Endothelial vascular markers in coronary surgery.

Endothelial Progenitor Cells in HIV-Positive Patients

High levels of endothelial progenitor cells and circulating endothelial cells in patients with Behcet’s disease and their relationship to disease activity

Acute myocardial infarction (AMI) and the following heart failure are main causes of disability and death across the globe. Endothelial progenitor cell (EPC) levels are linked to AMI. Herein, we assessed the predictive value of EPCs for post-percutaneous coronary intervention (PCI) ventricular remodeling in AMI patients. This study retrospectively analyzed 215 AMI patients receiving PCI, who were then categorized into the VR ( n = 66) and N-VR ( n = 149) groups as per whether they developed post-PCI ventricular remodeling. Left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and EPCs were measured. The correlations of LVEF and NT-pro-BNP with EPCs, the predictive value of EPCs for post-PCI ventricular remodeling, and the risk of post-PCI ventricular remodeling in AMI patients with different EPC levels were analyzed by Spearman's analysis, receiver-operating characteristic curve, and Kaplan-Meier curve. LVEF and EPC levels were lower and NT-pro-BNP level was higher in the VR group than the N-VR group. EPC levels in the class III-IV group were lower than those in the class I-II group. EPC levels in AMI patients correlated positively with LVEF ( r = 0.683) and negatively with NT-pro-BNP ( r = -0.761). EPCs exhibited high predictive value for post-PCI ventricular remodeling in AMI [area under the curve (AUC) of 0.822] and anterior MI (AUC = 0.941) patients. AMI and anterior MI patients with low EPC levels had a higher risk of post-PCI ventricular remodeling. Low EPC levels have high predictive value for post-PCI ventricular remodeling, and increase the risk of post-PCI ventricular remodeling in AMI patients.

Objective To study the value of circulating endothelial progenitor cell(EPC), stromal cell-derived factor-1α(SDF-1α), vascular endothelial growth factor(VEGF) and nitric oxide(NO) in diagnosis and prediction of in-stent restenosis after primary coronary intervention in elderly patients with old myocardial infarction. Methods Fifty-one elderly patients with restenosis after coronary sent implantation in Huai′an Hospital Affiliated of Xuzhou Medical University after primary coronary intervention from Jan.2007 to Sep.2016 were selected as observation group, 30 cases with the roughness of coronary vessels and without restenosis based on the analysis of coronary arteriography were considered as the control group. The patients in observation group were divided into different groups according to restenosis of vessels, severity of vessel restenosis, left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) . The levels of EPC, SDF-1α, VEGFand NO were measured in the patients. The data were compared by one-way ANOVA and LSD test. Results (1) The 1evels of EPC, SDF-1α, VEGF and NO were decreased along with the increase in the number of restenosis of vessels in elderly patients with old myocardial infarction, the differences were statistically significant(F=140.0, 122.8, 183.8, 515.8; with P values below 0.05). The levels of EPC, SDF-1α, VEGF and NO in patients with multivessel restenosis were lower than that in control group, a single vessel restenosis group and double vessel restenosis group, the differences were statistically significant(with P values below 0.05). (2)Along with severity of vessel restenosis, the levels of EPC, SDF-1α, VEGF and NO were decreased, the differences were statistically significant(F=120.7, 124.9, 107.5, 127.1; with P values below 0.05). The levels of EPC, SDF-1α, VEGF and NO in patients with in-stent restenosis (100%) were (0.3±0.2)%, (3.3±1.3) ng/L, (1.1±0.8) ng/L, (15.1±10.8) μmol/L, lower than that in patients with in-stent restenosis (90%-99%)[(1.1±0.4)%, (5.3±2.7) ng/L, (2.0±0.5) ng/L, (27.8±12.9) μmol/L], the differences were statistically significant(with P values below 0.05). The levels of EPC, SDF-1α, VEGF and NO in patients with in-stent restenosis (100%) were lower than in patients with in-stent restenosis (70%-89%) and the control group, the differences were statistically significant(with P values below 0.05). (3) With the decrease of LVEF, the levels of EPC, SDF-1α, VEGF and NO were decreased, the differences were statistically significant(F=663.0, 1599.0, 720.0, 2188.4; with P values below 0.05). The levels of EPC, SDF-1α, VEGF and NO in the LVEF 25%-36% group were lower than other groups significantly, the differences were statistically significant(with P values below 0.05). (4) Along with the decrease of NYHA, the levels of EPC, SDF-1α, VEGF and NO were decreased, the differences were statistically significant(F=135.1, 118.2, 175.6, 115.2; with P values below 0.05). The levels of EPC, SDF-1α, VEGF and NO in the patients with NYHA Ⅳ group were lower than other groups significantly, the differences were statistically significant(with P values below 0.05). Conclusion EPC, SDF-1α, VEGF and NO may be used as the new diagnostic makers for restenosis after primary coronary stent implantation in elderly patients with old myocardial infarction. Key words: Coronary restenosis; Coronary occlusion; Stents; Myocardial infarction; Diagnosis; Aged; Marker

Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms. The study comprised 348 high-risk patients with prior coronary artery disease, ischemic stroke, and/or diabetes mellitus recruited from medical outpatient clinics and 150 healthy subjects without such a history. PR interval was considered prolonged if >200ms, as determined from resting 12-lead electrocardiogram. Vascular function was assessed by brachial flow-meditated dilatation (FMD) using high-resolution ultrasound. Circulating CD133(+)/KDR(+) endothelial progenitor cell (EPC) levels were measured by flow cytometry. Among healthy subjects, PR interval was inversely associated with FMD (R = -0.20, P = 0.015), but not with the level of circulating CD133(+)/KDR(+) EPC (R = 0.05, P = 0.58). Among high-risk cardiovascular patients, PR prolongation >200ms was more common compared with healthy subjects (45/348 (13%) versus 4/150 (3%), P < 0.001). PR interval was associated inversely with FMD (R = -0.14, P = 0.01) and positively with circulating CD133(+)/KDR(+) EPC level (R = +0.14, P = 0.009). Circulating CD133(+)/KDR(+) EPC level was significantly increased in patients with PR prolongation >200ms (0.87 ± 0.37 versus 0.68 ± 0.42 (log, ×10(-3)/ml), P = 0.005). Adjusted for potential confounders, increased PR interval remained independently associated with increased CD133(+)/KDR(+) EPC by +0.002 (95% confidence interval (CI) 0.000 to 0.004 (log, ×10(-3)/ml), P = 0.011) and depressed FMD (B = -0.014%, 95% CI -0.027 to -0.002, P = 0.026). PR prolongation is associated with endothelial dysfunction and evidence of endothelial repair activation in patients with high cardiovascular risk.

Objective To investigate the correlation of the level of circulating endothelial progenitor cells (EPCs) and cerebral atherosclerosis burden (CAB) in patients with large artery atherosclerotic stroke (LAAS) and its predictive effect for LAAS. Methods Consecutive patients with LAAS and healthy controls were enrolled. Flow cytometry wad used to detect EPC level in peripheral blood. CAB was assessed according to the results of CT angiography or magnetic resonance angiography. Univariate analysis was used to compare the demographic and clinical data in both groups. Multivariate logistic regression analysis was used to identify the correlation of circulating EPC level and LAAS. Results A total of 141 patients with LAAS and 100 controls were enrolled. The constituent ratios of hypertension (65.9% vs. 51.0%; χ2 =5.443, P=0.020) and diabetes (27.0% vs. 16.0%; χ2 =4.035, P=0.045) of the patents, as well as systolic blood pressure (139.1±11.1 mmHg vs. 131.6±15.7 mmHg; t=3.549, P=0.003; 1 mmHg=0.133 kPa) and fasting blood glucose (5.8±2.1 mmol/L vs. 5.2±2.0 mmol/L; t=2.344, P=0.020) in the patient group were significantly higher than those in the control group, while the circulating EPC level (median, interquartile range) (13[3-32] /ml vs. 31[7-59]/ml; Z=3.913, P=0.001) was significantly lower than the control group. Multivariate logistic regression analysis showed that the decreased circulating EPC level (odd ratio 2.632, 95% confidence interval 1.412-4.907, P=0.002) was an independent risk factor for LAAS after adjusting the confounders. The EPC level in the CAB >3 group was significantly lower than that in the CAB 1 group (5 [2-19]/ml vs. 22 [9-43]/ml; Z=3.338, P=0.011). Spearman rank correlation analysis showed that the EPC level was significantly negatively correlated with CAB (r=-0.257, P=0.002). Conclusions The decreased circulating EPC level was an indenpendent risk factor for the onset of LAAS, and the EPC level was negatively correlated with CAB. Key words: Endothelial Progenitor Cells; Stroke; Brain Ischemia; Atherosclerosis; Risk Factors

