Expression Of Akt And GSK3? In The Atrium Of Patients With Vavular Atrial Fibrillation

BackgroudAtrail Fibrillation(AF)is a serious challenge in the field of cardiovascular disease in the world.The incidence of AF is increasing year by year,and the number of AF patients in China will increase significantly.Atrial fibrillation can cause discomfort,high disability rate,affect the quality of life,and bring heavy economic burden.There are many causes of atrial fibrillation,almost all heart diseases can produce atrial fibrillation,such as valvular disease,coronary heart disease,cardiomyopathy and so on.The incidence of valvular atrial fibrillation accounts for 12.9%of patients with atrial fibrillation.Although researchers have never stopped studying the pathogenesis of AF,it is still unclear.Similarly,the pathogenesis of valvular atrial fibrillation is not clear.Atrial remodeling is a key point in the development and maintenance of atrial fibrillation.The patients with valvular fibrillation have atrial structural changes characterized by left atrial enlargement,myocardial ultrastructural changes,and myocardial fibrosis changes.However,the molecular biological mechanism that causes atrial remodeling is very complicated,and has always been a research hotspot.Calcineurin(CaN)is a Ca2+/calmodulin-dependent protein phosphatase,and activated nuclear factor of activated cells(NFAT)is a protein substrate of CaN.Previous studies have shown that the CaN-NFAT pathway is involved in the development of valvular atrial fibrillation.Many previous studies have found that NFAT can regulate the expression of genes related to myocardial hypertrophy.CaN-NFAT signaling pathway and GSK3?-NFAT signaling pathway are involved in the regulation of myocardial hypertrophy through NFAT.The two pathways have crossover and connection parts.Glycogen synthase kinase 3?(GSK3?),as a common and highly conserved silk/threonine phosphokinase,can inactivate NFAT,thereby inhibiting the transfer of NFAT into the nucleus,affecting its further effect.Protein kinase B(Akt/PKB)is a more classical regulatory molecule upstream of GSK3?,which can activate GSK3? and then participate in the regulation of downstream NFAT Therefore,we speculate that Akt and GSK3? proteins also participate in the occurrence of atrial fibrillation in patients with valvular disease by affecting NFAT.However,the protein expression of these two enzymes in the myocardium of patients with valvular disease AF has not been reported.Whether the Akt-GSK3?-NFAT pathway are involved in valvular atrial fibrillation is rarely reported.Therefore,this subject will study and observe thisObjectiveTo explore the relationship between Akt,GSK3? protein and the development of patients with valvular atrial fibrillation;The relationship between Akt-GSK3?-NFAT pathway and fibrillation combined with valvular disease.MethodsUp to 42 cases of heart valve disease that underwent heart valve surgery were selected in the present study.The patients were divided into 2 groups,including sinus rhythm(SR)group(n=18)and Atrial fibrillation(AF)group(n=24)based on their history and electrocardiogram reports before surgery.Echocardiography was used to measure the cardiac cavity size,and analyze cardial function.During the operation,the left atrial(left atrial appendage)tissue was taken with liquid nitrogen tank and transferred to-80? refrigerator for experiment.Observe the protein expression of total Akt,p-Akt(activated form),total GSK3 ?,and p-GSK3?(non-activated form)by immunohistochemical technique.Western-blot technology was used to investigate the protein expression levels of total Akt,p-Akt,total GSK3?,and p-GSK3? in left atrium tissue.Besides,GAPDH was used as an internal standard.Results1.Compared with sinus rhythm group,the expression of p-Akt,total-GSK3? and p-GSK3 ? protein in cardiocyte endochylema of AF group was significantly increased;Total Akt protein was positive in both groups.2.Compared with the sinus rhythm group,the levels of p-Akt,total-GSK3 ? and p-GSK3 ? in myocardial cells of AF group were increased(P<0.05).There was no significant difference in total-Akt between the two groups3.Regardless of immunohistochemistry or Western-blot technology,you can see increased expression of activated Akt and increased non-activated GSK3? in atrial fibrillation.The level of total-GSK3? is also increased compared with the sinus rhythm group.Theoretically,total-GSK3? remains constant.So we analyze it may be related to the different course of the patient's atrial fibrillation.Some studies have found that the expression level of GSK3? presents a "mountain-like" change over time.ConclusionThe results suggest that Akt and GSK3? may be involved in the development of VF.