Inhibition of miR-92a increases endothelial proliferation and migration in vitro as well as reduces neointimal proliferation in vivo after vascular injury

The role of miR-92a on vascular remodelling after injury is currently unknown. Thus, the aim of the present study was to evaluate the role of miR-92a on rat endothelial and vascular smooth muscle cells proliferation and migration in vitro as well as after balloon injury or arterial stenting in vivo. MiR-92a was highly expressed in RAO-ECs and vascular endothelium, but not in RAOSMCs or medial smooth muscle as assessed by real-time RT-PCR. Importantly, BrdU incorporation and wound healing assay provide evidence that functional inhibition of miR-92a resulted in an increased RAO-ECs proliferation and migration, but had no effect on RAO-SMCs proliferation or migration in vitro. Immunoblotting analysis revealed an increased phosphorylation of ERK1/2, JNK/ SAPK as well as eNOS and phospho-eNOS increased expression level in RAO-ECs as a consequence of miR-92a inhibition. Using gain and loss of function experiments, we showed that miR-92a modulates regulation of KLF4 and MKK4 expression level in endothelial cells. Finally, in vivo administration of antagomiR-92a significantly enhanced re-endothelialization in injured carotid arteries and reduced neointimal formation after balloon injury or arterial stenting. These data provide the first evidence that inhibition of miR-92a may represent a novel strategy to improve endothelial regeneration and reduce restenosis after vascular injury. © Springer-Verlag 2012