Introduction: Endothelial progenitor cells (EPC) play an important role in the regeneration of the nervous tissue, blood-brain barrier stabilization and in neovascularization of blood vessels damaged by stroke. The aim of the study was to assess the level of EPC in patients with acute cerebral stroke due to cerebral microangiopathy and the potential dependence with the clinical condition, radiological image and prognosis, both in the ischemic and the haemorrhagic stroke. Methods: 66 patients with lacunar ischemic stroke were included in the prospective study, 38 patients with the “loco typico” haemorrhagic stroke and 22 from the control group without acute/chronic cerebral circulatory disorders. The level of EPC was determined using flow cytometry and identified with the immune-phenotype CD45–, CD34+, CD133+ on the 1 st and 8 th day of stroke. Results: It has been shown a significantly higher level of EPC on the 1 st day of stroke (regardless of aetiology) compared to the control group (med. 17,75 cells/ul (0-488 cells/ul) vs 5,24 cells/ul (0-95 cells/ul); p=0.0006). The level of EPC on day 1 and 8 was correlated with the subgroup of patients with haemorrhagic stroke. A significant correlation was found between the volume of the haemorrhagic focus on the 1 st day and the level of EPC (R= -0.3378, p=0.0471) and the degree of regression of the haemorrhagic focus and the level of EPC (R=-0.3896, p=0.0367). Conclusions: The study showed that endothelial progenitor cells are an early marker of cerebral vascular damage, both in ischemic and haemorrhagic stroke. The research highlights, for the first time, the relationship between the level of EPC and the degree of regression of a haemorrhagic focus. However the prognostic value of EPC for clinical condition and prognosis of stroke patients was not found in the study.

Background: Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design. Methods: The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models. Results: The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p < 0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34+CD133+CD309+cells: r = 0.510, p = 0.001; CD34+ CD133−CD309+cells: r = 0.262, p = 0.004; CD34−CD133+CD309+cells: r = 0.348, p < 0.001). Conclusions: Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke.

Background Arterial atherosclerotic occlusive syndrome remains the leading cause of mortality and morbidity worldwide. Peripheral arterial occlusive disease (PAOD) is a manifestation of atherosclerosis in the lower extremities. In our previous preclinical study, hyperbaric oxygen (HBO) therapy improved ischemic PAOD mainly through an increase of vascular wall permeability and recruiting endothelial progenitor cells (EPCs) to enhance the angiogenesis and blood flow in the ischemic area. Purpose This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors and blood flow in ischemic area in patients with peripheral arterial occlusive disease (PAOD). Methods 57 consecutive patients with PAOD undergoing the HBO therapy (3 atm for 2h/each time) were prospectively enrolled into the present study. The venous blood sampling was drawn for assessing the circulating levels of EPCs and soluble angiogenesis factors prior to and during five times of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow at ischemic area, was measured by moorVMS-PRES. Results The results demonstrated that the circulating levels of EPCs (CD34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors (VEGF/SDF-1α/HGF/FGF) were significantly increased in post-HBO therapy than in pre-HBO therapy (all p&lt;0.01). Additionally, Matrigel assay exhibited that the angiogenesis was significantly increased in post-HBO therapy than prior to the therapy (p&lt;0.001). Furthermore, the SPP was significantly increased in ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy than in pre-HBO therapy (all p&lt;0.01). Importantly, the HBO therapy did not show any complication and all the patients were uneventfully discharged without amputation. Conclusions HBO therapy augmented circulating levels of EPCs and angiogenesis factors as well as improved the blood flow in the ischemic area. Acknowledgement/Funding Kaohsiung Chang Gung Memorial Hospital, Taiwan Society of Stem Cell Research

Background Endothelial progenitor cells (EPC) and circulating endothelial cells (CEC) are cell populations mobilized from the bone marrow in response to endothelial damage. Its relationship with vascular risk damage and subclinical vascular damage in systemic lupus erythematosus (SLE) is being actively studied, but their role as an activity biomarker was not evaluated. Aim to study EPC and CEC levels in SLE patients and compare them to healthy controls, as well as study their relationship with clinical and analytical markers of disease activity. Methods A prospective, analytical, case-control study was conducted; in a center for systemic autoimmune diseases in Montevideo, Uruguay. EPCs and CEC levels were quantified by multiparametric flow cytometry. EPCs were defined as CD45low/-, CD34+, CD133+, CD31+, CD146+, CD3- and CEC as CD45low/-, CD34+, CD133-, CD31+, CD146+, CD3-. Disease activity was assessed using ‘Systemic Lupus Erythematosus Disease Activity Index’ (SLEDAI) and ‘Physician’s Global Assessment’ (PGA), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), complement (C3 and C4), double-stranded DNA (dsDNA) antibody levels and proteinuria. Results 28 controls and 22 SLE patients age and sex matched were enrolled. Patients median ages was 29.5±11.5 years and controls were 36±11.25 years, (p=0.28). Sex ratio (female/male) was 22/2 and 24/4 in patients and controls (p=0.68). SLE patients showed significantly lower levels of EPC (median 0.2202±0.4377 cells/µl vs 1.051±1.3849 cells/µl), p EPC levels correlated with proteinuria/creatininuria ratio (r=0.5386, p=0.0097) and with dsDNA level (r=0.5118, p=0.0211) in SLE patients. EPC level was higher in patients with significant proteinuria (median 0.58710±1.5086 cells/µl vs 0.11502±0.42442 cells/µl), p=0.0474 (figure 1); and in patients with increased dsDNA level (median 0.5871±1.2562 cells/µl vs 0.1150±0.3504 cells/µl), p=0.0249. No correlation was found with the levels of C3, C4, SLEDAI, as well as prednisone dose at the time of enumeration. Conclusions EPS and CEC levels correlate with disease activity in SLE, particularly with renal involvement. Currently, we are enrolling more patients in order to confirm these results, but we postulate that, in the future, EPC may be used as a biomarker of disease activity.

