Background and aims: Vessel health status may result from the balance between endothelial insult and injury repair. The balance between Endothelium derived Microparticles (EdMPs) and Endothelial Progenitor Cells (EPCs) has been proposed to reflect the concomitant processes of endothelial injury and vascular repair capacity. A deeper understanding of the mechanisms involved in the regulation of such a balance is crucial to improve the quantification of the cardiovascular risk. In this study we describe the changes in circulating EPCs, circulating EdMPs and the EdMPs/EPCs ratio across the progression of Type 2 diabetes mellitus (T2DM). Materials and methods: Circulating EdMPs (CD42-CD31+) and circu- lating EPCs (CD34+CD133+KDR+) were quantified by flow cytometric (FACS) analysis (M±SD) in the following four subjects categories: 196 individuals with T2DM (age 61.7±8.8 years, diabetes duration 28.1±11.8 years, BMI 30.8±6.1 kg/m2, HbA1c 7.3±1.2%); 30 newly-diagnosed T2DM (nT2D; 54.8±9.5 years, BMI 29.5±5.2 kg/m2, HbA1c 11.1 ±2.3%); 20 individuals with pre-diabetes (pT2D; 53.8±8.8 years, BMI 29.7±7.7 kg/m2, HbA1c 5.9±0.2%) and 20 healthy controls (C, age 52.1 ±8.9 yrs, BMI 24.1±1.8 kg/m2, HbA1c 5.5±0.3%). Results: Compared to control subjects (Krukal-Wallis non-parametric test), stem cells (CD34+ and CD34+CD133+: 2193±707 and 967±380 cells/ml, respectively) were marginally reduced in pT2D (1742±517 and 841±488 cells/ml, respectively) and nT2D (1686±979 and 796 ±496 cells/ml; p=0.028 and p=0.070 vs T2DM, respectively), but not in T2DM (2212±1262 and 1067±797 cells/ml, respectively). On the contrary, EPCs (CD34+KDR+ and CD34+CD133+KDR+) progressively dropped from C (879±354 and 435±227 cells/ml) to pT2D (590±277 and 302±191 cells/ml), nT2D (496±487 and 263±282 cells/ml) and T2DM (408±338 and 222±207; p<0.001 and p=0.003, respectively). EdMPs increased, though in a not significant manner, from C (7903 ±2501 n/ml), to pT2D (11664±8050 n/ml) and T2DM (11261±15979 n/ml) to nT2D (14843±27238 n/ml). Therefore, EdMPs/EPCs ratio pro- gressively increased from C (21.6±13.2) to pT2D, nT2D (55.0±46.9 and 56.9±50.5, respectively) and T2DM individuals (85.2±148.5; p=0.016 vs. C). By logistic regression analysis, crude odds ratios (ORs) for CD34+CD133+KDR+ cells below the median were 13.0 for nT2D (p=0.012) and 15.2 for T2DM (p=0.009) with ORs, covariated for gender, age, BMI, blood pressure, lipids, blood glucose, HbA1c, urinary albumin to creatinine ratio and CKD-EPI eGFR of 9.8 (p=0.048) and 9.0 (p=0.040), respectively; crude OR for EdMPs/EPCs above the median were 8.7 for nT2D (p=0.014) and 6.3 for T2D (p=0.019) with covariated ORs of 3.1 (ns) and 6.9 (p=0.029), respec- tively. Covariates showed no independent effects even when subjects category was removed from the regression.

Circulating Endothelial Cells (EPC) and Endothelium-derived Microparticles (EdMPs) time-course throughout the natural history of type 2 diabetes

D. Lucchesi;L. Giusti;M. Garofolo;G. Daniele;A. Dardano;R. Miccoli;G. Penno;S. Del Prato
2017-01-01

Abstract

Background and aims: Vessel health status may result from the balance between endothelial insult and injury repair. The balance between Endothelium derived Microparticles (EdMPs) and Endothelial Progenitor Cells (EPCs) has been proposed to reflect the concomitant processes of endothelial injury and vascular repair capacity. A deeper understanding of the mechanisms involved in the regulation of such a balance is crucial to improve the quantification of the cardiovascular risk. In this study we describe the changes in circulating EPCs, circulating EdMPs and the EdMPs/EPCs ratio across the progression of Type 2 diabetes mellitus (T2DM). Materials and methods: Circulating EdMPs (CD42-CD31+) and circu- lating EPCs (CD34+CD133+KDR+) were quantified by flow cytometric (FACS) analysis (M±SD) in the following four subjects categories: 196 individuals with T2DM (age 61.7±8.8 years, diabetes duration 28.1±11.8 years, BMI 30.8±6.1 kg/m2, HbA1c 7.3±1.2%); 30 newly-diagnosed T2DM (nT2D; 54.8±9.5 years, BMI 29.5±5.2 kg/m2, HbA1c 11.1 ±2.3%); 20 individuals with pre-diabetes (pT2D; 53.8±8.8 years, BMI 29.7±7.7 kg/m2, HbA1c 5.9±0.2%) and 20 healthy controls (C, age 52.1 ±8.9 yrs, BMI 24.1±1.8 kg/m2, HbA1c 5.5±0.3%). Results: Compared to control subjects (Krukal-Wallis non-parametric test), stem cells (CD34+ and CD34+CD133+: 2193±707 and 967±380 cells/ml, respectively) were marginally reduced in pT2D (1742±517 and 841±488 cells/ml, respectively) and nT2D (1686±979 and 796 ±496 cells/ml; p=0.028 and p=0.070 vs T2DM, respectively), but not in T2DM (2212±1262 and 1067±797 cells/ml, respectively). On the contrary, EPCs (CD34+KDR+ and CD34+CD133+KDR+) progressively dropped from C (879±354 and 435±227 cells/ml) to pT2D (590±277 and 302±191 cells/ml), nT2D (496±487 and 263±282 cells/ml) and T2DM (408±338 and 222±207; p<0.001 and p=0.003, respectively). EdMPs increased, though in a not significant manner, from C (7903 ±2501 n/ml), to pT2D (11664±8050 n/ml) and T2DM (11261±15979 n/ml) to nT2D (14843±27238 n/ml). Therefore, EdMPs/EPCs ratio pro- gressively increased from C (21.6±13.2) to pT2D, nT2D (55.0±46.9 and 56.9±50.5, respectively) and T2DM individuals (85.2±148.5; p=0.016 vs. C). By logistic regression analysis, crude odds ratios (ORs) for CD34+CD133+KDR+ cells below the median were 13.0 for nT2D (p=0.012) and 15.2 for T2DM (p=0.009) with ORs, covariated for gender, age, BMI, blood pressure, lipids, blood glucose, HbA1c, urinary albumin to creatinine ratio and CKD-EPI eGFR of 9.8 (p=0.048) and 9.0 (p=0.040), respectively; crude OR for EdMPs/EPCs above the median were 8.7 for nT2D (p=0.014) and 6.3 for T2D (p=0.019) with covariated ORs of 3.1 (ns) and 6.9 (p=0.029), respec- tively. Covariates showed no independent effects even when subjects category was removed from the regression.
2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1040982
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