Endothelial Progenitor Cells Counts Research Articles

Deficiency of Endothelial Progenitor Cells Associates with Graft Thrombosis in Patients Undergoing Endovascular Therapy of Dysfunctional Dialysis Grafts.

The deficiency of endothelial progenitor cells has been demonstrated to be associated with cardiovascular events in patients undergoing dialysis. However, their correlation with dialysis graft outcomes remains unknown. The objective of this study was to investigate the relationship between circulating endothelial progenitor cells and dialysis graft outcomes. After excluding 14 patients with acute coronary syndrome, decompensated heart failure or graft thrombosis in the prior three months, a total of 120 patients undergoing dialysis who underwent endovascular therapy of dysfunctional dialysis grafts were prospectively enrolled. Blood was sampled from study subjects in the morning of a mid-week non-dialysis day. Surface makers of CD34, KDR, and CD133 were used in combination to determine the number of circulating endothelial progenitor cells. All participants were prospectively followed until June 2013. The median follow-up duration was 13 months, within which 62 patients experienced at least one episode of graft thrombosis. Patients with graft thrombosis had lower CD34+KDR+ cell counts compared with patients without graft thrombosis (median 4.5 vs. 8 per 105 mononuclear cells, p = 0.02). Kaplan-Meier analysis demonstrated thrombosis-free survival was lower in the low CD34+KDR+ cell count group (30%) than in the high CD34+KDR+ cell count group (61%; p = 0.007). Univariate analysis showed diabetes, high sensitive C-reactive protein, lesion length and CD34+KDR+ cell counts associated with graft thrombosis. Multivariate analyses confirmed an independent association between low CD34+KDR+ cell counts and graft thrombosis (hazard ratio, 2.52; confidence interval, 1.43-4.44; p = 0.001). Our study demonstrated an independent association between low circulating endothelial progenitor cell counts and dialysis graft thrombosis.

Long-term nicotine exposure induces dysfunction of mouse endothelial progenitor cells.

Endothelial progenitor cells (EPCs) have an important role in maintaining endothelial homeostasis. Previous studies reported that smoking has detrimental effects on EPCs; however, recent studies revealed that short-term nicotine exposure may benefit EPCs. As most smokers are exposed to nicotine over an extended time period, the present study aimed to investigate the long-term effects of nicotine on EPCs. Mice were administered nicotine orally for 1, 3 or 6 months. The mice exposed to nicotine for 1 month demonstrated increased EPC counts and telomerase activity and reduced cell senescence compared with control mice, consistent with previous reports. However, long-term nicotine exposure resulted in opposing effects on EPCs, causing decreased counts, functional impairment and reduced telomerase activity. Furthermore, the effects of nicotine exposure were correlated with changes in sirtuins type 1 (SIRT1) protein expression. The current study indicated that long-term nicotine exposure induces dysfunction and senescence of EPCs, which may be associated with impairment of telomerase activity through SIRT1 downregulation. The present results emphasize the necessity of smoking cessation to prevent dysfunction of EPCs.

Modulation of circulating endothelial progenitor cells by erythropoiesis-stimulating agents in patients with chronic kidney disease stage G5 and 5D .

Circulating endothelial progenitor cells (EPCs) play a pivotal role in vasculogenesis and promote angiogenesis by secreting growth factors. Recent studies have suggested that erythropoietin (EPO) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. The aim of this study was to investigate whether two erythropoiesis-stimulating agents (ESAs) modulate vascular-related factors and EPC mobilization in patients with chronic kidney disease stage G5 and dialysis (CKD G5 and 5D). We conducted a 12-week prospective study in 63 patients; 21 patients received recombinant human erythropoietin (rhEPO) (EPO group, 4,565.5±1,994.4IU/week), 21 patients received darbepoetin (DA) (DA group, 40.1±13.8µg/week), and 21 patients received no ESAs (no-ESA group). Vascular mediators, including EPCs, vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), high-sensitivity C-reactive protein, and asymmetric dimethyl arginine, were measured at 0 and 12 weeks. EPCs were measured by flow cytometry as CD45^lowCD34⁺CD133⁺ cells. We also performed a subanalysis of dialysis (5D) patients (n=32) in the three groups. In the EPO group, EPC count increased significantly from 0 to 12 weeks in a dose-dependent manner (r=0.62, p=0.005), and the increase was more conspicuous in the subgroup of dialysis 5D patients. In the DA group, the EPC number did not change at 12 weeks. Neither rhEPO nor DA affected the serum levels of the aforementioned biomarkers other than EPC. ;Conclusion: We speculate that the pleiotropic effects of rhEPO and DA beyond their hematopoietic effects may differ between CKD G5 and 5D patients. .

