Endothelial Microparticle-Mediated Transfer of MicroRNA-126 Promotes Vascular Endothelial Cell Repair via SPRED1 and is Abrogated in Glucose-Damaged Endothelial Microparticles
Background—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. We sought to investigate whether endothelial microparticles (EMP), released from apoptotic endothelial cells (ECs), influence EC repair.
Methods and Results—Systemic treatment of mice with EMP after electrical denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes 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. Following experiments demonstrated that miR-126 was transported into recipient HCAEC by EMP and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMP abrogated EMP-mediated effects on HCAEC migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMP derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients.
Conclusions—Endothelial microparticles promote vascular endothelial repair by delivering functional microRNA-126 into recipient cells. In pathological hyperglycaemic conditions, EMP-mediated miR-126-induced EC repair is altered.
- Received February 5, 2013.
- Revision received August 12, 2013.
- Accepted August 22, 2013.