Unraveling the interplay between cardiovascular diseases and alcohol use disorder: A bioinformatics and network-based exploration of shared molecular pathways and key biomarkers validation via western blot analysis

Clinical observations indicate a pronounced exacerbation of Cardiovascular Diseases (CVDs) in individuals grappling with Alcohol Use Disorder (AUD), suggesting an intricate interplay between these maladies. Pinpointing shared risk factors for both conditions has proven elusive. To address this, we pioneered a sophisticated bioinformatics framework and network-based strategy to unearth genes exhibiting aberrant expression patterns in both AUD and CVDs. In heart tissue samples from patients battling both AUD and CVDs, our study identified 76 Differentially Expressed Genes (DEGs) further used for retrieving important Gene Ontology (GO) keywords and metabolic pathways, highlighting mechanisms like proinflammatory cascades, T-cell cytotoxicity, antigen processing and presentation. By using Protein-Protein Interaction (PPI) analysis, we were able to identify key hub proteins that have a significant impact on the pathophysiology of these illnesses. Several hub proteins were identified include PTGS2, VCAM1, CCL2, CXCL8, IL7R, among these only CDH1 was covered in 10 algorithms of cytoHubba plugin. Furthermore, we pinpointed several Transcription Factors (TFs), including SOD2, CXCL8, THBS2, GREM1, CCL2, and PTGS2, alongside potential microRNAs (miRNAs) such as hsa-mir-203a-3p, hsa-mir23a-3p, hsa-mir-98-5p, and hsa-mir-7-5p, which exert critical regulatory control over gene expression... In vitro study investigates the effect of alcohol on E-cadherin (CDH1) expression in HepG2 and Hep3B cells, showing a significant decrease in expression following ethanol treatment. These findings suggest that alcohol exposure may disrupt cell adhesion, potentially contributing to cellular changes associated with cardiovascular diseases. Our innovative approach has unveiled distinctive biomarkers delineating the dynamic interplay between AUD and various cardiovascular conditions for future therapeutic exploration.