Endothelial Progenitor Cells Levels Research Articles

P4295Pre-procedural administration of sevoflurane increases the levels of endothelial progenitor cells in patients undergoing coronary angioplasty

P4295Pre-procedural administration of sevoflurane increases the levels of endothelial progenitor cells in patients undergoing coronary angioplasty

Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist.

Progesterone (P4) has the potential therapeutic effects for traumatic brain injury (TBI) whose recovery depended on the enhanced angiogenesis. Endothelial progenitor cell (EPC) plays an essential role in vascular biology. We previously demonstrated that P4 administration improved circulating EPC level and neurological recovery of rat with TBI. Here, we hypothesized that P4 augmented angiogenic potential of EPC and the angiogenesis-related neurorestoration after TBI through classical progesterone receptor (PR). EPC derived from rats were stimulated with graded concentrations (0, 10-10 , 10-9 , 5×10-9 , 10-8 , 10-7 mol/L) of P4 or 10-6 mol/L ulipristal acetate (UPA, a PR antagonist). Male rats were subjected to cortical impact injury and treated with (i) DMSO (dimethyl sulfoxide), (ii) P4 and (iii) P4 and UPA. It showed that P4 improved the angiogenic potential of EPC, including tube formation, adhesion, migration and vascular endothelial growth factor secretion, in a dose-dependent fashion with the maximal effect achieved at 10-9 mol/L P4. High concentration (10-7 mol/L) of P4 impaired the angiogenic potential of EPC. Notably, 10-6 mol/L UPA antagonized the stimulatory effects of 10-9 mol/L P4. After administrating P4, a significant improvement of neurological function and the restoration of the leaked blood-brain barrier were observed as well as a reduction of the brain water content. Both vessel density and expression of occludin of vessels were increased. When UPA was administered with P4, the neural restoration and angiogenesis were all reversed. Western blot showed that 10-9 mol/L P4 increased the content of PRA and PRB of EPC, while 10-7 mol/L P4 reduced the content of both PR isoforms, but there was no change found in the TBI rats. It may suggest that P4-mediated angiogenic activity of EPC and angiogenesis in TBI rats were antagonized by PR antagonist.

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study.

Increased non high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol levels are independent risk factors for cardiovascular (CV) mortality with no documented threshold. A new combination of nutraceuticals (berberine 200 mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg) with additive lipid-lowering properties has become available. The aim of the study is to test the efficacy of the nutraceutical formulation (one daily) in lowering non-HDL cholesterol vs. placebo at 12 weeks in individuals with non-HDL-cholesterol levels ≥160 mg/dL. 39 subjects (age 52 ± 11 years; 54% females; body mass index 27 ± 4 kg/m2) were randomized (3:1) in a double blind phase II placebo-controlled study. At baseline, 4 and 12 weeks main clinical/biohumoral parameters, pro-inflammatory cytokines, (gut)-hormones, proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and endothelial progenitor cell (EPC) number were assessed. Baseline characteristics were comparable in the two groups. The intervention significantly decreased non-HDL cholesterol (−30 ± 20 mg/dL; p = 0.012), LDL cholesterol (−31 ± 18 mg/dL, p = 0.011) and apolipoprotein (Apo) B (−14 ± 12 mg/dL, p = 0.030) levels compared to the placebo. Pro-inflammatory, hormonal, PCSK9 and EPC levels remained stable throughout the study in both groups. The intervention was well tolerated. Three adverse events occurred: Epstein Barr virus infection, duodenitis and asymptomatic but significant increase in creatine phosphokinase (following intense physical exercise) which required hospitalization. The tested nutraceutical formulation may represent a possible therapeutic strategy in dyslipidemic individuals in primary prevention.

