The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β.
The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β.
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DOI：
10.1002/stem.2810
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Medina RJ
中科院分区：
文献类型：
--
作者：
Chambers SEJ;O'Neill CL;Guduric-Fuchs J;McLoughlin KJ;Liew A;Egan AM;O'Brien T;Stitt AW;Medina RJ
髓样血管生成细胞（MAC）通过旁分泌释放血管生成因子促进血管再生，并已被用作许多缺血性疾病的治疗细胞。然而，它们的促血管生成特性已被认为在糖尿病中减弱。本研究探讨糖尿病环境如何影响MAC的免疫表型和功能。使用从糖尿病病症分离的MAC和暴露于糖尿病环境的健康细胞来确定MAC作为糖尿病相关缺血的细胞疗法的潜力。从人外周血中分离MAC，并与促炎巨噬细胞M（LPS + IFNγ）和促血管生成巨噬细胞M（IL 4）一起表征。使用体外3D小管生成试验评估MAC对高D葡萄糖的功能变化。通过基因和蛋白表达分析确定表型变化。此外，从1型糖尿病（T1 D）患者和相应的对照MAC分离和表征。我们的证据表明，MAC身份作为一个独特的巨噬细胞亚型，共享M2促血管生成的特点，但可以区分的CD 163 hi表达。高D-葡萄糖处理显著降低了MAC的促血管生成能力，这与IL 1 β mRNA和蛋白表达的显著增加有关。抑制IL 1 β可消除高d-葡萄糖诱导的抗血管生成作用。与无微血管并发症的T1 D患者或非糖尿病志愿者相比，从有微血管并发症的T1 D患者分离的MAC中IL 1 β也显著上调。这项研究表明，1型糖尿病和糖尿病样疾病损害了MAC的促血管生成和再生能力，这种反应是由IL-1β介导的。干细胞2018;36：834-843
Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their proangiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs. Both MACs isolated from diabetic conditions and healthy cells exposed to a diabetic environment were used to determine the potential of MACs as a cell therapy for diabetic‐related ischemia. MACs were isolated from human peripheral blood and characterized alongside proinflammatory macrophages M (LPS + IFNγ) and proangiogenic macrophages M (IL4). Functional changes in MACs in response to high‐d‐glucose were assessed using an in vitro 3D‐tubulogenesis assay. Phenotypic changes were determined by gene and protein expression analysis. Additionally, MACs from type 1 diabetic (T1D) patients and corresponding controls were isolated and characterized. Our evidence demonstrates MACs identity as a distinct macrophage subtype that shares M2 proangiogenic characteristics, but can be distinguished by CD163hi expression. High‐d‐glucose treatment significantly reduced MACs proangiogenic capacity, which was associated with a significant increase in IL1β mRNA and protein expression. Inhibition of IL1β abrogated the antiangiogenic effect induced by high‐d‐glucose. IL1β was also significantly upregulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or nondiabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic‐like conditions impair the proangiogenic and regenerative capacity of MACs, and this response is mediated by IL‐1β. Stem Cells 2018;36:834–843
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
3.7
作者：
Koh YW;Park CS;Yoon DH;Suh C;Huh J
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Huh J
DOI：
10.1161/atvbaha.110.211581
发表时间：
2010-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Heiss C;Schanz A;Amabile N;Jahn S;Chen Q;Wong ML;Rassaf T;Heinen Y;Cortese-Krott M;Grossman W;Yeghiazarians Y;Springer ML
通讯作者：
Springer ML
DOI：
10.1161/circinterventions.113.001009
发表时间：
2014-04-01
影响因子：
5.6
作者：
de Jong, Renate;Houtgraaf, Jaco H.;Duckers, Henricus J.
通讯作者：
Duckers, Henricus J.
影响因子：
5.7
作者：
Ge, J.;Li, Y.;Zou, Y.
通讯作者：
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