Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for EstablishingCaenorhabditis elegansas an Animal Model for Cardiovascular Diseases

Abstract

Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients andin vitroconditions. Animal models play a pivotal and indispensable role in cardiovascular disease (CVD) research.Caenorhabditis elegans, a nematode species, has emerged as a prominent experimental organism widely utilised in various biomedical research fields. However, the specific number of CVD-related genes and pathways within theC. elegansgenome remains undisclosed to date, limiting its in-depth utilisation for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans andC. elegansthrough a systematic bioinformatic approach.A total of 1113 genes inC. elegansorthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes inC. elegans, aPPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs:pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2,andaha-1 in C. elegans.Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans andC. eleganslinked with CVDs that include autophagy (animal), the ErbB signalling pathway, the FoxO signalling pathway, the MAPK signalling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present inC. elegans,supporting the use ofC. elegansas a prominent animal model organism for cardiovascular diseases.