Impact of statin therapy intensity on endothelial progenitor cells after percutaneous coronary intervention in diabetic patients. The REMEDY-EPC late study

BackgroundA low number (that is, ≤0.0038 per 100 peripheral mononuclear cells) of circulating endothelial progenitor cells (EPC) is common in diabetic patients. Statins increase EPC levels. It is unclear whether intensity of statin therapy has a different impact on EPC levels. MethodsDiabetic patients undergoing drug-eluting stent (DES) implantation were randomized to 1) High intensity statin therapy (atorvastatin 80mg/day; n=66) or 2) Moderate intensity statin therapy (atorvastatin 20mg/day; n=64). EPC levels were assessed at baseline, 24h and 3months. Endpoints assessed at 3months were 1) changes in the proportion of patients with low EPC levels, and 2) uncovered struts rate and neointima growth evaluated by optical coherence tomography. ResultsLow EPC levels rate significantly decreased in the High intensity statin therapy group (from 31.7% to 12.7%; p=0.017) but not in the Moderate intensity statin therapy group (from 25.5% to 21.8%; p=0.81). Uncovered struts rate was similar in the 2 groups (2.4±2.6% vs 2.3±2.2%; p=0.82), whereas mean neointima area and volume were lower in the High intensity statin therapy group (0.68±0.69 vs 1.22±1.29mm2; p=0.001; and, respectively, 13.10±5.77 vs 20.19±24.08mm3; p=0.042). ConclusionsIn diabetic patients, a high intensity statin therapy 1) significantly increases EPC levels and decreases in-stent neointima area and volume, and 2) does not have an impact on the degree of stent re-endothelialization at 3months after DES implantation.

The relationship between serum uric acid level and concentration of proangiogenic endothelial progenitor cells in chronic heart failure patients

Serum uric acid (SUA) is considered as a marker of nature progression of chronic heart failure (CHF) mediated cardiovascular remodeling. Progression of CHF associates with declining of circulating endothelial progenitor cells (EPCs) in the peripheral circulation. t he objective of this study: to establish predictive relationship between the content of uric acid in the blood and the level of circulating endothelial progenitor cells in patients with CHF of ischemic origin. Methods: The study population was structured retrospectively in 126 subjects (54 male), aged 48 to 62 years, with mild-to-severe ischemic CHFSUA level was measured by enzymatic methods, NT-pro-BNP level was examined by immunoelectrochemiluminesence method. EPCs were determined as CD 34 + cells by the flowcytometric technique using High-Definition Fluorescence Activated Cell Sorter methodology. All biomarkers were measured at baseline. The study was approved by an institutional review committee. Results: Concentrations of SUA were distributed by quartiles (Me; IQR): QI=201,1 (190,6; 223,3) umol/l; QII=275,3 (232,0; 311,0) umol/l; QIII=358,0 (320,0; 390,0) mmol/l; and QIV=449,0 (400,0; 496,0) umol/l. We found an independent impact of SUA on counts of CD14 + CD309 + EPCs (r=-0.388; P=0.001) and CD14 + CD309 + Tie2 + MPCs (r=-0.414; P=0.001), but on CD45 + CD34 + EPCs (r=-0.214; P=0.22) and CD45 - CD34 + MPCs (r=-0.16; P=0.16) did not. Cox proportional adjusted Odds Ratios analyses for CD14 + CD309 + and CD14 + CD309 + Tie2 + EPCs by SUA Quartiles (Q) has showed that high Q (Q3 and Q4) of SUA versus low Q (Q1 and Q2) associated with increased risk of depletion of both CD14 + CD309 + and CD14 + CD309 + Tie2 + EPCs. The ROC analysis showed that there was the cut-off point for the SUA level with the best prognostic potential on the risk of decreasing EPCs in both models equal 315,0 umol/l. Conclusion: Circulating level of proangiogenic EPCs phenotyped as CD14 + CD309 + and CD14 + CD309 + Tie2 + is declined progressively depended on quartiles of SUA level in CHF subjects.

Endothelial vascular markers in coronary surgery.

