MicroRNA-126-containing endothelial microparticles reduce neointimaformation and vascular smooth muscle cell proliferation

Abstract

Listen

Translate article

Background: Vascular Smooth Muscle Cell (VSMC) proliferation is of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Endothelial Microparticles (EMP) have been shown to promote vascular regenration by transferring functional microRNAs, but whether they influence VSMC biology is largely unknown. We explored the influence of EMP on neointima formation in a model of acute vascular injury in vivo and on VSMC proliferation and migration in vitro. Methods and results: After wire injury of the carotid artery, mice were treated systemically with EMP generated from Human Coronary Artery Endothelial Cells (HCAEC). Mice treated with EMP showed a significantly reduced neointimal formation (0.63±0.03 vs. 0.47±0.04,p<0.05, n=8). Furthermore, VSMCs treated with EMPs showed significantly reduced proliferation and migration capacities, both critical steps in neointimaformation (p<0.05 after 6h, p<0.01 after 8 h, n=7-8). Following experiments revealed a time dependent uptake of EMP into VSMCs in vitro. In order to dissect the underlying mechanisms, Taqman microRNA-array was performed and microRNA (miR)-126 was identified as the predominantly expressed miR in EMP. Furthermore, miR-126 was transported into recipient VSMC by EMP (1±0.05 vs. 1.34±0.05, p<0.05). Interestingly, expression of the target protein LRP6, regulating VSMC proliferation, was altered in VSMCs after EMP treatment. Conclusions: Endothelial microparticles reduce neointimal formation in a model of acute arterial injury in vivo and decrease proliferation and migration of vascular smooth muscle cells in vitro. The transfer of mir126 by EMP and subsequent regulation of LRP6 expression in VSMCs might be a possible pathway.