Key result
Genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in murine cardiac allografts.
Why the study?
Does genetic or pharmacological inhibition of miR-21 reduce fibrosis in cardiac allografts?
Does genetic or pharmacological inhibition of miR-21 reduce fibrosis in cardiac allografts?
Inhibition of miR-21 represents a potential novel therapeutic strategy to prevent fibrosis and improve outcomes in cardiac allografts.
miR-21 inhibition attenuates fibrosis in murine allografts; leaves open translation to human cardiac transplant recipients.
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.
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Gupta et al. (2016) studied Cardiac allograft transplantation and fibrosis. miR-21 inhibition (genetic and pharmacological) vs. Control/isografts was evaluated on Fibrosis and fibrocyte accumulation in cardiac allografts. Genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in murine cardiac allografts.
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