Correlation Study Between Atrial Fibrillation Patients And Caspase-8/Caspase-3/PARP-1 Signaling Pathway

Objective:The purpose of this study was to detect the expression levels of Caspase-8,cleaved-Caspase-3 and cleaved-PARP-1 in atrial fibrillation(AF)patients.To investigate the significance of Caspase-8/Caspase-3/PARP-1signaling pathway in atrial remodeling in patients with AF.Methods:A total of 148 AF patients from the cardiovascular Department of the First Affiliated Hospital of Bengbu Medical College were enrolled in the AF group,and 118 patients with sinus rhythm were enrolled in the SR group.Serum Caspase-8 and cleaved-PARP-1 activity levels were detected by ELISA.Protein expression levels of Caspase-8,cleaved-Caspase-3,cleaved-PARP-1 in PBMCS were detected by Western-blot analysis.Patients undergoing cardiac surgery in our hospital were also selected and divided into AF group(n=10)and SR group(n=10).A little atrial tissue was obtained intraoperatively and stained by HE.The collagen volume fraction(CVF)was calculated by MASSON staining.TUNEL staining was used to observe the difference of apoptosis between the two groups under fluorescence microscope.The protein expression levels of Caspase-8,cleaved-Caspase-3,cleaved-PARP-1 in atrial tissues were detected by Western-blot analysis,and the correlation between the indexes was analyzed.Result:1.There were no significant differences in age,sex,history of hypertension,history of diabetes and other general information between the atrial fibrillation group and the sinus rhythm group(P>0.05).There were no significant differences in peripheral blood white blood cell count(WBC),low density lipoprotein(LDL),high density lipoprotein(HDL),triglyceride(TG),serum creatinine(Scr),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)between the two groups(P>0.05).The results of color doppler ultrasound indicated that the left atrial diameter in atrialfibrillation group was higher than that in sinus rhythm group,and the differences were statistically significant(P<0.05).2.ELISA and WB results showed that serum Caspase-8 and cleaved PARP-1 levels were increased in the atrial fibrillation group compared with the sinus rhythm group(P<0.05).Protein expression levels of Caspase-8,cleaved-Caspase-3,cleaved-PARP-1 were increased in PBMCS and atrial tissues(P<0.05).3.Staining results showed that,compared with the sinus rhythm group,atrial myocyte structure was significantly damaged and myocardial fibrosis was aggravated in the atrial fibrillation group(P<0.05).Meanwhile,the apoptosis rate of atrial myocytes in atrial fibrillation group was significantly increased compared with that in sinus rhythm group(P<0.05).Meanwhile,the apoptosis rate of atrial myocytes in atrial fibrillation group was significantly increased compared with that in sinus rhythm group(P<0.05).4.Pearson correlation analysis: Serum Caspase-8 and cleaved PARP-1were positively correlated with LAD in the atrial fibrillation group(r=0.590,P<0.05;r=0.641,P<0.05);Caspase-8,cleaved-Caspase-3,cleaved-PARP-1were positively correlated with CVF and atrial cell apoptosis rate,respectively.Conclusion:1.Elevated levels of Caspase8,cleaved-PARP-1 in serum,and elevated levels of Caspase8,cleaved-Caspase3,cleaved-PARP-1 in PBMCS and atrial tissue may play a certain role in the occurrence of atrial fibrillation.2.In the atrial fibrillation group,the apoptosis of atrial muscle tissue was significantly increased,and the degree of myocardial fibrosis was aggravated.Atrial structural remodeling was associated with the occurrence of atrial fibrillation to a certain extent.3.Atrial myocyte apoptosis plays an important role in the process of atrial remodeling and fibrosis in atrial fibrillation,and its mechanism may be related to cell apoptosis mediated by Caspase-8/Caspase-3/PARP-1 signaling pathway.