| First Author | Gupta SK | Year | 2016 |
| Journal | Cardiovasc Res | Volume | 110 |
| Issue | 2 | Pages | 215-26 |
| PubMed ID | 26865549 | Mgi Jnum | J:252639 |
| Mgi Id | MGI:6107288 | Doi | 10.1093/cvr/cvw030 |
| Citation | Gupta SK, et al. (2016) miR-21 promotes fibrosis in an acute cardiac allograft transplantation model. Cardiovasc Res 110(2):215-26 |
| abstractText | AIMS: Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood. METHODS AND RESULTS: To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR-21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts. CONCLUSION: Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts. |
