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
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
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DOI：
10.1161/circulationaha.112.093906
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发表时间：
2012-12-18
期刊：
影响因子：
37.8
通讯作者：
Landmesser, Ulf
中科院分区：
文献类型：
--
作者：
Jakob, Philipp;Doerries, Carola;Landmesser, Ulf
背景-MicroRNA是血管生成过程的关键调节因子。血管生成早期生长细胞（EOCs）或CD 34（+）细胞的管理已被建议改善缺血性损伤后的心脏功能，特别是通过促进新血管形成。因此，本研究检测了慢性心力衰竭（CHF）患者的血管生成EOCs和循环CD 34（+）细胞中血管生成miRs（参与血管生成的microRNA）的调节及其心脏修复能力的作用。方法和结果-从缺血性心肌病引起的CHF患者（n = 45）和健康受试者（n = 35）中分离出血管生成EOCs和CD 34（+）细胞。在流式细胞术分析中，血管生成性EOC主要是髓样的，并且对交替激活的M2巨噬细胞标志物呈阳性。移植到心肌梗死的裸鼠体内后，检测体内心脏新生血管和功能修复能力。心脏移植的血管生成EOCs从健康受试者显着增加新血管形成和改善心脏功能，而没有这样的效果，从CHF患者的血管生成EOCs移植后观察。实时聚合酶链反应分析14个候选angiomiR，在血管生成EOC中表达，显示在CHF患者的血管生成EOC中angiomiR-126和-130a明显丢失，在循环CD 34（+）细胞中也观察到了这一点。抗miR-126转染显著损害了来自健康受试者的血管生成EOCs改善心脏功能的能力。miR-126模拟物转染增加了CHF患者血管生成EOCs的能力，以改善心脏新血管形成和功能。结论-本研究揭示了CHF患者血管生成EOCs和循环CD 34（+）细胞中angiomiR-126和-130 a的缺失。降低的miR-126表达被鉴定为限制其改善心脏新血管形成和功能的能力的新机制，所述心脏新血管形成和功能可以通过miR-126模拟转染来靶向。（循环。2012;126：2962-2975）。
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. (Circulation. 2012;126:2962-2975.)