The involvement of genes and miRNAs in the development of atherosclerosis is a challenging problem discussed in recent publications. It is necessary to establish which miRNAs affect the expression of candidate genes. We used known candidate atherosclerosis genes to predict associations. The quantitative characteristics of interactions of miRNAs with mRNA candidate genes were determined using the program, which identifies the localization of miRNA binding sites in mRNA, the free energy interaction of miRNA with mRNA. In mRNAs of GAS6 and NFE2L2 candidate genes, binding sites of 21 miRNAs and of 15 miRNAs, respectively, were identified. In IRS2 mRNA binding sites of 25 miRNAs were located in a cluster of 41 nt. In ADRB3, CD36, FASLG, FLT1, PLA2G7 , and PPARGC1A mRNAs, clusters of miR-466, ID00436.3p-miR, and ID01030.3p-miR BS were identified. The organization of overlapping miRNA binding sites in clusters led to their compaction and caused competition among the miRNAs. The binding of 53 miRNAs to the mRNAs of 14 candidate genes with free energy interactions greater than −130 kJ/mole was determined. The miR-619-5p was fully complementary to ADAM17 and CD36 mRNAs, ID01593.5p-miR to ANGPTL4 mRNA, ID01935.5p-miR to NFE2L2 , and miR-5096 to IL18 mRNA. Associations of miRNAs and candidate atherosclerosis genes are proposed for the early diagnosis of this disease.

No abstract

Ischemic heart disease (IHD) is the most serious cardiovascular disease and one of the leading causes of death worldwide. An important role in the pathophysiology of IHD play such processes as the processes of inflammation and immune response, metabolism of homocysteine and folate, development processes of endothelial dysfunction and oxidative stress and homeostasis system. Accordingly, the identified genes that are directly involved in these processes. In addition, miRNA (mRNA-inhibiting RNA) may affect the expression of these candidate genes. Using bioinformatics methods, the most efficient associations of miRNA and target genes were established. This research presents the characteristics of miRNA interactions with mRNA of candidate IHD genes. Candidate genes were identified that had a free energy of interaction with miRNA equal to -120 kJ / mole and higher in the following interactions: in 5’UTR - ALDH2 and ID02142.3p-miR; CELSR2 and ID00457.3p-miR; DDAH2 and ID01272.3p-miR; DNMT1 and ID02052.5p-miR; DOCK7 and ID00061.3p-miR; EGFR and ID02457.3p-miR; FOLH1 and ID01428.3p-miR; IL6R and miR-6089; NOS3 and ID02363.5p-miR; NPC1 and ID00551.3p-miR; PPP1R17 and ID01693.5p-miR; PRKCH and ID00520.5p-miR; SERPINE1 and ID01098.3p-miR; in CDS - ABCG8 and ID03064.3p-miR; ADORA2A and ID02697.3p-miR; APOA1 and ID00457.3p-miR; CDKN2B and ID02899.3p-miR; IL6R and ID01806.3p-miR; TIMP2 and ID00098.5p-miR; TNF and ID02050.3p-miR; TRIB1 and ID03208.5p-miR; VWF and ID01238.5p-miR. Associations were also revealed in the 3'UTR region with an interaction free energy of -115 kJ/mole and higher: AGTR2 and ID01213.5p-miR; APLNR and ID00616.5p-miR; CXCL12 and ID00483.3p-miR; FADS2 and miR-1224-3p; FCGR2A and miR-1273g-3p; GCKR and ID02928.3p-miR; IL6R and ID00913.5p-miR; KCNJ11 and ID03288.5p-miR; PPP1R3B and ID00913.5p-miR; TFPI and miR-1273g-3p; TIMP2 and ID01941.5p-miR. The results obtained could be used as molecular genetic markers of IHD for the diagnosis of this disease.

News of the National Academy of Sciences of the Republic of Kazakhstan. Series of biology and medicine.

Cardiovascular diseases, in particular myocardial infarction, are one of the most common causes of death in the world. To date, the risk assessment strategy infarction and post-infarction complications represent a significant problem sensitivity and predictive value of modern methods and markers, so the identification of new genetic markers is an actual problem. In this research, functionally significant candidate genes were studied, which are involved in the processes associated with the pathogenesis of myocardial infarction, in lipid metabolism, thrombus formation, endothelial dysfunction, and inflammatory reactions. However, in addition to genes, it has been determined that miRNA is also involved in the development of myocardial infarction by regulating the expression of target genes. This paper presents characteristics of miRNA interactions with mRNAs of candidate myocardial infarction genes. We have identified 34, 51 and 36 target genes that have miRNA binding sites in the 5'UTR, CDS, and 3'UTR regions, respectively. Based on the criteria chosen in our study, candidate genes were identified that have a free energy of interaction with miRNA equal to -120 kJ/mole and higher in the following associations: in 5’UTR - ID02142.3p-miR and ALDH2; ID00909.3p-miR and ALOX5; ID00216.3p-miR and CD40; ID01272.3p-miR and DDAH2; ID01774.5p-miR and IL6R; miR-6752-5p and KLF4; ID03332.3p-miR and LAMA3; ID02363.5p-miR and NOS3; ID02800.3p-miR and OPA1; ID01310.3p-miR and PDE4D; ID03397.3p-miR and PTGS2; ID01098.3p-miR and SERPINE1; ID01018.3p-miR and SGPP1; ID02430.3p-miR and SHH; ID01652.3p-miR and THBS1; ID01770.3p-miR and ZNF202; in CDS - ID00457.3p-miR and APOA1; ID00425.5p-miR and BTN2A1; ID01632.5p- miR and CCL5; ID02899.3p-miR and CDKN2B; miR-6894-5p and CYP1A2; ID01806.3p-miR and IL6R; ID01403.5p-miR and PLAUR; ID02950.3p-miR and SEMA3F; ID03332.3p-miR and SGPP1; ID02062.3p-miR and SIRT6; ID02050.3p-miR and TNF; ID01804.3p-miR and XBP1; ID00182.5p-miR and ZNF202; in 3’UTR - ID01293.5p-miR and SMTN; ID01882.5p-miR and TNNI3. The identified associations can be used as genetic markers in the diagnosis of myocardial infarction.