The Communal Pathogenesis, Autophagy Mechanism and Potential Therapeutic Targets in Dilated Cardiomyopathy and Viral Myocarditis

Abstract

Abstract Background: Viral myocarditis (VMC) is an important factor leading to dilated cardiomyopathy (DCM), yet the molecular mechanism is far from elucidated. Autophagy has been proven to be associated with cardiomyopathies, but the role of autophagy in the progression from VMC to DCM is unclear and requires further study. Methods: Common differentially expressed genes (CoDEGs) in DCM and VMC were screened from the related microarray datasets. Enrichment analysis and protein-protein interaction analysis were performed to identify key pathways and Hub Genes. The differentially expressed ARGs were used for receiver operating characteristic analysis to identify potential biomarkers. The expression of these identified genes was further verified in external datasets. Results: A total of 134 CoDEGs were identified and these genes were mainly enriched in the pathways of “inflammatory response”, “response to virus”, “JAK-STAT signaling pathway”, and “PI3K-Akt signaling pathway”. The top 6 hub genes CCND1, STAT3, THBS1, CCL2, POSTN, IFIT2 and 11 Common differentially expressed ARGs BCL2L1, CCL2, CCND1, NAMPT, NRG1, S100A8, S100A9, SESN3, SNCA, STAT3, TUBA1C were identified. These genes had a similar expression pattern in DCM and VMC. Finally, in the external validation dataset, mice showed an enhanced inflammatory response and apoptotic response at the initial stage of coxsackievirus B3 infection and indicated DCM phenotype in the chronic stage of infection. Conclusions: Inflammatory response and autophagy may be the vital biological pathways in the progression from VMC to DCM, and appropriate intervention of these processes may be a novel and potential therapeutic strategy.