YAP Relieves Hypoxia-induced Apoptosis Of Myocardial Cells By Regulating Glut 1 And JNK

Objective: Acute myocardial infarction(AMI)has become a worldwide problem due to its high morbidity and mortality.Cardiomyocyte apoptosis is an important event of cell death in AMI.Yes-associated protein(YAP)is the downstream core effector in the Hippo pathway,which has been shown to relieve apoptosis in a variety of diseases,but the specific mechanism of YAP in regulating myocardial apoptosis in AMI has not been fully clarified.The purpose of this study was to investigate the regulatory effect and mechanism of YAP on myocardial apoptosis of AMI.Methods: AMI rats model was established by ligation of left anterior descending coronary artery with sham control which only threading without ligation,ECG monitoring was performed immediately after the operation,and the heart was euthanized and sectioned after 4 weeks of feeding.HE and Masson staining were used to evaluate the pathological changes of myocardial tissue,TUNEL staining was used to detect the apoptosis of myocardial tissue,and Western blot was used to detect the protein expression of YAP,Cleaved caspase 3,Bax,and Bcl-2 in myocardial tissue.H9C2 cells were cultured in vitro and H9C2 cells were infected with lentivirus to establish a stable infection strain with YAP overexpression and subjected to hypoxia treatment to construct a hypoxia model.Cell viability was detected by CCK8,apoptosis was detected by TUNEL staining,and the protein expressions of YAP,Glut1,JNK,p-JNK,Cleaved caspase 3,Bax,and Bcl-2 were detected by Western blot.Results: The ST segment of the electrocardiogram of the AMI rats model was significantly elevated after operation.HE staining showed that the myocardial tissue arrangement was disordered and the normal cell morphology disappeared.Masson staining showed obvious fibrosis.Apoptosis occurred in myocardial tissue,cleaved caspase 3 and Bax expression increased while Bcl-2 expression decreased(P < 0.01),and nuclear YAP protein level decreased(P < 0.01).After hypoxia treatment,compared with normal group,cell viability decreased and apoptosis increased in hypoxia group,cleaved caspase 3 and Bax expression increased while Bcl-2 expression reduced(P < 0.01),nuclear YAP and Glut1 protein expression decreased while p-JNK expression increased(P <0.01).Cell viability was increased and apoptosis was decreased in oe-YAP+ hypoxia group,and the expressions of Bcl-2 and Glut1 were increased,while the expressions of cleaved caspase 3,Bax and p-JNK were decreased(P < 0.01).Conclusion: 1.AMI rats and hypoxic H9C2 cells showed significant apoptosis and decreased YAP expression.2.Overexpression of YAP relieved hypoxia – induced cell apoptosis.3.YAP plays an anti-apoptotic role by regulating the expression of Glut1 and JNK.