Post-ischemic GPER1 Activation Induces Cardioprotective Effects Against Ischemia/Reperfusion Injury By Inhibiting Apoptosis

BackgroundIn 2012,cardiovascular diseases killed 17.5 million people.Of these,7.4 million people died of ischemic heart disease and 6.7 million from stroke.So the methods to treat the ischemic heart disease have become more and more important.But in clinical treatment,people found that if the ischemic tissue is reperfused with blood,the damage dose not decrease,but increase.This is called ischemia reperfusion injury?I/R injury?.The mechanism of I/R injury is relation to ROS production,Ca²⁺ overload,inflammation and decrease of ATP production.And I/R injury can induce cell death,which are included apoptosis,autophagy and necrosis.So in myocardial I/R injury,detect the methods to inhibit cell apoptosis has become the primary way to decrease the injury of myocardial I/R.ObjectiveThis study showed that post-ischemic estrogen treatment induces cardioprotective effects against I/R injury through GPER1 activation by inhibiting activation of Caspase-3and Caspase-9.And activation of GPER1 also can inhibit cytochrome C release from mitochondria.MethodsMale Sprague-Dawley rats were used.Hearts were subjected to 35 min of the left anterior descending artery occlusion followed by 120 min reperfusion.An estrogen?50ug/kg?or PBS?same volume?was applied via the femoral vein 5 min before reperfusion,and GPER1 antagonist,G15?1.5mg/kg?,given 10 min before estrogen.Area at risk?AAR?was identified using Evans Blue dye and myocardial infarct size assessed by TTC staining.LDH and CK were checked after ischemia reperfusion injury.Caspase-3 and Caspase-9activation was checked and the qualitity of mitochondria was checked by electron microscope.The release of cytochorome C was checked by western blot.ResultsIn rat heart I/R injury,we found that post ischemia-E2 treatment reduced myocardial infarct size normalized to the AAR or to the whole LV and inhibited LDH and CK release.We also found that post ischemia-E2 treatment inhibited the activation of caspase-3 and caspase-9.And activation of GPER1 can inhibit cytochrome C release from mitochondria.The protective role of E2 in I/R was blocked by G15.ConclusionsPI-E2 treatment induces cardioprotective effects against I/R injury via GPER1 activation.PI-E2 effects through GPER1 involve inhibition of apoptosis.