependent vasorelaxation, and estrogen significantly prevents homocysteine-mediated endothelial dysfunction in porcine coronary arteries. This study suggests that estrogen may be of benefit in the hyperhomocysteinemic patient.