The co-inertia approach in identification of specific microRNA in early and advanced atherosclerosis plaque

MicroRNAs (miRs) are short, non-coding RNAs that regulate gene expression by absolute or partial binding to mRNA, which results in transcript degradation and translation blocking. Atherosclerosis, as a complex and progressive disease, represents one of the main causes of cardiovascular clinical complications and even death. We applied co-inertia analysis (CIA) as a novel computation method, to determine which miRs are potentially associated with differences in gene expression levels originating from microarray data of early and advanced atherosclerotic plaque. As the CIA has not been applied in the field of atherosclerosis yet, we hypothesized that using CIA we can get novel information about the miRs that have significant role in early phase of disease or in severe phase of disease. The characteristic split in the data along the axes of performed CIA showed the difference in the gene expression pattern between early atherosclerosis and advanced atherosclerotic plaque. The advanced atherosclerotic plaques showed more homogenous gene expression pattern than early atherosclerosis samples. In early carotid lesions five out of five algorithms predicted miR-24, four out of five predicted miR-155, miR-145, and miR-100 as early active miRs. These miRs could be “protective” in plaque evolution context because they were not active in advanced plaques according to our results. They were reported previously as atheroprotective, which in a way represents confirmation of CIA application in atherosclerosis. We detected 13 new miRs which could be active in early plaque phenotype according to CIA prediction. In the advanced plaques we predicted miR-221, miR-222, miR-127 and miR-146 which were previously revealed to have atherogenic properties. In addition to miRs that have literature support, we also found new 8 miRs that, with described function so far, could present a novelty in research of atherosclerotic plaque evolution. All of these examples show that CIA results have a great potential to be of interest in future research in atherosclerotic plaque progression. We validated the applicability of CIA in the field of atherosclerosis, but we also found new interesting miR competitors that have strong potential to serve as markers and plaque development factors. These results should be experimentally confirmed in further research with ultimate goal to discover new mediators and blood markers, which could improve the prevention and therapy of this complex disease.