Circulating osteogenic endothelial progenitor cell counts: new biomarker for the severity of coronary artery disease

BackgroundThere is increasing evidence implying that the early and functionally highly active circulating endothelial progenitor cell (CEPC) phenotype (CD34−/CD133+/KDR+) with osteogenic potential (OCN+) might link between vascular atherosclerotic calcification and mechanisms of bone metabolism. We sought to evaluate the early OCN+ CEPC counts as an independent biomarker for the severity of coronary artery disease (CAD). MethodsPeripheral blood samples were drawn from 593 patients undergoing clinically indicated coronary angiography. CAD severity was assessed by the presence of significant coronary artery stenosis (CAS) as well as an ordinal categorical variable. Subjects were followed for all-cause death over a median follow-up of 40months. ResultsOCN+ early CEPC counts (square-root transformed) were independently associated with the presence of significant CAS [odds ratio (OR) per standard deviation (SD) increment: 1.389, 95% confidence interval [CI]: 1.131 to 1.707, p=0.002). Similar association was observed with an increase in levels of CAS (OR: 1.353, 95% CI: 1.157 to 1.582, p<0.001). There was a weak tendency between OCN+ early CEPC counts and all-cause mortality (p=0.090), whereas the highest decile of OCN+ early CEPC counts had a 2.991-fold increased risk of all-cause death (p=0.047). ConclusionsWe demonstrate for the first time an independent, significant, and strong correlation between OCN+ early CEPC counts and CAD severity. Additionally, very high numbers of OCN+ early CEPC tend to be linked to the risk of all-cause mortality.

Endothelial Progenitor Cells as Prognostic Markers of Preterm Birth-Associated Complications.

Preterm birth is associated with alteration of the vascular tree that can result in disease states such as bronchopulmonary dysplasia and retinopathy of prematurity during the neonatal period and emphysema and hypertension in adulthood. Studies have suggested a potential role for endothelial progenitor cells in the pathophysiology of prematurity‐related complications involving blood vessels; however, this knowledge has never been synthesized. We conducted a systematic review of the published data to examine the characteristics of endothelial progenitor cells in relation to preterm birth in humans. Preterm infants compared with term controls displayed similar or increased circulating/cord blood endothelial progenitor cell counts. However, the preterm endothelial progenitor cells were more vulnerable to exogenous factors such as oxidative stress. A reduced number, in particular of endothelial colony‐forming cells, was associated with bronchopulmonary dysplasia. No studies have examined endothelial progenitor cells beyond the neonatal period. These findings could prove useful in the identification of biomarkers for prognostication or therapeutic strategies for vascular‐related diseases in preterm‐born individuals. Stem Cells Translational Medicine 2017;6:7–13

Diabetic wound healing in a MMP9‐/‐ mouse model

Reduced mobilization of endothelial progenitor cells (EPCs) from the bone marrow (BM) and impaired EPC recruitment into the wound represent a fundamental deficiency in the chronic ulcers. However, mechanistic understanding of the role of BM-derived EPCs in cutaneous wound neovascularization and healing remains incomplete, which impedes development of EPC-based wound healing therapies. The objective of this study was to determine the role of EPCs in wound neovascularization and healing both under normal conditions and using single deficiency (EPC) or double-deficiency (EPC + diabetes) models of wound healing. MMP9 knockout (MMP9 KO) mouse model was utilized, where impaired EPC mobilization can be rescued by stem cell factor (SCF). The hypotheses were: (1) MMP9 KO mice exhibit impaired wound neovascularization and healing, which are further exacerbated with diabetes; (2) these impairments can be rescued by SCF administration. Full-thickness excisional wounds with silicone splints to minimize contraction were created on MMP9 KO mice with/without streptozotocin-induced diabetes in the presence or absence of tail-vein injected SCF. Wound morphology, vascularization, inflammation, and EPC mobilization and recruitment were quantified at day 7 postwounding. Results demonstrate no difference in wound closure and granulation tissue area between any groups. MMP9 deficiency significantly impairs wound neovascularization, increases inflammation, decreases collagen deposition, and decreases peripheral blood EPC (pb-EPC) counts when compared with wild-type (WT). Diabetes further increases inflammation, but does not cause further impairment in vascularization, as compared with MMP9 KO group. SCF improves neovascularization and increases EPCs to WT levels (both nondiabetic and diabetic MMP9 KO groups), while exacerbating inflammation in all groups. SCF rescues EPC-deficiency and impaired wound neovascularization in both diabetic and nondiabetic MMP9 KO mice. Overall, the results demonstrate that BM-derived EPCs play a significant role during wound neovascularization and that the SCF-based therapy with controlled inflammation could be a viable approach to enhance healing in chronic diabetic wounds.

