CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 310 AFRICA immediately after 10 minutes of application. However, verapamil has been demonstrated to have depressive effects on the AV node.23 Previous research suggested that AV block is commonly associated with therapy with verapamil but it is rarely caused by it.24 Our results indicated that AV blocks were associated with verapamil pretreatment, which is similar to previous research. We found that the anti-arrhythmic effects of VRP in this study are similar to the preliminary data from different studies using both streptomycin and gadolinium.25,26 According to the KEGG analysis of the DEGs, the enriched pathways included the pathways of adherens junctions and those involved in regulation of actin cytoskeleton and MAPK signalling. The actin cytoskeleton pathways play an important role in the morphology of cardiomyocytes and in the maintenance of membrane subdomains such as intercalated discs, caveolae and T-tubules. These pathways are also important in the trafficking of gap junction channels.27-30 The cardiomyocyte cytoskeleton integrates with the extracellular matrix and senses biomechanical stress.31 When met with mechanical overload stress, the cytoskeleton translates wall stress into alterations in cell stiffness and T-tubule structure, in both adaptive and maladaptive responses. The actin cytoskeleton may act as a regulator of cell morphology and alter Ca2+ Pathways in cancer MAPK-signalling pathway Regulation of actin cytoskeleton Focal adhesion Insulin-signalling pathway Neurotrophin-signalling pathway Axon guidance Adherens junction Renal cell carcinoma Dorsoventral axis formation KEGG pathway Rich factor 1 2 3 Count –Log10 p-value 10 20 30 40 6.5 6.0 5.5 5.0 4.5 Fig. 6. Top 10 signalling pathways enriched from candidate target genes using KEGG analysis. The rich factor is the ratio of the number of DEGs annotated in a given pathway term to the number of all genes annotated in the pathway term. A higher rich factor indicates greater intensity. The sizes of the circles indicate the number of genes. KEGG, Kyoto Encyclopedia annotation of Genes and Genomes. Fig. 7. Network analysis of DEGs. Nodes: the number of networking proteins; edges: interactions between protein(s) and protein(s). Red and blue nodes represent up- and downregulated genes, respectively; yellow nodes represent the hub genes. DEGs, differentially expressed genes; PPI, protein–protein interaction.
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