Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

ObjectiveThe low number of circulating endothelial progenitor cells (EPCs) has emerged as a biomarker of cardiovascular (CV) risk in adults. Data regarding EPCs in paediatric populations with CV risk factors are limited. The aim of the study was to estimate the EPC number and its relationship with vascular function and structure in children with type 1 diabetes mellitus (T1DM).Design and methodsWe performed a comparative analysis of 52 children with T1DM (mean age 14.5 years; diabetes duration, 6.0 years; HbA1c level, 8.5%) and 36 healthy age- and gender-matched control children. EPCs were identified and analysed by flow cytometry with the use of MABs directed against CD34, CD144 (VE-cadherin) and CD309 (VEGFR-2). sICAM-1, hsCRP, thrombomodulin and adiponectin levels were also assessed. We evaluated vascular function (flow-mediated dilation (FMD)) and structure (carotid intima–media thickness (IMT)) ultrasonographically.ResultsFrequencies of CD34+ cells were similar in both groups (P=0.30). In contrast, frequencies of CD34+VE-cadherin+ cells were significantly higher in diabetic children compared with the healthy group (P=0.003). Similarly, diabetic patients tended to present with higher frequencies of CD34+VEGFR+ cells (P=0.06). FMD was lower (6.9 vs 10.5%, P=0.002) and IMT was higher (0.50 vs 0.44 mm, P=0.0006) in diabetic children. We demonstrated a significant relationship between CD34+VEGFR-2+ cells and BMI (r=0.3, P=0.014), HDL (r=−0.27, P=0.04), sICAM-1 (r=0.47, P=0.023) and FMD (r=−0.45, P<0.001). Similarly, frequencies of CD34+VE-cadherin+ cells were significantly correlated with BMI (r=0.32, P=0.02) and FMD (r=−0.31, P=0.03).ConclusionsWe demonstrated here that increased frequencies of EPCs observed in diabetic children are negatively correlated with endothelial function. Further studies are warranted to assess whether this phenomenon might result from effective mobilisation of EPCs in order to repair damaged endothelium in children at increased risk for atherosclerosis.

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MiR-126, IL-7, CXCR1/2 receptors, inflammation and circulating endothelial progenitor cells: The study on targets for treatment pathways in a model of subclinical cardiovascular disease (type 1 diabetes mellitus)

Journal of Translational Medicine ◽

10.1186/s12967-021-02785-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

David J. Coulson ◽

Sherin Bakhashab ◽

Jevi Septyani Latief ◽

Jolanta U. Weaver

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Inflammatory Cytokines ◽

Endothelial Progenitor ◽

Circulating Endothelial Progenitor Cells ◽

Inflammatory State ◽

Pro Inflammatory Cytokines

Abstract Background Type 1 diabetes (T1DM) is associated with premature cardiovascular disease (CVD) and a pro-inflammatory state whilst the proangiogenic miR-126-3p/-5p may play a role in CVD. Animal studies established miR-126 to be pro-angiogenic. We hypothesised miR-126-3p/-5p are reduced in T1DM whilst pro-inflammatory cytokines are increased. Methods 29 well controlled, T1DM patients without CVD and 20 healthy controls (HCs) were studied. MiR-126-3p/-5p were assayed in plasma and peripheral blood mononuclear cells (PBMCs) whilst Chemokine C-X-C Receptor 1/2 (CXCR1/2) mRNA in PBMCs by real-time quantitative PCR. Cytokines were assayed by the Mesoscale Discovery. Ingenuity Pathway Analysis (IPA) was used to predict target genes, cellular functions and pathological states regulated by miR-126-3p/-5p. IPA generated both direct and indirect causations between different targets and analysed whether these effects would be inhibitory or stimulatory based on the published evidence. Results T1DM patients had a relatively good diabetic control (HbA1c = 7.4 ± 0.7% or 57.3 ± 7.6 mmol/mol). Homeostatic cytokine IL-7, pro-inflammatory cytokines IL-8 and TNF-α, and vascular endothelial growth factor-C (VEGF-C) were increased in T1DM, versus HCs; p = 0.008, p = 0.003, p = 0.041 and p = 0.013 respectively. MiR-126-5p was significantly upregulated in PBMCs in T1DM versus HCs; p = 0.01, but not in plasma. MiR-126-3p was unchanged. CXCR1/2 were elevated in T1DM versus HCs; p = 0.009 and p < 0.001 respectively. MiR-126-5p was positively correlated with CXCR1/2, and with HbA1c whilst negatively correlated with circulating endothelial progenitor cells (CD34+CD133+CD45dim) and fibronectin adhesion assay in a combined group of T1DM patients and HCs; p = 0.028 p = 0.049 p = 0.035 p = 0.047 and p = 0.004 respectively. IPA predicted miR-126-5p to be anti-inflammatory through the inhibition of chemokine C–C motif ligand 27, chymotrypsin-like elastase 2A and IL-7, whilst miR-126-3p had no direct anti-inflammatory effect. Simultaneously IPA predicted IL-7 as the most upstream cytokine target. Conclusions T1DM without apparent CVD or diabetic complications is an inflammatory state characterised not only by raised pro-inflammatory cytokines but also by increased receptor CXCR1/2 and miR-126-5p. MiR-126-5p upregulation may represent a compensatory response. Pro-miR-126-5p therapies or anti-IL-7 therapies may be a new option to reduce both inflammation and CVD risk in T1DM. Further research is required in a large prospective study in patients with T1DM.

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Circulating Endothelial Cells, Circulating Endothelial Progenitor Cells, and Circulating Microparticles in Type 1 Diabetes Mellitus

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618825311 ◽

2019 ◽

Vol 25 ◽

pp. 107602961882531 ◽

Cited By ~ 7

Author(s):

Asmaa M. Zahran ◽

Ismail L. Mohamed ◽

Osama M. El Asheer ◽

Deiaaeldin M. Tamer ◽

Mohamed G. M. Abo-ELela ◽

...

Keyword(s):

Endothelial Cells ◽

Type 1 Diabetes ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Circulating Endothelial Cells ◽

Endothelial Progenitor ◽

Circulating Endothelial Progenitor Cells ◽

Diabetic Children ◽

Circulating Microparticles

Background and Aim: Hyperglycemia in type 1 diabetes (T1D) is accompanied by endothelial cell dysfunction which is known to contribute to the pathogenesis of cardiovascular disorders. The aim of the current study was to explore the profile of circulating endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), endothelial and platelet derived micropaticles (EMPs, PMPs) and total microparticles (TMPs), in T1D children in relation to each other and to the metabolic disorders accompanying T1D. Patients and Methods: Thirty T1D patients and 20 age and sex matched healthy volunteers were assessed for HbA1c level and lipid profile. Quantification of CECs, EPCs, TMPs, EMPs and PMPs was done by flow cytometry. Results: The mean levels of EMPs, PMPs, TMPs and CECs were significantly higher in diabetic children compared to controls. Meanwhile, the levels of EPCs were significantly lower in diabetic children compared to controls. Both PMPs and CECs showed the highest significant differences between patients and controls and their levels were directly related to HbA1c, total cholesterol, LDL and triglycerides. A moderate correlation was observed between the frequency of PMPs and CECs. EPCs revealed negative correlations with both LDL and triglycerides. TMPs were only related to LDL, while EMPs were only related to HbA1c. Conclusion: Although there is disturbance in the levels of EMPs, PMPs, TMPs, CECs and EPCs in type 1 diabetic children compared to the controls, only the levels of PMPs and CECs were closely affected by the poor glycemic control and dyslipidemia occurring in T1D; thus may contribute to a higher risk of cardiovascular diseases.

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