Coronary heart disease is associated with high morbidity andmortality. Endothelial dysfunction in affected patients is linked to long-term atherosclerotic disease progression and cardiovascular event rates. The present paper reports on changes in the levels of endothelial progenitor cells (VEGFR2/CD133/CD34), essential for endothelial repair, and of endothelial microvesicles (CD31/annexin V) as indicators of endothelial lesion, in patients undergoing coronary bypass surgery with respect both to baseline levels and to counts in healthy subjects. In an observational descriptive study, 31 patients scheduled for coronary revascularization surgery were compared with those of 25 healthy controls. In a subsequent longitudinal study, patients undergoing surgery were monitored at5 timepoints up until 48h after surgery. Endothelial progenitor cell (VEGFR2/CD133/CD34) and endothelial microvesicle (CD31/annexin V) levels were quantified by flow cytometry. Baseline endothelial progenitor cell counts in coronary patients were significantly lower than those of healthy controls (p<0.001); however, after surgery, levels rose steadily over all 5timepoints to 48h with statistically significant differences (p<0.001) between intra-operative and 48h after surgery (T5). Endothelial microvesicle levels were significantly higher in coronary patients prior to surgery than in healthy controls (p<0.001), and despite declining at 48h remained significantly higher than those of controls (p<0.001). Coronary surgery has hada positive impact on the endothelium in the patients, prompting a decrease in signs of endothelial dysfunction and a considerable improvement in the endothelial repair mechanisms involved in angiogenesis, playing an important role in the inflammatory response and the remodelling process of ischemic myocardium in postoperative period.

Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation

BackgroundCardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin-converting enzyme inhibitors (ACEIs) may retard the development of CAV but have not been well studied after HT. ObjectivesThis study tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT. MethodsIn this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to undergo ramipril or placebo therapy. They underwent coronary angiography, endothelial function testing; measurements of fractional flow reserve (FFR) and coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR); and intravascular ultrasonography (IVUS) of the left anterior descending coronary artery, within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year. ResultsPlaque volumes at 1 year were similar between the ramipril and placebo groups (162.1 ± 70.5 mm3 vs. 177.3 ± 94.3 mm3, respectively; p = 0.73). Patients receiving ramipril had improvement in microvascular function as shown by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3; p = 0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5; p = 0.017), from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0; p = 0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2; p = 0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group. ConclusionsRamipril does not slow development of epicardial plaque volume but does stabilize levels of endothelial progenitor cells and improve microvascular function, which have been associated with improved long-term survival after HT. (Angiotensin Converting Enzyme [ACE] Inhibition and Cardiac Allograft Vasculopathy; NCT01078363)

Increased Endothelial Progenitor Cell Number in Early Stage of Endometrial Cancer.

It is generally believed that circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) reflect the state of the endothelium, its injury and/or repair possibilities. In different types of cancers, increased numbers of CECs and EPCs were found, suggesting their participation in cancer angiogenesis. The objective of this study was to determine whether, in the blood circulation of women with early endometrial cancer, CEC and EPC levels differ from those of healthy women of similar age. For CEC number evaluation, samples of peripheral blood cells of women with endometrial carcinoma and control subjects were labeled with anti-CD31 and anti-CD45 antibodies; for EPCs, with anti-VEGFR2 (vascular-endothelium growth factor receptor 2)/KDR and anti-CD34 antibodies. The CEC and EPC cells were then quantified by flow cytometry. Endothelial progenitor cell numbers (CD34, VEGFR2/KDR) in the peripheral blood of women with endometrial carcinoma were significantly augmented as compared with those of control healthy women and CEC numbers (CD31, CD45) were similar in both groups. Cancer patients were divided according to the grading into G1 and G2 groups and according to the stage into International Federation of Gynecology and Obstetrics (FIGO) stage IA and FIGO IB groups. Statistically significant augmented EPC numbers were demonstrated only in G1 and FIGO IA patients. These results strongly suggest new vessel formation from recruited endothelial precursors as being involved mainly at the early stages of tumor progression.

Endothelial progenitor cells and vascular endothelial growth factor after endovascular interventions in patients with type 2 diabetes

Aim. To study the quantity of endothelial progenitor cells (EPCs) and levels of vascular endothelial growth factor A (VEGF-A) in patients with type 2 diabetes mellitus (T2DM) after endovascular interventions on coronary and peripheral arteries.&#x0D; Materials and methods. We observed 68 patients with stable angina pectoris and critical limb ischaemia, admitted for elective percutaneous coronary intervention and endovascular revascularisation of the lower extremity. The number of CD34+VEGFR2+CD45- and CD34+CD133+CD45- cells and levels of VEGF-A were determined before endovascular intervention and 24 days after the surgery.&#x0D; Results. We found that in patients without diabetes, the levels of EPCs increased significantly after endovascular interventions (CD34+VEGFR2+CD45-cells, p 0.0001; CD34+ CD133+CD45-cells p = 0.041). The levels of EPCs in the peripheral blood of patients with T2DM before and after endovascular interventions did not significantly differ. The analysis of VEGF-A showed a statistically significant increase after intervention in both groups. In addition, in patients with an HbA1c level of 8% and duration of diabetes of 10 years, the levels of EPCs significantly increased (p = 0.001 and 0.005, respectively). In patients with an HbA1c level of 8% and duration of diabetes of 10 years, the levels of EPCs before and after endovascular interventions did not significantly differ.&#x0D; Conclusions. Patients with diabetes exhibited impaired EPC mobilisation after endovascular interventions. Poor glycaemic control and a long duration of diabetes are among the risk factors of EPC mobilisation.

Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity

Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes. Hence, we examined the systemic effects of chronic (12 weeks) acrolein exposure at concentrations similar to those found in tobacco smoke (0.5 or 1 ppm). Acrolein exposure in mice led to a 2- to 3-fold increase in its urinary metabolite 3-hydroxypropyl mercapturic acid (3-HPMA) with an attendant increase in pulmonary levels of the acrolein-metabolizing enzymes, glutathione S-transferase P and aldose reductase, as well as several Nrf2-regulated antioxidant proteins. Markers of pulmonary endoplasmic reticulum stress and inflammation were unchanged. Exposure to acrolein suppressed circulating levels of endothelial progenitor cells (EPCs) and specific leukocyte subsets (eg, GR-1+ cells, CD19+ B-cells, CD4+ T-cells; CD11b+ monocytes) whilst other subsets (eg, CD8+ cells, NK1.1+ cells, Ly6C+ monocytes) were unchanged. Chronic acrolein exposure did not affect systemic glucose tolerance, platelet-leukocyte aggregates or microparticles in blood. These findings suggest that circulating levels of EPCs and specific leukocyte populations are sensitive biomarkers of inhaled acrolein injury and that low-level (<0.5 ppm) acrolein exposure (eg, in secondhand smoke, vehicle exhaust, e-cigarettes) could increase CVD risk by diminishing endothelium repair or by suppressing immune cells or both.

Association between echocardiographic epicardial fat thickness and circulating endothelial progenitor cell level in patients with stable angina pectoris.

Epicardial adipose tissue is associated with coronary artery disease (CAD). Circulating endothelial progenitor cell (EPC) level represents a marker of endothelial dysfunction and vascular health. However, the relationship between epicardial fat and circulating EPC remains unknown. This study aimed to investigate association between echocardiographic epicardial fat thickness (EFT) and circulating EPC level. Epicardial fat causes inflammation and contributes to progression of CAD. We enrolled 213 consecutive patients with stable angina, and EFT was determined by echocardiography. Quantification of EPC markers (defined as CD34 + , CD34 + KDR + , CD34 + KDR + CD133 + cells) in peripheral blood samples was used to measure circulating EPCs. All patients were divided into 3 tertiles according to EFT levels: group 1, low tertile of EFT; group 2, middle tertile of EFT; and group 3, high tertile of EFT. Among the 3 groups, CAD disease severity determined by SXscore was negatively correlated with EFT, but the difference did not reach statistical significance (P = 0.066). Additionally, patients in the high and middle tertiles of EFT had higher circulating EPC levels than did those in the low tertile of EFT (P = 0.001 and P < 0.001, respectively). In multivariate analysis, EPC level was significantly associated with echocardiographic EFT (standardized β = -0.233, P = 0.001), independent of multiple covariates. Epicardial adipose tissue is associated with circulating EPC levels. There was a trend between epicardial fat and severity of CAD, though analysis did not reach statistical significance, and this may be attributed to the interaction between several risk factors of CAD.

