Endothelial Progenitor Cell Dysfunction

TLDR

Type 1 diabetes impairs vascular repair, evidenced by poor wound healing and collateral formation, and endothelial progenitor cells (EPCs) are key regulators of these processes. The study explores whether EPC dysfunction contributes to vascular complications in type 1 diabetes. The authors assessed EPC function via an in vitro angiogenesis assay, revealing impairment in diabetic patients. EPC numbers were 44 % lower in type 1 diabetics, inversely correlated with HbA1c, and their conditioned media had reduced capacity to support endothelial tube formation, indicating persistent functional deficits even under normoglycemic culture conditions.

Abstract

Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA(1c) (R = -0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.