Abstract 21339: Antimir Treatment Reveals a Critical Role of Mir-126 and Mir-130a for in vivo Cardiac and Endothelial Repair Capacity of Early Endothelial Progenitor Cells: Marked Down-Regulation in Patients With Ischemic Cardiomyopathy
Background: Early endothelial progenitor cells (EPCs) promote cardiovascular repair mechanisms. However, functional repair capacity of EPCs may be altered in cardiovascular disease, therefore representing an important potential limitation for autologous cell-based treatment approaches. We therefore characterised differential microRNA regulation in these cells from patients with ischemic cardiomyopathy (ICM) as compared to healthy subjects (HS) and characterised their role for in vivo cardiac and endothelial repair capacity of early EPCs.
Methods: Early EPCs were isolated from peripheral blood of patients with ICM and HS. The microRNA expression profile of early EPCs was characterised using a microRNA array. Differential microRNA expression was examined by quantitative RT-PCR. In vivo cardiac and endothelial repair capacity of EPCs were examined after transplantation into nude mice with myocardial infarction and carotid injury. The functional role of differentially regulated microRNAs was examined by transfection of early EPCs with antimirs.
Results: MicroRNA profiling indicated a markedly reduced expression of the miR126 and miR130a in EPCs from patients with ICM. Furthermore, levels of the respective targets, SRED-1 and HOXA-5, were up-regulated in these cells. In vivo cardiac and endothelial repair capacity of EPCs derived from patients with ICM was markedly reduced as compared to HS. Cardiac function improved after transplantation of EPCs from healthy subjects, but not after transplantation of EPCs from patients with ICM. Notably, down-regulation of miR126 and miR130a impaired the cardiac repair capacity of EPCs from HS, and down-regulation of miR130a, but not of miR126 abolished endothelial repair capacity of EPCs from HS.
Conclusions: Down-regulation of miR126 and miR130a impairs the pro-angiogenic effects of early EPCs, whereas down-regulation of miR130a abolishes the endothelial repair capacity of early EPCs in patients with ICM. Altered microRNA regulation likely represents an interesting target for the optimisation of cell-based treatment approaches in these patients, given a markedly impaired in vivo cardiac and endothelial repair capacity of early EPCs from patients with ICM.
- © 2010 by American Heart Association, Inc.