Table 2.

Other miRNAs associated with cardiac allografts rejection and function

miRNA	Description	Ref.
miR-146a	Model: BALB/c to C57BL/6J (B6) C57BL/6J recipients were injected with miR-146a antagomir prior allograft transplantation. miR-146a antagomir increased the Treg proportion in splenocytes and blood cells, which promoted the survival of the donor's heart.	72
miR-449	Model: BALB/c to C57BL/6 miR-449a expression increase in PBMCs and GILs during allograft rejection and CD4+ T-cell activation. Inhibition of miR-449a caused alteration in metabolic potential (glycolysis and maximum glycolytic capacity decreased after miR-499 inhibition), decrease in mitochondrial respiration, and thus seems to be involved in regulating energetic metabolism of CD4+ T-cells.	73
miR-669b-3p	Model: C57BL/6 to BALB/c After initial miRNA profiling and identification of 93 up-regulated and 78 downregulated miRNAs, miR-669b-3p upregulation was confirmed by qPCR and was further studied using cell cultures. Indoleamine-2,3-dioxygenase (IDO) was determined in silico as a mechanistic target and using mouse 3 T3 cell lines overexpressing or knock-out in miR-669b-3p, levels of IDO were shown to be decreased or increased, respectively. Increased levels of IDO then inhibited CD4+ T cell proliferation and promoted apoptosis.	74
miR-774	Model: C57BL/6 to BALB/c Expression of miR-744 in CD4+CD25+Treg cells from CAT mice was significantly lower. Use of agomir for miR-744 increased levels of miR-744 in CD4+CD25+Treg cells in the CAT group but not in the control group. TNFRSF4 gene was identified as the miR-744 mechanistic target. Functionally, the inhibitory function of Treg cells was significantly enhanced in miR-744 agomir treated mice, and this resulted in prolonged survival time of cardiac allograft.	57
miR-377	Model: Neonatal rat (0-3 d) primary cardiomyocytes Cyclosporine A (CsA) increased apoptosis of neonatal rat cardiomyocytes. Using microarray assay, 17 miRNAs were shown to be altered in CsA treated groups, out of which miR-377 was the most significantly increased. Transfection of miR-377 increased cardiomyocytes apoptosis and vice versa; anti-miR-377 decreased cardiomyocytes apoptosis even after the CsA treatment. XIAP and NRP2 were identified as miR-377 mechanistic targets.	75
miR-223	Model: C57BL/10 (H2-Kb) to CBA/N (H2-Kk) Transplanted animals were administered with eicosapentaenoic acid (EPA), which significantly prolonged the survival of cardiac allografts. Authors focused on the groups of 10 miRNAs previously reported by their group to be altered in hepatic allografts and confirmed that levels of miR-223 were increased in the rejection group while the levels of other miRNAs (mir-146a, -15b, -23a, -34a, -451, -101a, -101b, and -148a) were increased in animals treated with EPA, suggesting the role of miR-223 in allograft rejection and the role for the rest of miRNAs in the allograft tolerance.	76