Abstract 9685: Microrna-126-Containing Endothelial Microparticles Reduce Neointimaformation and Vascular Smooth Muscle Cell Proliferation
Itroduction: Endothelial microparticles (EMP) have been shown to promote vascular regeneration by transferring functional microRNAs, but whether they influence VSMC biology is largely unknown.
Hypothesis: EMP influence neointima formation in a model of acute vascular injury in vivo and VSMC proliferation and migration in vitro.
Methods and Results: After wire injury of the carotid artery, mice treated with EMP showed a significantly reduced neointima formation (0.63±0.03 vs. 0.47±0.04,p<0.05, n=8). Furthermore, VSMCs treated with EMP displayed significantly reduced proliferation and migration capacities in vitro, both critical steps in neointima formation. In order to dissect the underlying mechanisms of EMP-promoted inhibition of VSMC proliferation and neointima formation, 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. Interestingly, expression of miR-126 target protein LRP6, regulating VSMC proliferation, was reduced in VSMCs after EMP treatment. Genetic knockdown of miR-126 in EMP abrogated EMP-mediated inhibition of LRP6 expression and subsequently VSMC migration and proliferation in vitro and neointimaformation in vivo, suggesting a crucial role of miR-126 in EMP-mediated neointima formation reduction. Finally, expression analysis of miR-126 in circulating MPs in 176 patients with CAD revealed that patients with high level of miR-126 within circulating MPs have a significantly reduced MACE- and revascularization rate in a 6-year follow up period, supporting a central role for miR-126 in MPs in the regulation of vascular health.
Conclusions: EMP reduce neointima 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 mir-126 by EMP and subsequent inhibition of LRP6 expression in VSMCs might be a possible pathway.
Author Disclosures: F. Jansen: None. T. Stumpf: None. G. Nickenig: None. N. Werner: None.
- © 2014 by American Heart Association, Inc.