Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures

TLDR

Circulating endothelial progenitor cells (EPCs) are now recognized as key contributors to neovascularization, and their dysfunction may underlie diabetic vascular complications. The study isolated EPCs from 20 type II diabetic patients and 20 age‑matched controls for comparative analysis. Diabetic EPCs proliferated 48 % less, showed reduced adhesion to TNF‑α‑activated HUVECs, were 2.5‑fold less likely to form tubules in Matrigel, and these deficits correlated with hemoglobin A1C, indicating diabetes impairs EPC function relevant to vessel repair.

Abstract

Background— The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology. Methods and Results— EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% ( P <0.01) and inversely correlated with patient levels of hemoglobin A1C ( P <0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-α (TNF-α) ( P <0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls ( P <0.05). Conclusions— These findings suggest that type II diabetes may alter EPC biology in processes critical for new blood vessel growth and may identify a population at high risk for morbidity and mortality after vascular occlusive events.