| First Author | Li H | Year | 2015 |
| Journal | J Mol Cell Cardiol | Volume | 87 |
| Pages | 92-101 | PubMed ID | 26271712 |
| Mgi Jnum | J:251206 | Mgi Id | MGI:6101809 |
| Doi | 10.1016/j.yjmcc.2015.08.008 | Citation | Li H, et al. (2015) Estradiol mediates vasculoprotection via ERRalpha-dependent regulation of lipid and ROS metabolism in the endothelium. J Mol Cell Cardiol 87:92-101 |
| abstractText | The estrogen-mediated vasculoprotective effect has been widely reported in many animal studies, although the clinical trials are controversial and the detailed mechanisms remain unclear. In this study, we focused on the molecular mechanism and consequence of 17beta-estradiol (E2)-induced ERRalpha (estrogen-related receptor alpha) expression in endothelium and its potential beneficial effects on vascular function. The human aorta endothelial cells were used to identify the detailed molecular mechanism and consequences for E2-induced ERRalpha expression through estrogen receptors (ER), where ERalpha responses E2-induced ERRalpha activation, and ERbeta responses basal ERRalpha expression. E2-induced ERRalpha expression increases fatty acid uptake/oxidation with increased mitochondrial replication, ATP generation and attenuated reactive oxygen species (ROS) formation. We have obtained further in vivo proof from high-fat diet mice that the lentivirus-carried endothelium-specific delivery of ERRalpha expression on the vascular wall normalizes E2 deficiency-induced increased plasma lipids with ameliorated vascular damage. ERRalpha knockdown worsens the problem, and the E2 could only partly restore this effect. This is the first time we report the detailed mechanism with direct evidence that E2-induced ERRalpha expression modulates the fatty acid metabolism and reduces the circulating lipids through endothelium. We conclude that E2-induced ERRalpha expression in endothelium plays an important role for the E2-induced vasculoprotective effect. |
