Loss of AngiomiR-126 and 130a in Angiogenic Early Outgrowth Cells from Patients with Chronic Heart Failure: Role for Impaired in vivo Neovascularization and Cardiac Repair Capacity
Background—MicroRNAs are key regulators of angiogenic processes. Administration of angiogenic early outgrowth cells (EOCs) or CD34+-cells has been suggested to improve cardiac function after ischemic injury in particular by promoting neovascularization. The present study therefore examines regulation of angiomiRs, microRNAs involved in angiogenesis, in angiogenic-EOCs and circulating CD34+-cells from patients with chronic heart failure (CHF) and the role for their cardiac repair capacity.
Methods and Results—Angiogenic-EOCs and CD34+-cells were isolated from patients with CHF due to ischemic cardiomyopathy (n=45) and healthy subjects (HS; n=35). In flow-cytometry analyses angiogenic-EOCs were largely myeloid and positive for alternatively-activated, M2-macrophage markers. In vivo cardiac neovascularization and functional repair capacity were examined after transplantation into nude mice with myocardial infarction (MI). Cardiac transplantation of angiogenic-EOCs from HS markedly increased neovascularization and improved cardiac function, whereas no such effect was observed after transplantation of angiogenic-EOCs from patients with CHF. RT-PCR analysis of 14 candidate angiomiRs, expressed in angiogenic-EOCs, revealed a pronounced loss of angiomiR-126 and -130a in angiogenic-EOCs from patients with CHF, that was also observed in circulating CD34+-cells. Anti-miR-126 transfection markedly impaired the capacity of angiogenic-EOCs from HS to improve cardiac function. miR-126-mimic transfection increased the capacity of angiogenic-EOCs from patients with CHF to improve cardiac neovascularization and function.
Conclusions—The present study reveals a loss of angiomiR-126 and -130a in angiogenic-EOCs and circulating CD34+-cells from patients with CHF. Reduced miR-126 expression was identified as a novel mechanism limiting their capacity to improve cardiac neovascularization and function that can be targeted by miR-126-mimic-transfection
- chronic heart failure
- endothelial progenitor cells
- ischemic cardiomyopathy
- angiogenic early outgrowth cells
- Received January 19, 2012.
- Accepted October 22, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited