Shared Genetic Characteristics of Coronary Artery Disease and Peripheral artery Disease: Insights From Integrated Bioinformatics Analysis of RNA-Sequencing Data.

Abstract

Coronary artery disease (CAD) and peripheral artery disease have serious effects on quality of life. Recent studies have shown that peripheral arterial disorders increase a person's risk of developing CAD. The clinical symptoms of these conditions include palpitations, fatigue, confusion, shortness of breath, and, in severe cases, heart failure or stroke. Despite these similarities, many diseases have no known treatments, which raises grave concerns for world health. The study aims to identify common differentially expressed genes (DEGs) between CAD and peripheral arterial disease (PAD) patients and investigate biological pathways, network-based analysis, immune and inflammatory profiling, biomarker identification, and multi-omics integration. This helps in early detection and targeted treatment strategies. The results revealed 48 upregulated DEGs that were shared among CAD and peripheral arterial disorders. Functional enrichment analysis revealed mainly myofibril assembly and actomyosin organization, highlighting muscle development and cellular structure, and KEGG pathway analysis revealed amino acid metabolism pathways. A network of protein-protein interactions (PPIs) was built via the STRING and visualized by Cytoscape plugin, CytoHubba, and MCODE, which led to the identification of 10 hub genes, ie, GLS, CCND2, RBL2, ITGB1, IL6ST, THRB, MBNL1, PDE5A, PROS1, and CACNA2D3. Most of these genes involved in key functions, such as voltage-gated calcium channel trafficking, cGMP degradation, RNA splicing, thyroid hormone receptor beta, IL6ST, and cytokine signaling, play crucial roles. Within this subnetwork, we identified 10 crucial seed nodes that are integral to the network's structure and function. The seed nodes highlight significant regulatory connections, providing insights into the underlying biological mechanisms involved. The transcription factor regulatory network of the hub genes revealed this phenomenon. Finding the important seed nodes in this regulatory network makes their role in maintaining the network's integrity and functionality even more clear. This could lead to new targeted therapies and better ways of managing CAD and peripheral blood disorders.