Endothelial progenitor cells in patients with non-small cell lung cancer

Introduction: Endothelial progenitor cells (EPCs) are known as putative cells in neovasculogenesis during pathological conditions, which are derived from bone marrow. This study was performed to systematically review the EPCs frequency in patients with non-small cell lung cancer (NSCLC) by evaluating the expression of CD133 and vascular endothelial growth factor (VEGF) markers.Methods: We search the PubMed and Scopus databases for the following keywords; CD133 AND lung AND VEGF. Inclusion criteria were all the articles studied the expression of both CD133 and VEGF markers in patients with NSCLC. No language and date restrictions were imposed to the search strategy. All the articles that studied only one biomarker or those that investigated the markers expression and EPCs count in patients with other types of tumors except NSCLC were excluded from the study.Result: Totally 51 articles obtained following the primary search of both databases. Only 7 of them had the eligibility to be included in this systematic review. Six articles were case- control and one was a cohort type of investigation. Flowcytometry and immunohistochemistry were the most applied methods for estimating the EPCs count and evaluating the expression of markers in circulating peripheral blood and tumors tissue. The expression of EPCs markers was increased in patients with NSCLC compared to healthy control individuals; however, the frequency of EPCs was low in peripheral blood of patients.Conclusion: Although it is not clear that circulating EPC numbers are associated with lung cancer patients angiogenesis, EPCs and VEGF levels are elevated in patients with operable NSCLC. The ideal method for evaluating circulating endothelia cells (CECs) or EPCs levels in vivo is still a matter of debate and because of the low number of EPCs in peripheral blood, their detection is technically challenging.

관상동맥질환 환자에게 실시한 수영운동과 걷기운동이 혈류매개 확장반응과 혈관내피전구세포 발현에 미치는 영향

The aim of this study is to effects of swimming exercise and walking exercise for 10 weeks in patients with a coronary-artery disease on their flow mediated dilation (FMD) and the expression level of endothelial progenitor cells (EPCs). A patient group of 18 subjects were recruited, a walking exercise was carried out (n =10), and a swimming exercise was carried out (n = 8). The two exercises are types of the same aerobic exercise preferred by a lot of patients, but there are very insufficient grounds for scientific studies of swimming exercise as compared to those of the walking exercise. For measurement, this study measured their body composition, FMD and EPCs. As a result of this study, it turned out that there were no statistically significant changes in the expression level of EPCs and FMD in the patients with a coronary-artery disease, who carried out the swimming exercise than in those who carried out the walking exercise, but there was an effect between the times after carrying out the two exercises. In this result, since the swimming exercise and the walking exercise are the same aerobic exercises, there were no statistically significant differences, but both exercises had positive effects, so the importance of the exercises was confirmed.

Preserved endothelial progenitor cell angiogenic activity in African American essential hypertensive patients

African American (AA) subjects with essential hypertension (EH) have greater inflammation and cardiovascular complications than Caucasian EH. An impaired endogenous cellular repair system may exacerbate vascular injury in hypertension, yet whether these differ between AA EH and Caucasian EH remains unknown. Vascular repair by circulating endothelial progenitor cells (EPCs) is controlled by regulators of EPC mobilization, homing, adhesion and new vessel formation, but can be hindered by various cytokines. We hypothesized that EPC levels and function would be impaired in AA EH compared with Caucasian EH, in association with increased levels of inflammatory mediators and EPC regulators. CD34+/KDR+ EPCs were isolated from inferior vena cava and renal vein blood samples of AA EH and Caucasian EH patients (n = 18 each) and from peripheral veins of 17 healthy volunteers (HVs) and enumerated using fluorescence-activated cell sorting. Angiogenic function of late-outgrowth endothelial cells expanded from these samples for 3 weeks was tested in vitro. Levels of inflammatory mediators, angiogenic factors and EPC regulators were measured by Luminex. EPC levels were decreased in both AA and Caucasian EH compared with HVs, whereas their late-outgrowth endothelial cell angiogenic function was comparable. Levels of several inflammatory mediators were elevated in AA EH compared with Caucasian EH and HVs. Contrarily, vascular endothelial growth factor and its receptor-2 were lower. EPC levels inversely correlated with blood pressure in all hypertensive patients and estimated glomerular filtration rate with inflammatory mediators only in AA EH. Despite lower EPC numbers, decreased vascular endothelial growth factor signaling and inflammation, EPC function is preserved in AA EH compared with Caucasian EH and HVs, suggesting compensatory mechanisms for vascular repair.

Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes

BackgroundFewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown.MethodsRandomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed.ResultsBaseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers.ConclusionsV exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity.Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013

Deficiency of circulating progenitor cells associated with vascular thrombosis of hemodialysis patients.

Hemodialysis (HD) patients have an increased risk of thrombosis. Endothelial progenitor cells (EPCs), which function in vascular repair, are deficient in HD patients. Nonetheless, the relationship between EPC deficiency and thrombosis in HD patients is unknown. From January 2010 to December 2012, circulating levels of EPCs that were positive for CD34 and kinase insert domain receptor (KDR) were measured in 269 HD patients. Patients received prospective follow-ups at 6-month intervals until May 2015. The primary outcome was the composite of HD access thrombosis and systemic vascular thrombosis. There were 141 thrombotic events, 50 systemic vascular thrombotic events and 116 HD access thrombotic events. We found significantly negative associations between CD34 + KDR + tertile and overall thrombotic events (low: 61%; middle: 56%; high: 40%; P = 0.02), systemic vascular thrombotic events (low: 27%; middle: 18%; high: 10%; P = 0.03) and HD access thrombotic events (low: 52%; middle: 46%; high: 36%; P = 0.02). Univariate analysis indicated that systemic vascular thrombotic events were positively associated with age, diabetes, dyslipidemia, vascular disease history, urea clearance, albumin and C-reactive protein (CRP), and negatively associated with CD34 + KDR + cell count. HD access thrombosis was positively associated with vascular disease history and CRP, and negatively associated with CD34 + KDR + cell count. Multivariate analysis indicated that a low CD34 + KDR + cell count was an independent risk factor for both types of thrombosis. Our study of a population of HD patients showed that a low level of circulating EPCs is associated with thrombosis.

Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke.

Angiogenesis is an important pathophysiological response to cerebral ischemia, and can be modulated by vascular endothelial growth factor (VEGF) and endostatin. Circulating endothelial progenitor cells (EPCs) also play an important role as an endogenous repair mechanism for ischemic injury. We sought to investigate early changes in the expression of VEGF and endostatin in serum and the circulating EPCs in patients with acute ischemic stroke (AIS) and analyzed the relations between them. The peripheral blood and serum samples were obtained from 30 patients at 1, 3, 5 and 7 d after AIS. Flow cytometry was used to quantify EPCs, and VEGF and endostatin were measured by enzyme linked immunosorbent assay. Correlation analysis was performed to assess the relations between them. Receiver operating characteristic (ROC) curve was used to appraise the value of EPCs levels in predicting the 90-day prognosis after AIS. Compared with control subjects, circulating EPCs numbers increased from a very lower initial level (P < 0.001) until 7 d after AIS. Serum VEGF and endostatin levels increased and peaked at 3 d and 5 d post-stroke (both P < 0.001), respectively. A significant correlation (P = 0.001) was found between peak serum VEGF concentration and peak endostatin concentration. VEGF/endostatin ratio at day 1 and day 3 after AIS significantly correlated with circulating EPCs numbers at day 5 (P < 0.001) and day 7 post-stroke (P < 0.001). ROC curve analysis suggested that circulating EPCs number at day 7 had a significantly predictive power for good prognosis. VEGF and endostatin may mediate EPCs proliferation in the early phase of ischemic stroke, and the circulating EPCs levels can be a predictor of clinical outcome in AIS.

Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells (EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.

Relationship of Circulating CXCR4+ EPC with Prognosis of Mild Traumatic Brain Injury Patients

To investigate the changes of circulating endothelial progenitor cells (EPCs) and stromal cell-derived factor-1α (SDF-1α)/CXCR4 expression in patients with mild traumatic brain injury (TBI) and the correlation between EPC level and the prognosis of mild TBI. 72 TBI patients (57 mild TBI, 15 moderate TBI patients) and 25 healthy subjects (control) were included. The number of circulating EPCs, CD34+, and CD133+ cells and the percentage of CXCR4+ cells in each cell population at 1,4,7,14,21 days after TBI were counted by flow cytometer. SDF-1α levels in serum were detected by ELISA assay. The patients were divided into poor and good prognosis groups based on Extended Glasgow Outcome Scale and Activity of Daily Living Scale at 3 months after TBI. Correlation analysis between each detected index and prognosis of mild TBI was performed. Moderate TBI patients have higher levels of SDF-1α and CXCR4 expression than mild TBI patients (P < 0.05). The percentage of CXCR4+ EPCs at day 7 post-TBI was significantly higher in mild TBI patients with poor prognosis than the ones with good prognosis (P < 0.05). HAMA and HAMD scores in mild TBI patients were significantly lower than moderate TBI patients (P < 0.05) in early term. The percentage of CXCR4+ EPCs at day 7 after TBI was significantly correlated with the prognosis outcome at 3 months. The mobilization of circulating EPCs can be induced in mild TBI. The expression of CXCR4+ in EPCs at 7 days after TBI reflects the short-term prognosis of brain injury, and could be a potential biological marker for prognosis prediction of mild TBI.

