Endothelial dysfunction underlies the increased cardiovascular disease burden in diabetic patients. Endothelial progenitor cell (EPC) function seems to be defective in these patients. Pioglitazone has been shown to improve the number and function of EPCs and to decrease cardiovascular mortality in the diabetic population.
To determine the adhesive capacity of cultured EPCs on arteries from diabetic and non-diabetic patients and evaluate the effects of high glucose and pioglitazone on this parameter.
EPCs were isolated from mononuclear cells from buffy coats, obtained from healthy blood donors. The cells were plated on fibronectin and were cultured in a microvascular medium. EPCs were labelled with <sup>111sup>In-oxine and adhesion was assessed using a flow chamber in which internal mammary arteries obtained from cardiac surgery were set. CXCR-4 expression was measured by flow cytometry.
EPC adhesion was higher on internal mammary arteries obtained from diabetic patients. Adhesion was decreased after incubation of the EPCs with glucose at 15 mM and was restored by co-incubation with pioglitazone 1 渭M. Glucose at 15 mM decreased CXCR-4 expression and pioglitazone 1 渭M was able to restore it.
Although arteries from diabetic patients possess a higher capacity to adhere EPCs, hyperglycemia decreases the adhesive properties of these cells. This deficiency could be corrected by drugs such as pioglitazone, which are able to modulate CXCR-4 expression and EPC adhesiveness.