Effect of circulating endothelial progenitor cells on adverse cerebrovascular events in the elderly with ischemic cerebrovascular disease

Objective To investigate the value of endothelial progenitor cells (EPCs) in predicting the prognosis of ischemic cerebrovascular disease and mortality in the elderly. Methods A total of 100 elderly patients with ischemic cerebrovascular disease were recruited from the outpatient medical checkup division of our hospital. Clinical data including age, gender, blood pressure, blood glucose, blood lipids, medical history and medications were collected. Circulating EPCs were identified as cell surface markers CD34/CD133 double-positive cells using flow cytometry analysis. Patients were divided into the low and high groups based on the counts of circulating EPCs. After 18 months of follow-up, we evaluated the occurrence of cerebrovascular events. Results There were no significant statistical differences in age, gender, blood pressure, blood lipids, disease history, risk factors or treatment history between the two groups (all P>0.05). The incidences of first hospitalization and cerebrovascular events were higher in the high group than in the low group (both P 0.05). Conclusions Circulating endothelial progenitor cell levels can be considered as a predictor for ischemic cerebrovascular events in the elderly and may be helpful in early prevention and intervention of ischemic cerebrovascular disease in elderly patients. Key words: Endothelial cells; Stem cells; Cerebrovascular disorders; Prognosis

Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients.

Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.

Alteration of circulating endothelial progenitor cell counts could be an independent predictive factor for response to neoadjuvant chemotherapy in patients with breast cancer

Alteration of circulating endothelial progenitor cell counts could be an independent predictive factor for response to neoadjuvant chemotherapy in patients with breast cancer

Levothyroxine but Not Selenium Increases Endothelial Progenitor Cell Counts in Patients with Hypothyroidism

Background: Hypothyroidism is a common endocrine disease associated with increased oxidative stress, increased cardiovascular (CV) risk, CV events and endothelial dysfunction. Endothelial progenitor cells (EPCs) are a well-known marker of CV risk. Objective: The aim of this work was to ascertain whether hypothyroidism is associated with lower EPC counts and if treatment with levothyroxine (LT4) or selenium (Se) improves EPC counts compared to placebo. Methods: Hypothyroid patients (n = 100) were randomly divided into five groups to receive placebo (group A), LT4 (group B) or Se at doses of 83 µg (group C), 166 µg (group D) or 249 µg (group E) for 3 months. Each group comprised 20 patients: 10 with ‘mild' hypothyroidism and 10 with ‘severe' hypothyroidism. A healthy control group (group F) with 20 euthyroid subjects was also recruited. Subjects had to be free of CV disease, diabetes and drugs that interfere with EPCs. Anthropometric measurements (height, weight, BMI), blood pressure, fasting lipids and EPC analyses were performed at baseline and after 3 months. Results: EPC counts were significantly lower in hypothyroid patients compared to controls. EPCs increased after 3 months of treatment with LT4, but not with Se at any dosage. CD133+ and CD34+ EPC counts were negatively correlated with thyroid-stimulating hormone (TSH; r² = 0.523, p < 0.01 and r² = 0.517, p < 0.01, respectively) and positively correlated with FT4 (r² = 0.394, p < 0.01 and r² = 0.369, p < 0.01, respectively). TSH and FT4 were the only predictors of EPC counts. Conclusions: Hypothyroidism is associated with low EPC counts. Treatment with LT4, but not Se, can improve EPC counts.