The progression of cancer is largely dependent on neoangiogenesis. Circulating endothelial progenitor cells (EPC) have the ability to form complete vascular structures in vitro and play a crucial role in tumor vasculogenesis. Emerging evidence suggests that surgical injury may induce the mobilization of EPC in animal models, and this might have a negative effect on the prognosis of cancer patients. We studied 20 patients (10 men, 65+/-13 years) undergoing laparotomy for surgical treatment of various forms of abdominal cancer, and 20 age- and sex-matched healthy control subjects. The number of circulating EPC, defined as CD34+/KDR+ cells identified among mononuclear cells isolated from peripheral venous blood, was determined preoperatively and at days 1 and 2 after surgery. Surgery induced a significant increase in circulating EPC levels at day 1 (from 278/mL, interquartile range 171-334, to 558/mL, interquartile range 423-841, p<0.001) and day 2 (709/mL, interquartile range 355-834, p<0.001)compared with baseline values. EPC levels did not change in control subjects. Seven subjects who underwent laparotomic surgery for non-neoplastic disease also showed an increase in EPC levels after surgery (p=0.009 and p=0.028 at day 1 and day 2, respectively). We conclude that patients undergoing elective laparotomic surgery for cancer demonstrate an increase in EPC post-operatively. The potential adverse effects of surgical stress-induced EPC mobilization on tumor and metastasis growth in cancer patients need to be addressed in future studies.

Context: Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown.Objective: We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels.Methods: Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP (76.2 ± 51.5 μg m−3) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n = 21), white blood cell (n = 24) and vascular endothelial growth factor (VEGF) (n = 16–19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests.Results: Circulating EPC levels were elevated 2 [108.29 (6.24–249.71) EPC mL−1; median (25th–75th percentiles), p = 0.052] and 20 h [106.86 (52.91–278.35) EPC mL−1, p = 0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00–84.83) and 50.16 (0.00–104.79) EPC mL−1]. VEGF and white blood cell (WBC) levels did not differ between exposures.Conclusions: Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute “endothelial injury” and/or a circulating EPC response to sympathetic nervous system activation.

Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis

According to WHO cardiovascular diseases (CVDs) are the first cause of death in the world: more people die annually from CVDs than from any other cause. Vascular endothelium plays a pivotal role in the onset and the progression of these pathologies and cardiovascular risk factors are frequently associated to the levels of endothelial progenitor cells (EPCs), bone marrow-derived circulating progenitors for the endothelial lineage. Since EPCs not only preserve vascular endothelium homeostasis, but directly participate to re-endothelization and neovascularization, these cells represent an emerging actor in vascular competence and thus a cell model of great interest. An unhealthy diet is one of the main cardiovascular risk factor; there is indeed a great interest in the potential protective effects of nutraceuticals,, food-derived compounds that exert beneficial effects on human and animal health. The characterization of the endothelial effects of different nutraceuticals may provide fresh insights into their potential role in CVDs prevention. Several studies have already showed the protective effects of natural antioxidants on EPCs levels and functionality; some examples are resveratrol, catechin and folic acid. Fermentation has recently shown interesting roles in cardiovascular prevention since this process created a new class of food, rich in bioactive compounds, the fermented food. Consumption of fermented legumes and cereals, but also fermented beverages (such as beer and wine) was found to protect endothelial function through lipid-lowering, anti-inflammatory and antioxidative mechanisms. Little is known about the effects of fermentation-derived nutraceuticals on EPCs and given the important role of this cardiovascular biomarker, further analysis in this field can improve CVDs prevention and treatment.

BackgroundPatients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown.MethodsWe measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls.ResultsPatients with DM had significantly lower circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and higher Log baPWV compared with controls (all P < 0.05). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all P < 0.05). The circulating levels of Log CD34/KDR+ EPC (r = -0.46, P < 0.001) and Log CD133/KDR+ EPC counts (r = -0.45, P < 0.001) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, P < 0.05) and negatively correlated with circulating levels of Log CD34/KDR+ EPC (r = -0.40, P < 0.001) and Log CD133/KDR+ EPC (r = -0.41, P < 0.001). Multivariate analysis revealed that HbA1c, Log CD34/KDR+ and Log CD133/KDR+ EPC counts were independent predictors of Log baPWV (P < 0.05).ConclusionsIn patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.