Both estrogen and hydrogen sulfide (H2S) have been shown to inhibit the development of atherosclerosis. We previously reported that cystathionine gamma-lyase knockout (CSE-KO) male mice develop atherosclerosis earlier than male wide-type (WT) mice. The current study investigated the interaction of CSE/H2S pathway and estrogen on the development of atherosclerosis in female mice. Plasma estrogen levels were significantly lower in female CSE-KO mice than in female WT mice. NaHS treatment had no effect on plasma estrogen levels in both WT and CSE-KO female mice. After feeding CSE-KO and WT female mice with atheorgenic diet for 12 weeks, plasma lipid levels were significantly increased and triglyceride levels decreased compared with those of control diet-fed mice. Atherogenic diet induced more atherosclerotic lesion, oxidative stress, more intra-cellular adhesion molecule-1 (ICAM-1) and nuclear factor kappa-B (NFκB) in CSE-KO mice than in WT mice. Estrogen treatement of atherogenic diet-fed WT mice attenuated hypercholesterolemia, oxidative stress, ICAM-1 expression and NFκB in WT mice, but not in atherogenic diet-fed CSE-KO mice. Furthermore, H2S production in both the liver and vascular tissues was enhanced by estrogen in WT mice, but not in CSE-KO mice. It is concluded that the anti-atherosclerotic effect of estrogen is mediated by CSE-generated H2S. This study provides new insights into the interaction of H2S and estrogen signaling pathways on the regulation of cardiovascular functions.
- Smooth muscle cells
- Hydrogen sulfide
- Oxidative stress
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology