Ratio Of Microparticles To Endothelial Progenitor Cells Is Increased In A Diabetic Population

Diabetes Mellitus (DM) is strongly associated with a high incidence of cardiovascular disease (CVD) although often individuals show no symptoms or signs of disease. Therefore, quantitative measures are needed to distinguish those diabetic patients at higher risk for CV events. Cell derived microparticles (MPs), submicron membrane vesicles released from activated cells, and endothelial progenitor cells (EPCs) are mediators of cellular damage and endothelial reparative capacity respectively. Both are emerging biomarkers of vascular health and have been assessed individually in diabetic populations. To extend on this, we examined whether the relationship of MPs to EPCs could be used as a potential index of vascular pathology. Plasma samples were collected from patients with early-stage (ES, Diagnosis<1yr, n=11, 51±4yrs, 7.2±0.5% HbA1c) and long-term (LT, Diagnosis>5yrs, n=21, 64±3yrs, 7.1±0.3% HbA1c) with type 2 DM and compared to age related healthy volunteers (H, n=18, 57±3yrs, 5.3±0.7% HbA1c). EPCs positive for CD133 + /CD34 + and MP subtypes, AnnexinV + (AnnV + ), platelets (CD41 + ), monocytes (CD14 + ) and endothelial (CD144 + ) were measured by flow cytometry. Pro-coagulant microparticles and quantification of soluble proteins was measured using ELISA based methods. A significant relationship was found between MPs and EPCs which correlated with disease duration (H vs. ES vs. LT). Significant changes of pro-coagulant MPs ( P =0.02) and AnnV + MPs ( P =0.02) were noted. Of particular interest, the ratio of CD144 + MPs/EPC increased dramatically ( P =0.009) followed by ratios of AnnV + ( P =0.01), CD41 + ( P =0.01) and CD14 + ( P =0.03) MPs/EPCs. These indices of compromised vascular function were highest in the LT group despite intensive statin therapy (LDL mg/dL, 109±8 in H, vs. 80±7 in LT, P =0.01). Of note, the ratio of endothelial MPs/endothelial progenitor cells (CD144 + MPs/EPCs) was more informative than CRP and a range of inflammatory mediators. This is the first report of a relationship of MPs and EPCs in DM. This ratio provides a quantitative measurement of both pro-coagulant and endothelial injury and can identify DM patients with potentially increased risk of CV disease.