EFFECT OF ATORVASTATIN THERAPY IN DIFFERENT DOSES ON ENDOTHELIAL PROGENITOR CELLS AND ANGIOGENIC FACTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

Endothelial progenitor cells (EPC) research is a promising trend in cardiology and angiology, since they are actively involved in the vascular endothelium reparation and angiogenesis. Reduction of EPC counts was demonstrated as an independent predictor of cardiovascular morbidity and mortality. The

A study of Analysis of Endothelial Progenitor cells in Peripheral blood in patients with coronary artery disease

Objective: The study is aimed to analyze endothelial progenitor cells (EPCs) in coronary artery disease and also to identify predictive marker to assess EPCs in the same condition. Background: Endothelial progenitor cells (EPC) predict morbidity and mortality in cardiovascular risk. The ideal way to cure atherosclerosis and the subsequent end organ damage is to restore and rejuvenate the dysfunctional vasculature by induction of EPCs. Methods and Results: EPCs characterized by CD34 and KDR or CD133 markers still in progress to standardize. Hence, current study demonstrates the marker to identify the EPC in peripheral blood of patients with CAD. Flow cytometry used to quantify EPCs in 25 coronary artery disease as confirmed on angiography patients and 25 control subjects without CAD were prospectively enrolled in the study. To identify predictive EPCs in the peripheral blood, we used various combinations of markers like CD34+KDR+CD133+CD45-. We found that CAD patients presented significantly lower levels of EPCs, which expresses the markers CD34+CD45-KDR+ and CD133+CD45-KDR. EPCs which express CD34+CD45-KDR+subpopulation shows higher significant change between CAD and control group (p Conclusion: In conclusion, study indicates that there is a progressive decrease in EPCs levels in CAD patients. Patients with low EPC counts had a higher incidence for cardiovascular events. The level of circulating EPCs with CD34+CD45-KDR+ expression predicts the occurrence of cardiovascular events and may help to identify patients at increased cardiovascular risk. Key words: Atherosclerosis, Endothelial progenitor cells, Bone marrow, Vascular endothelial growth factor.

Prognostic relevance of circulating endothelial progenitor cells in patients with chronic heart failure.

Novel strategies for a tailored risk prediction in chronic heart failure (CHF) are crucial to identify patients at very high risk for an improved patient management and to specify treatment regimens. Endothelial progenitor cells (EPCs) are an important endogenous repair mechanism with the ability to counteract endothelial injury and the possibility of new vessel formation. We hypothesised that exhaustion of circulating EPCs may be a suitable prognostic biomarker in patients with CHF. EPCs, defined as CD34+CD45dimKDR+ cells, were analysed using fluorescence-activated cell sorting. EPCs were measured in 185 patients with CHF including 87 (47 %) patients with ischaemic aetiology and 98 (53 %) patients with non-ischaemic CHF and followed for a median time of 2.7 years. During this period, 34.7 % of patients experienced the primary study endpoint all-cause mortality. EPC count was a significant and independent inverse predictor of mortality with an hazard ratio hazard ratio (HR) per increase of one standard deviation (1-SD) of 0.47 (95 % confidence interval [CI]: 0.35-0.61; p<0.001) and remained significant after multivariable adjustment for a comprehensive set of cardiovascular risk factors and potential confounders with a HR per 1-SD of 0.54 (95 % CI: 0.4-0.73; p<0.001). EPCs further demonstrated additional prognostic information indicated by improvements in C-statistic, net reclassification index and integrated discrimination increment. In conclusion, in our study circulating EPCs turned out as strong and independent inverse predictors of mortality underlining the importance of an impaired endothelial repair mechanism in the pathophysiology and progression of CHF.

Association of endothelial progenitor cells and peptic ulcer treatment in patients with type 2 diabetes mellitus.

The present study aimed to investigate the association between endothelial progenitor cells (EPCs) and peptic ulcers in patients with or without type 2 diabetes mellitus (T2DM), in association with the efficiency of peptic ulcer treatment. The study recruited healthy subjects and peptic ulcer patients with or without T2DM. All the ulcer patients, including those with and without T2DM, were administered omeprazole for 8 weeks. Peptic ulcer patients with T2DM were additionally treated with glipizide and novolin. Blood samples were then obtained from the three groups following ulcer treatment. CD133+ cells were isolated from the blood samples using magnetic bead selection, and cultured in complete medium 199. Morphological and quantity changes in EPCs were observed by light and fluorescence microscopy. In addition, flow cytometric analysis was used to quantify the number of vascular endothelial cells. The treatment was partially effective in 7 of the 32 peptic ulcer patients without T2DM and 12 of the 32 peptic ulcer patients with T2DM. However, this treatment was ineffective in 20 of the 32 peptic ulcer patients with T2DM. Notably, 25 peptic ulcer patients without T2DM were defined as completely recovered following treatment. In addition, the number of circulating EPCs as well as their colony forming ability was significantly reduced (P<0.05) in the peptic ulcer patients with T2DM following ulcer treatment, compared with the other groups. Circulating EPC counts were significantly increased in peptic ulcer patients without T2DM, as compared with the healthy controls. With regards to colony formation, peptic ulcer patients without T2DM did not exhibit improved colony formation ability. In conclusion, the number of circulating EPCs and their colony-forming ability was significantly reduced in peptic ulcer patients with T2DM following ulcer treatment when compared with the other groups. This suggests that the poor curative effect of peptic ulcer treatment in these patients is associated with impairment of EPCs.

