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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 - Zurich Open Repository and Archive


Jakob, Philipp; Doerries, Carola; Briand, Sylvie; Mocharla, Pavani; Kränkel, Nicolle; Besler, Christian; Mueller, Maja; Manes, Costantina; Templin, Christian; Baltes, Christof; Rudin, Markus; Adams, Heiner; Wolfrum, Mathias; Noll, Georg; Ruschitzka, Frank; Lüscher, Thomas; Landmesser, Ulf (2012). 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. Circulation, 126(25):2962-2975.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:14 Dec 2012 16:02
Last Modified:05 Apr 2016 16:11
Publisher:American Heart Association
ISSN:0009-7322
Publisher DOI:https://doi.org/10.1161/CIRCULATIONAHA.112.093906
PubMed ID:23136161

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