F022 Healing of coronary endothelium by chronic 17beta-estradiol after ischemia/reperfusion injury in mice

Abstract

Endothelial protective actions of estrogens have been observed in various cardiovascular pathophysiological states. In particular, we showed that chronic 17beta-estradiol (E2) treatment prevents acute ischemia/reperfusion-induced coronary endothelial dysfunction in mice and accelerates reendothelialization after carotid injury. Whether such an endothelial healing effect occurs in a context of chronic reperfusion is unknown. Figure options Download full-size image Download as PowerPoint slide Thus, ischemia was induced by a left anterior descending coronary ligation for 30 minutes followed by one month of reperfusion (IR) in ovariectomized (OVX) mice, implanted or not 24 hours after ischemia (in order to avoid any effect on ischemic and/or early reperfusion injury) with an E2-releasing pellet (80 μg/kg/day). Coronary segments (internal diameter 180 to 220 μm) were removed distal to the site of occlusion and mounted in a wire myograph to study the relaxing response to acetylcholine (Ach). At 24 hours reperfusion (i.e. immediately before the onset of E2 treatment), OVX mice displayed a marked endothelial dysfunction (maximal relaxation to Ach: sham 55+/-4; IR 31+/-4 %; p<0.05). One month after reperfusion, untreated OVX mice showed a persistent decreased relaxation, whereas chronic E2 markedly increased the relaxing responses in IR mice (to a level similar to that of untreated sham mice) (Figure). E2 also slightly increased the relaxing responses in sham mice. In vitro NO Synthase inhibition abolished the differences between mice, suggesting that E2 restored the decreased NO production induced by IR. We thus demonstrate for the first time a marked beneficial effect of E2 on coronary endothelial healing after chronic reperfusion, leading to a restoration of coronary endothelial function.