Mirnas as Potential Diagnostic Tool for Diabetes-Linked Myocardial Infarction

Abstract

Cardiovascular diseases affect millions of people worldwide with a prevalence of 17.9 deaths in 2019. Myocardial infarction (MI) is the initial indicator of heart failure associated with reduced blood flow causing cardiac cell apoptosis. Diabetic patients exhibit a 2-4 fold increase in risk in the development of cardiovascular disease, especially MI. Material and Methods We have used Gene Target Registry (GTR) and National Center for Biotechnology Infromation database to find dysregulated genes in diabetes-linked MI patients. Insilico analysis was done to find miRNAs targeting the dysregulated genes by using Targetscan, miRBase, and miRanda databases. MicroRNAs (miRNAs) were isolated from peripheral blood of diabetic MI patients'admitted in Lady Reading Hospital Peshawar, and western blot was used to assess its target protein expression – recipocal conformation of miRNA expression levels with its target protien inhibition. qRT-PCR and various biochemical assays were performed to explore the diagnostics potential of circulatory miRNAs including miR-15 in a diabetic MI patients’ blood. Results In this study, we identify many genes which have the 8-mers binding site of miRNA by using various bioinformatics tools. We find out that various genes including KCNQ1, CDKN2A, CDKN2B-AS1, and VEGF are dysregulated in diabetes-linked MI. KCNQ1 is a putative target of miRNA-365a and miRNA-365b. CDKN2A is another target of miR-484, miR-3155, miR-4466, miR-675, miR-6804, and miR-500. miR-15a is upregulated in diabetes linked MI patients, Vascular endothelial growth factor (VEGF) is the putative target of miRNA-15a. In addition, the bioinformatics analysis showed that VEGF has the target site for other miRNAs including miRNA-16, miRNA-195, miR-6838, miR-497, miR-424. Further expression analysis have confirmed miR-15a to be upregulated in diabetic MI patients’ blood. Conclusion Conclusively, these miRNAs may sever as a diagnostic marker for diabetes link MI. Furthermore, the circulatory miR-15a exhibits diagnostic potential for diabetes link MI and provide a therapeutic target for MI in diabetic patients.