Loss of AngiomiR-126 and 130a in Angiogenic Early Outgrowth Cells From Patients With Chronic Heart Failure
| Autor: | Ulf Landmesser, Thomas F. Lüscher, Frank Ruschitzka, Maja Mueller, Mathias Wolfrum, Sylvie Briand, Christian Besler, Heiner Adams, Costantina Manes, Markus Rudin, Philipp Jakob, Nicolle Kränkel, Carola Doerries, Christian Templin, Pavani Mocharla, Georg Noll, Christof Baltes |
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| Přispěvatelé: | University of Zurich, Landmesser, Ulf |
| Rok vydání: | 2012 |
| Předmět: |
Male
Cardiac function curve Myeloid endocrine system diseases Angiogenesis Myocardial Ischemia Neovascularization Physiologic Antigens CD34 610 Medicine & health 030204 cardiovascular system & hematology 2705 Cardiology and Cardiovascular Medicine Neovascularization Mice 03 medical and health sciences 2737 Physiology (medical) 0302 clinical medicine Physiology (medical) medicine Animals Humans Myocardial infarction Adaptor Proteins Signal Transducing 030304 developmental biology Heart Failure Homeodomain Proteins 0303 health sciences Ischemic cardiomyopathy business.industry Intracellular Signaling Peptides and Proteins Membrane Proteins Heart Middle Aged medicine.disease female genital diseases and pregnancy complications Transplantation MicroRNAs medicine.anatomical_structure 10076 Center for Integrative Human Physiology Heart failure Chronic Disease Immunology cardiovascular system 10209 Clinic for Cardiology Cancer research 570 Life sciences biology Female medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.112.093906 |
| Popis: | 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 caused by ischemic cardiomyopathy (n=45) and healthy subjects (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. Cardiac transplantation of angiogenic EOCs from healthy subjects markedly increased neovascularization and improved cardiac function, whereas no such effect was observed after transplantation of angiogenic EOCs from patients with CHF. Real-time polymerase chain reaction 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 healthy subjects 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. |
| Databáze: | OpenAIRE |
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