Abstract 1613: Activation of a Novel Estrogen Receptor, GPR30, is Cardioprotective in the Rat
It has been well documented that pre-menopausal females have a lower incidence of cardiovascular disease than their male counterparts. However, post-menopausal women reach the rates of disease in men suggesting a protective role of estrogen. Numerous animal studies have also demonstrated that estrogen is cardioprotective. Historically, estrogen has been thought to signal through two nuclear receptors, ERa and ERb; however, a third, membrane bound receptor, GPR30, has been identified and shown to bind estrogen with high affinity. GPR30 is a G protein coupled receptor localized to the plasma membrane and endoplasmic reticulum. To date, there is little information on GPR30 in the heart and no study has looked at the effect of GPR30 activation during myocardial ischemia and reperfusion. Therefore, the goal of this study was to determine whether activation of GPR30 results in a cardioprotective phenotype in rats. A highly specific GPR30 agonist, G-1, was administered to Sprague Dawley (200–300g) rat hearts 10 minutes prior to 20 minutes of ischemia followed by 120 minutes of reperfusion using a Langendorff model. Recovery of post-ischemic function was significantly better in G-1 treated hearts compared to controls (39.4±5.5 vs 23.6±2.5% of pre-ischemic rate pressure product, p<0.05). Additionally, infarct size was reduced in the G-1 treated animals when compared to control (16.5±4.4 vs 30.6±3.3% p<0.05). The protection afforded by G-1 was blocked by co-administration of a PI3K inhibitor (wortmannin 100nM). Through western blot analysis, it was demonstrated that G-1 induced the activation of both Akt and Erk1/2 and was blocked by PI3K inhibition. Taken together, the data show that G-1 activation of GPR30 improved functional recovery and reduced infarct size in isolated rat hearts following ischemia and reperfusion through a PI3K dependent mechanism.