Lower Levels of Circulating Endothelial Progenitor Cells Are Associated with Increased Recurrence after Unprovoked Venous Thrombosis

Introduction: Endothelial progenitor cells (EPCs) are multipotent progenitor cells mainly residing in human bone marrow. In response to stimuli such as arterial ischaemia or venous thrombosis, EPCs are mobilised from the bone marrow, released into the circulation and home to sites of vascular injury where they promote endothelial regeneration, revascularization, vasoactive and angiogenic factor secretion, proteinase generation and vein wall remodelling. There is significant research interest into the potential therapeutic role of EPCs in vascular injury. However, to our knowledge there is no published data on the measurement of EPCs in a larger population of patients with comparison to thrombotic outcomes and other biomarkers known to be predictive of recurrence risk for example, D Dimer.Methods: The EXACT study is a randomised controlled trial of extended warfarin treatment versus observation only for the prevention of recurrent venous thromboembolism (VTE) and post thrombotic syndrome (PTS) in patients with an unprovoked VTE. Patients recruited to this study had blood samples taken 3 months post VTE event whilst still on warfarin prior to stopping or continuing anticoagulation according to their randomisation group. All patients were clinically followed up for 2 years following randomisation and recurrent thrombotic events (confirmed by imaging) were recorded.The blood samples were processed for Full Blood Count, INR, D Dimers and quantitation of Endothelial Cells by flow cytometry (circulating mature and progenitor). Endothelial cells were identified by low side scatter, weak CD45 (unlike haematopoetic cells) and expression of endothelial markers (CD146, VEGFR, VEGFR-2). Endothelial progenitor cells also demonstrated at least one marker of immaturity (CD34 and CD133). Apoptotic or dead cells were detected and excluded using 7-amino-actinomycin D staining. The number of EPC and circulating endothelial cell (CEC) events was divided by the number of CD45 positive events and multiplied by the total white count, which will give a value x103/microlitre.Results: At 3 months of treatment with warfarin, in 193 patients, samples of sufficient quality were processed by flow cytometry for EPC quantitation. In 182 of these patients, a sufficiently full citrated sample was also available for D Dimer quantitation.High D Dimer levels were associated with low EPC levels and visa versa (fig 1). Out of the 193 patients, during 2 year follow up, 19 patients (10%) went on to have a recurrent VTE.D Dimers at 3 months treatment were not significantly different in patients who had a recurrence versus those who didn’t (Figure 2). There was also no significant difference in circulating mature endothelial cells (CEC) and total WCC (table 2). However, EPC levels were significantly lower in patients who went on to develop a thrombosis vs those who didn’t (p<0.05) figure 3.Discussion: According to current guidelines, patients with unprovoked VTE are considered for long term anticoagulation following a discussion with the patient regarding VTE recurrence risk off treatment vs bleeding risk on treatment. D Dimer results can be helpful to refine the estimated recurrence risk (e.g. using the DASH2 score) but testing is only validated off anticoagulation (for at least 7 days) which can be cumbersome to organise. This study was unable to support the predictive value of D Dimers taken from patients on warfarin.If EPC quantitation from blood samples of patients is confirmed to be predictive of VTE recurrence this could represent a new informative biomarker to aid decision making without the need to interrupt anticoagulation therapy. It also has the potential to provide complimentary information. For example, in defining a truly "low risk" group in those with negative D Dimers after completion of treatment. Further larger studies are needed to confirm the predictive value of EPC quantitation for VTE recurrence in patient groups continuing or discontinuing anticoagulation (this study included both groups) and to confirm whether the same results apply to patients on DOACs. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.