Moon Kamelia Zaman, Rahman Md Habibur, Alam Md Jahangir, Hossain Md Arju, Hwang Sungho, Kang Sojin, Moon Seungjoon, Park Moon Nyeo, Ahn Chi-Hoon, Kim Bonglee
Department of Computer Science and Engineering, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
Department of Computer Science and Engineering, Islamic University, Kushita 7003, Bangladesh.
Comput Biol Chem. 2025 Apr;115:108338. doi: 10.1016/j.compbiolchem.2024.108338. Epub 2024 Dec 30.
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-mir-23a-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.
临床观察表明，患有酒精使用障碍（AUD）的个体心血管疾病（CVD）明显加重，这表明这两种疾病之间存在复杂的相互作用。事实证明，找出这两种疾病的共同风险因素并非易事。为了解决这个问题，我们开创了一个复杂的生物信息学框架和基于网络的策略，以挖掘在AUD和CVD中表现出异常表达模式的基因。在同时患有AUD和CVD的患者的心脏组织样本中，我们的研究确定了76个差异表达基因（DEG），这些基因进一步用于检索重要的基因本体（GO）关键词和代谢途径，突出了促炎级联反应、T细胞细胞毒性、抗原加工和呈递等机制。通过蛋白质-蛋白质相互作用（PPI）分析，我们能够识别对这些疾病的病理生理学有重大影响的关键枢纽蛋白。确定的几个枢纽蛋白包括PTGS2、VCAM1、CCL2、CXCL8、IL7R，其中只有CDH1在cytoHubba插件的10种算法中被涵盖。此外，我们确定了几个转录因子（TF），包括SOD2、CXCL8、THBS2、GREM1、CCL2和PTGS2，以及潜在的微小RNA（miRNA），如hsa-mir-203a-3p、hsa-mir-23a-3p、hsa-mir-98-5p和hsa-mir-7-5p，它们对基因表达发挥着关键的调控作用……体外研究调查了酒精对HepG2和Hep3B细胞中E-钙黏蛋白（CDH1）表达 的影响，结果显示乙醇处理后表达显著下降。这些发现表明，酒精暴露可能会破坏细胞黏附，这可能导致与心血管疾病相关的细胞变化。我们的创新方法揭示了独特的生物标志物，描绘了AUD与各种心血管疾病之间的动态相互作用，以供未来进行治疗探索。
