Cross-disease Study Of Ischemic Heart Disease And Diabetic Cardiomyopathy Illness-related Genes And Significance

Objective and Background:Ischemic heart disease(IHD)and diabetic cardiomyopathy(DCM)are common causes of death in diabetic patients,and their pathogenesis has a certain commonality;the two also have common features in pathology,both of which show changes in coronary circulation and myocardial cell causes Ischemia and hypoxia cause apoptosis,necrosis and loss,and eventually lead to sudden death or heart failure.Therefore,they are quite difficult to identify in forensic pathology.Further discussion of IHD,DCM and diabetes complicated with IHD and DCM gene changes and the mechanism of related potential genes has important theoretical research value and the significance of forensic pathology identification.Relevant research shows that the gene expression is different in different stages of the development of diabetes complicated with heart disease.They participate in the pathological process of diabetes complicated with IHD and DCM,and some may be used as potential targets for diagnosis and treatment of multiple diseases.Systems biology analysis provides strategies for exploring the causative mechanism of specific causal diseases.Therefore,this study used bioinformatics methods to explore the possible pathogenesis of diabetes complicated by IHD and DCM across diseases,to further obtain information about its closely related and shared differentially expressed genes and to participate in biological processes,and to culture myocardial cells by simulating a diabetic environment in vitro,To observe the key gene expression of H9c2 cardiomyocytes during hypoxia,and to explore its significance in the identification of diabetes with IHD and DCM forensic pathology.Materials and Methods:1.Download the m RNA expression chips of IHD and DCM through the GEO database,including two independent datasets GSE79962 and GSE26887.2.Use the GEO2 R online analysis tool to screen the original gene expression data between the IHD group,the DCM group and the control group.3.Use the limma package to screen for differentially expressed genes(DEGs),and then use the Metascape database online tool to perform functional enrichment analysis on DEGs,observe their biological processes and KEGG Pathway enrichment,and then select the IHD through the direction of gene fold change.DEGs that are closely related to DCM.4.By simulating the diabetic environment in vitro,SD rat H9c2 cardiomyocytes were selected,then through the cck-8 cardiomyocyte cytotoxicity experiment to explore the effect of glycolipid toxicity on cell viability of H9c2 cardiomyocytes in different time periods,and finally divided into normal group and high In the sugar group,high glucose and high fat group,and high glucose and high fat hypoxia group,H9c2 cardiomyocytes were treated for 24 hours and then collected from each group of cells for Western Blot experiments to further verify the key genes involved in the biological process of enriching DEGs.Result:1.Screen the DEGs of the two data sets with gene fold change(FC)? 2,and p<0.05.In GSE79962,compared with the control group,127 DEGs were obtained,of which 46 genes were up-regulated and 81 genes were expressed Down regulation;in GSE26887,compared with the control group,230 DEGs were found,of which 131 genes were up-regulated and 99 genes were down-regulated.Then compare the DEGs of the two data sets by Venn diagram(venn),and get 46 overlapping DEGs.2.The analysis of the biological process(BP)enrichment of DEGs showed that the DEGs of IDH mainly involved positive regulation of cell-matrix adhesion and positive regulation of inflammatory response.The DEGs of DCM mainly involve extracellular structure and tissues,and negative regulation of smooth muscle cell proliferation.The DEGs overlapped by IHD/DCM mainly involve extracellular structure and tissues,acute inflammatory response,etc.3.The KEGG Pathway enrichment analysis results of DEGs show that IHD DEGs mainly involve osteoclast differentiation signaling pathway and PPAR signaling pathway.DCM's DEGs mainly involve drug metabolism-cytochrome P450 signaling pathway,Toll-like receptor signaling pathway,etc.DEGs overlapped by IHD/DCM are mainly involved in the complement and coagulation cascade signaling pathways.4.Screen the shared DEGs through the direction of fold change and find that compared with the control group,the expression levels of HMGCS2 and ADH1 B increased significantly in diabetes complicated with IHD and DCM,while the expression level of OTUD1 decreased.5.In vitro experiments,H9c2 cardiomyocytes were treated with high-glucose DMEM medium containing various concentrations of palmitic acid(PA)for 24 h and 48 h,respectively,and it was found that the concentration of PA(200?800 ?M)promoted cell death in a dose-dependent manner And the cell viability of PA at 400 u M is about 50% of that at 0u M.Finally,Western blot experiments were used to further explore the normal group,high glucose group,high glucose and high fat group,and high glucose and high fat group combined with hypoxia treatment of H9c2 cardiomyocytes for 24 h.The results showed that high glucose and high fat and higher glucose promoted cardiomyocyte apoptosis markers The expression of Bax and high glucose and high fat hypoxia are more likely to promote the expression of MMP9,a marker of fibrosis in H9c2 cardiomyocytes.Conclusion:1.The expression levels of HMGCS2 and ADH1 B are significantly increased in the myocardium of patients with diabetes complicated with IHD and DCM,while the expression levels of OTUD1 are significantly reduced,suggesting that these three genes are closely related to the occurrence and development of diabetes complicated with IHD and DCM,and may be used as potential Diagnosis,forensic pathology identification biomarkers and clinical treatment targets.2.In a high glucose environment,palmitic acid significantly reduces cell viability in a dose-dependent manner,which may be related to glycolipid toxicity promoting H9c2 cardiomyocyte apoptosis.3.High glucose and high fat combined with hypoxia promotes fibrosis of H9c2 cardiomyocytes,which can be used as a potential molecular mechanism to supplement the rational remodeling of heart disease caused by diabetes complicated with IHD.