Abstract

It has recently emerged that the mitochondria can play an important role in the control of vascular smooth muscle (VSM) cell proliferation. The mechanisms responsible for this control are largely unknown at least in part due to the limited size of the mitochondrial DNA. Recently a small number of miRNA have been reported to be present within the mitochondrial matrix.1. These studies suggest that mitochondrial miRNA or nuclear miRNA which regulate mitochondrial function could be responsible for the mitochondrial mediated control of VSM Cell proliferation.2 Indeed several miRNAs have been found to play an important role in switching VSM cells from a contractile to a synthetic phenotype including miR-145. Moreover, miR-378 has been associated with the activation of VSM cell pro-mitogenic signalling pathways.3 MiR-761 has been reported to regulate a number of mitochondrial functions including fission.4 Thus the aim of the current study was to investigate the potential role of mitochondria in regulating miRNA expression and possible influences on VSM cell proliferation.

MDivi-1 a DRP-1 inhibitor blocking mitochondrial fission attenuated VSM Cell proliferation in response to PDGF (p<0.05). Furthermore, addition of MDivi-1 resulted in a concentration dependent cell cycle arrest at G2/M phase (p<0.05). MiRNA profiling experiments reveal a role for miR-21 and miR-145 in these processes, since miR-21 was up-regulated and miR-145 is down-regulated following stimulation with PDGF. In concordance with the effects of SMC proliferation, treatment with MDivi-1 attenuated the up-regulation of miR-21 and down regulation of miR-145.

These data highlight the potential important role of mitochondria in vascular smooth muscle cell proliferation and highlight a link between miRNA expression, mitochondrial function and VSM cell proliferation.