Circulating Endothelial Progenitor Cells Are Reduced in Peripheral Vascular Complications of Type 2 Diabetes Mellitus
Gian Paolo Fadini, MD*,*,
Marta Miorin, BS ,
Monica Facco, BS,
Sondra Bonamico,
Ilenia Baesso, BS,
Franco Grego, MD ,
Mirko Menegolo, MD,
Saula Vigili de Kreutzenberg, MD*,
Antonio Tiengo, MD*,
Carlo Agostini, MD and
Angelo Avogaro, MD, PhD*
* Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padova, School of Medicine, Padova, Italy
Department of Clinical and Experimental Medicine, Clinical Immunology and Hematology, University of Padova, School of Medicine, Padova, Italy
Department of Medical and Surgical Sciences, Division of Vascular Surgery, University of Padova, School of Medicine, Padova, Italy
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Figure 1 Circulating endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) were identified by flow cytometry with low cytoplasmic granularity and with the expression of cell surface antigens, such as CD34 and VEGF-R2 (KDR). (A) Representative flow cytometry analysis of a blood sample from a patient with high EPC count. (B) The number of EPCs from peripheral blood in the four groups of subjects. Mean values ± SE. CTRL = control subjects; NS = not statistacally significant. *p < 0.05.
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Figure 2 (A) Diabetic patients have lower levels of circulating endothelial progenitor cells (EPCs) when compared to controls. Circulating progenitor cells (CPCs) from diabetics display a similar reduction, indicating that the effect of diabetes per se is not specifically targeted to endothelial progenitors. (B) Circulating EPCs and EPC/CPC ratio were negatively correlated with blood glucose at time of blood collection. Higher glucose concentrations were associated with low absolute numbers of EPCs and low endothelial fraction of all progenitors. Mean values ± SE. CTRL = control subjects; DM = diabetes mellitus.
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Figure 3 (A) Effect of individual risk factors on the numbers of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs). (B) In patients fulfilling diagnostic criteria for metabolic syndrome, EPC levels were even lower, while CPCs were reduced to a lesser extent. (C) Linear regression analysis showed a significant negative correlation between the number of risk factors in diabetic patients and their circulating EPC levels. A milder negative correlation with CPC counts was also present. Mean values ± SE. IperCh = hypercholesterolemia; MS = metabolic syndrome; NS = not statistically significant.
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Figure 4 Association between any individual clinical condition present in the study population and variations in endothelial progenitor cell (EPC) and circulating progenitor cell (CPC) levels. Only PVD was associated with significantly reduced EPC numbers, while pathologic AER and microvascular complications had no effect on levels of EPCs and CPCs. Mean values ± SE. AER = albuminuria excretion rate >30 mg per 24 h; CRF = chronic renal failure; NS = not statistically significant.
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Figure 5 (A) Patients with peripheral vascular disease (PVD) had lower levels of endothelial progenitor cells (EPCs) when compared to controls and to non-vascular subjects. In all PVD patients circulating progenitor cells (CPCs) were not significantly lower and thus the EPC/CPC ratio was reduced. Only in diabetic patients with PVD were CPC counts significantly reduced. (B) Linear regression analysis showing correlation between EPCs and CPCs with the ankle brachial index (ABI) in patients with lower extremity vascular disease. The ABI values >1.40 were excluded because they suggest the presence of non-compressible arteries due to calcific sclerosis. (C) Patients with foot lesions due to end-stage lower extremity vascular disease had significantly lower EPC and CPC levels than PVD patients without foot lesions. (D) Circulating EPC numbers and EPC/CPC ratios were higher in PVD patients on statin therapy than in nontreated patients. Mean values ± SE. DM-PVD = diabetic patients with peripheral vascular disease; NS = not statistically significant.
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