The Pathogenetic Significance of miR-143 in Atherosclerosis Development

Our pilot studies of blood plasma in patients with comorbidities allow miR-143 to be regarded as a potential biomarker of atherosclerosis expression, but the literature data on the dynamics of miR-143 expression are too controversial. The continuation of the study to verify the results by “wet lab” methods is costly and therefore it is advisable to first determine whether the putative biomarker has pathogenic relevance. The aim of the study was to establish and assess the role of miR-143 in atherosclerosis using a comprehensive bioinformatics analysis, to identify possible pathways of its inclusion in the pathology mechanism. Using open sources, two sets of gene expression data in atherosclerotic plaques were selected, then only differentially expressed genes (DEGs) shared by both datasets were identified, from which a protein-protein interaction (PPI) extended network was then constructed. The next step was network analysis (identification of clusters and hub genes within them) and construction of regulatory networks of miRNAs-hub genes. The analysis revealed that miR-143 is one of the central miRNAs whose action may be associated with suppression of atherosclerosis formation through its targeting of several hub genes: TLR2, TNF and LYN. However, another target is ITGB1, whose reduction increases autophagy and activates the inflammatory response. Based on established topological and functional characteristics, miR-143 is of interest for further verification as a biomarker and for possible therapeutic applications in atherosclerosis. We also cut through the perspective of the already known effects of miR-143 on the NK-kB pathway, but in the context of atherosclerosis (via TNF and TLR2).