Endothelial Progenitors and Blood Microparticles: Are They Relevant to Heart Failure With Preserved Ejection Fraction?

Endothelial Progenitors and Blood Microparticles: Are They Relevant to Heart Failure With Preserved Ejection Fraction?

Endothelial Progenitor Cells (EPC) Count by Multicolor Flow Cytometry in Healthy Individuals and Diabetes Mellitus (DM) Patients.

The present study aimed to determine circulating Endothelial Progenitor Cell (EPC) counts by multicolor flow cytometry in healthy individuals and diabetic subjects by means of forming an analysis procedure using a combination of monoclonal antibodies (moAbs), which would correctly detect the circulating EPC count. The circulating EPC count was detected in 40 healthy individuals (20 Female, 20 Male; age range: 26 - 50 years) and 30 Diabetes Mellitus (DM) patients (15 Female, 15 Male; age range: 42 - 55) by multicolor flow cytometry (FCM) in a single-tube panel consisting of 5 CD45/CD31/CD34/CD309/ SYTO® and 16 monoclonal antibodies. Circulating EPC count was 11.33 (7.89 - 15.25) cells/µL in the healthy control group and 4.80 (0.70 - 10.85) cells/µL in the DM group. EPC counts were significantly lower in DM cases that developed coronary artery disease (53.3%) as compared to those that did not (p < 0.001). In the present study, we describe a method that identifies circulating EPC counts by multicolor flow cytometry in a single tube and determines the circulating EPC count in healthy individuals. This is the first study conducted on EPC count in Turkish population. We think that the EPC count found in the present study will be a guide for future studies.

Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1), amlodipine (2.5 mgkg−1 day−1), or vehicle by gavage (n = 20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease.

Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

Circulating endothelial progenitor cells in obese children and adolescents

ObjectiveThis study aimed to investigate the relationship between circulating endothelial progenitor cell count and endothelial activation in a pediatric population with obesity. MethodsObservational and transversal study, including 120 children and adolescents with primary obesity of both sexes, aged 6–17 years, who were recruited at this Cardiovascular Risk Clinic. The control group was made up of 41 children and adolescents with normal body mass index. The variables analyzed were: age, gender, body mass index, systolic and diastolic blood pressure, high‐sensitivity C‐reactive protein, lipid profile, leptin, adiponectin, homeostasis model assessment‐insulin resistance, monocyte chemoattractant protein‐1, E‐selectin, asymmetric dimethylarginine and circulating progenitor endothelial cell count. ResultsInsulin resistance was correlated to asymmetric dimethylarginine (ρ=0.340; p=0.003), which was directly, but weakly correlated to E‐selectin (ρ=0.252; p=0.046). High sensitivity C‐reactive protein was not found to be correlated to markers of endothelial activation. Systolic blood pressure was directly correlated to body mass index (ρ=0.471; p<0.001) and the homeostasis model assessment‐insulin resistance (ρ=0.230; p=0.012), and inversely correlated to adiponectin (ρ=−0.331; p<0.001) and high‐density lipoprotein cholesterol (ρ=−0.319; p<0.001). Circulating endothelial progenitor cell count was directly, but weakly correlated, to body mass index (r=0.211; p=0.016), leptin (ρ=0.245; p=0.006), triglyceride levels (r=0.241; p=0.031), and E‐selectin (ρ=0.297; p=0.004). ConclusionCirculating endothelial progenitor cell count is elevated in obese children and adolescents with evidence of endothelial activation, suggesting that, during infancy, endothelial repairing mechanisms are present in the context of endothelial activation.

Endothelial progenitor cells as a biological marker of peripheral artery disease.

The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.