Abstract 10882: Endothelial Microparticle-mediated Transfer of MicroRNA-126 Promotes Vascular Endothelial Cell Repair Via SPRED1 and is Abrogated in Glucose-damaged Endothelial Microparticles
Introduction: Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. Here, we sought to investigate whether endothelial microparticles (EMP), released from apoptotic endothelial cells (ECs), influence EC repair.
Methods and Results: EMP were generated from human coronary endothelial cells (HCAEC). Systemic treatment of mice with EMP after electrical denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP promote EC migration and proliferation, both critical steps in endothelial repair. 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 (n=3). Following experiments demonstrated that miR-126 was transported into recipient HCAEC by EMP and functionally regulated the target protein SPRED1. Knockdown of miR-126 in EMP abrogated EMP-mediated effects on EC migration and proliferation in vitro and reendothelialization in vivo, confirming the crucial role of miR-126 in EMP-mediated endothelial regeneration. Next, we tested whether EMP generated under pathological hyperglycaemic conditions (defined as ,,injured" EMP, (iEMP)) differed in miR expression and function from EMP. Interestingly, Taqman microRNA-array analysis revelaed that miR-126 was the strongest regulated miR between iEMP and EMP (n=3). Subsequently, iEMP showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with and without diabetes revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients.
Conclusion: Endothelial microparticles promote vascular endothelial repair by delivering functional microRNA-126 into recipient cells. This leads to downregulation of target protein Spred1 and improves migratory and proliferative EC capacity with subsequent improvement of EC repair. In pathological hyperglycaemic conditions, EMP-mediated miR-126 induced EC repair is altered.
- © 2013 by American Heart Association, Inc.