The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β

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 pro-angiogenic 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 to determine the potential of MACs as a cell therapy for diabetic-related ischaemia. MACs were isolated from human peripheral blood and characterized alongside pro-inflammatory macrophages M (LPS+IFNγ) and pro-angiogenic 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 pro-angiogenic characteristics, but can be distinguished by CD163hi expression. High-D-glucose treatment significantly reduced MACs pro-angiogenic capacity, which was associated with a significant increase in IL1β mRNA and protein expression. Inhibition of IL1β abrogated the anti-angiogenic effect induced by high-D-glucose. IL1β was also significantly up-regulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or non-diabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic-like conditions impair the pro-angiogenic and therefore regenerative capacity of MACs, and this response is mediated by IL-1β. This article is protected by copyright. All rights reserved.