Abstract P100: Inhibition of Mitochondrial Permeability Transition Pore Opening by Activation of GPR-30 Provides Heart Protection Against Ischemia-Reperfusion Injury
Introduction: Most biological effects of estrogen are mediated by classical estrogen receptors, alpha (ERα) and beta (ERβ). Recently, several studies in vitro have demonstrated a novel G protein coupled receptor 30 (GPR-30) which can also bind directly to estrogen and mediate estrogen action. The goals of this study are to define the role of GPR-30 activation with a specific agonist G1 in ischemic myocardial injury and to identify the molecular mechanisms that mediate these effects.
Methods: Hearts of male mice were isolated and retrograde-perfused through aorta with the Langendorff system at 37°C. After 20 min of perfusion, hearts were subjected to 20min global normothermic ischemia followed by 40min reperfusion. Hearts were perfused with Krebs Henseleit (KH) solution or KH+G1(1μM) oxygenated with 95% O2 and 5% CO2. After the reperfusion, infarct size was evaluated by triphenyltetrazolium chloride (TTC) staining and the heart function recovery was measure using a Power Lab (ADInstruments). The LV systolic pressures, the LV end-diastolic pressure, the heart rate, the maximum velocity of contraction dP/dt max and relaxation dP/dt min were recorded. Mitochondria were isolated to measure Calcium Resistance Capacity (CRC) after 10min of reperfusion.
Results: Heart treated with G1 had increased Calcium Retention capacity (1.6±0.11μM vs. 2.4±0.06, p<0.01), a reduced infarct size (21±2% vs. 46±3%, p<0.001), and all heart functional parameters were improved in G1 treated group compared to control group.
Conclusion: These results indicate that the activation of GPR-30 lead to the inhibition of the mPTP opening and provides a cardioprotective effect against ischemia-reperfusion injury.