Screening Of Risk Factors For Ischemic Cardiomyopathy And The Relationship Between Autophagy-related Proteins Beclin-1,BNIP3 And Ischemic Cardiomyopathy

Objective: 1.To study the risk factors of ischemic cardiomyopathy(ICM)and investigate the independent correlation between the expression of autophagy-related proteins Beclin-1 and BNIP3 and ischemic cardiomyopathy after adjusting for other confounding factors so as to provide reference for the mechanism of ICM and forensic research of ischemic cardiomyopathy.Methods: 1.Participants in ICM group(n=80)were selected from autopsy cases accepted by Forensic Judicial Expertise Center of Guizhou Medical University from July 2013 to December 2016,pathologically confirmed to have suffered “ischemic cardiomyopathy”.And participants in NICM group(n=122),the ones who without myocardial tissue lesions,were selected from autopsy cases accepted during the same period.Clinical data of subjects were collected.And baseline characteristics analysis and univariate analysis were performed on the collected clinical data.2.Samples of paraffin-embedded myocardial tissue were collected.And the expression levels of Beclin-1 and BNIP3 protein were detected in all samples by immunohistochemistry.The independent effect of Beclin-1 expression on ischemic cardiomyopathy was evaluated by establishing multiple Generalized Additive Models(GAM),adjusting the confounding factors such as gender,age,height,body mass index(BMI),left ventricular wall thickness(LVWT),right ventricular wall thickness(RVWT),alcohol abuse,Gensini score,previous myocardial infarction history(MI),hypertension,chronic kidney disease(CKD),and chronic respiratory disease.Stratified analysis and interaction test for the correlation between BNIP3 and ischemic cardiomyopathy were performed by three groups of regression models(Crude,model I,model II)were run for BNIP3,adjusting Beclin-1 as an effect modifier.Results: This researchdemonstrated that: 1.Gensini score(OR = 1.1;95% CI: 1.0-1.2;P <0.001),history of myocardial infarction(OR = 1.5;95% CI: 1.2-1.8;P <0.001),left ventricular wall thickness(OR=1.2;95% CI: 1.0-1.5;P=0.048)and right ventricular wall thickness(OR=1.1;95% CI:1.0-1.3;P=0.041)were positively correlated with ischemic cardiomyopathy.2.The expression of BNIP3 in cardiomyocytes was negatively correlated with ischemic cardiomyopathy(OR=0.8;95%CI: 0.6,1.0;P=0.016).The Expression of Beclin-1 in cardiomyocytes and was positively correlated with ischemic cardiomyopathy(OR=1.20;95%CI: 1.1-1.3,P<0.001).The trends of BINP3 and ICM are completely different in different Beclin-1 strata,which demonstrates that Beclin-1is a mediator of BINP3.Conclusion: 1.Gensini score,history of myocardial infarction,left ventricular wall thickness and right ventricular wall thickness are risk factors for ischemic cardiomyopathy.2.BNIP3 is an independent protective factor for ischemic cardiomyopathy.And Beclin-1 is an independent risk factor for ischemic cardiomyopathy.The effect of BNIP3 on ischemic cardiomyopathy is affected by Beclin-1.