Endothelial Progenitor Cells In Patients Research Articles

Kinetics of circulating endothelial progenitor cells in patients undergoing carotid artery surgery.

AimEndothelial progenitor cells (EPCs) are primitive cells found in the bone marrow and peripheral blood (PB). In particular, the potential of EPCs to differentiate into mature endothelial cells remains of high interest for clinical applications such as bio-functionalized patches for autologous seeding after implantation. The objective of this study was to determine EPCs’ kinetics in patients undergoing carotid artery thromboendarterectomy (CTEA) and patch angioplasty.MethodsTwenty CTEA patients were included (15 male, mean age 76 years). PB samples were taken at 1 day preoperatively, and at 1, 3, and 5 days postoperatively. Flow cytometric analysis was performed for CD34, CD133, KDR, and CD45. Expression of KDR, SDF-1α, and G-CSF was analyzed by means of enzyme-linked immunosorbent assay.ResultsFluorescence-activated cell sorting analysis revealed 0.031%±0.016% (% of PB mononuclear cells) KDR+ cells and 0.052%±0.022% CD45−/CD34+/CD133+ cells, preoperatively. A 33% decrease of CD45−/CD34+/CD133+ cells was observed at day 1 after surgery. However, a relative number (compared to initial preoperative values) of CD45−/CD34+/CD133+ cells was found on day 3 (82%) and on day 5 (94%) postoperatively. More profound upregulated levels of CD45−CD34+/CD133+ cells were observed for diabetic (+47% compared to nondiabetic) and male (+38% compared to female) patients. No significant postoperative time-dependent differences were found in numbers of KDR+ cells and the concentrations of the cytokines KDR and G-CSF. However, the SDF-1α levels decreased significantly on day 1 postoperatively but returned to preoperative levels by day 3.ConclusionCTEA results in short-term downregulation of circulating EPCs and SDF-1α levels. Rapid return to baseline levels might indicate participation of EPCs in repair mechanisms following vascular injury.

Number and function of circulating endothelial progenitor cells in patients with primary Budd-Chiari syndrome

Primary Budd-Chiari syndrome (BCS) is associated with vascular endothelial injury. Circulating endothelial progenitor cells (EPCs) provide an endogenous mechanism to repair endothelial injury. This study investigated the levels and functionality of EPCs in patients with primary BCS. EPCs (CD34+/CD133+/KDR+) were quantified in 82 patients with primary BCS (inferior vena cava type: n=19; hepatic vein type: n=22; and mixed type: n=41), 10 cirrhosis controls (CC group) and 10 age-matched healthy controls (HC group), using flow cytometry. EPCs proliferation was detected by MTT assay, adhesion by adhesion activity assay, and migration capacity by Transwell assay. EPCs levels were significantly lower in the BCS group (0.020±0.005%) than in the CC and HC groups (0.260±0.201%, 0.038±0.007%; P<0.001 for each). EPCs cultured in vitro from BCS and CC groups had, respectively, lower proliferation activity (0.20±0.04, 0.23±0.06 vs 0.58±0.07, each P<0.001), adhesion activity (15.8±1.7, 18.2±4.3 vs 35.0±2.5 cells/random microscopic field (RMF), each P<0.001) and migration activity (16.1±1.5, 16.7±3.0 vs 23.9±2.0 cells/RMF, each P<0.001) than in the HC group. EPCs functionality did not significantly differ between the BCS and CC groups. The numbers and functions of EPCs did not significantly differ among patients with inferior vena cava type, hepatic vein type and mixed type of BCS. Patients with primary BCS had lower EPCs levels, with less proliferation, adhesion and migration activities. These findings suggest that lower levels of less functional EPCs may be associated with venous occlusion in primary BCS patients.

Endothelial Dysfunction in Idiopathic Sudden Sensorineural Hearing Loss: A Review.

An endothelial dysfunction has been described in idiopathic sudden sensorineural hearing loss (ISSHL) patients. The purpose of our review was to: i) identify, evaluate and review recent research about cardiovascular risk factors involvement and signs of endothelial dysfunction in ISSHL; ii) implication of these discovering in clinical practice and future research. A Medline literature search was conducted to identify any study on the involvement of endothelial dysfunction in ISSHL, published in the English language in the last decade. The following MEDLINE search terms were used: sudden sensorineural hearing loss (SSHL) and endothelial dysfunction (text words). Additional studies were identified by hand searching the references of original articles and review articles. Studies were not excluded on the basis of the qualitative or quantitative definitions of SSHL, treatment regimens, or outcome measures. Data were extracted from included papers by a reviewer. Information on the patients, investigations, methods, interventions, and outcomes were systematically analyzed. Characteristics and results of all included studies were reviewed systematically. High levels of adhesion molecules, hyperhomocysteinemia and lower folate levels, unbalanced oxidative status, a lower value of flow-mediated dilatation of brachial artery and a reduced percentage of circulating endothelial progenitor cells in patients affected by ISSHL support the hypothesis that this syndrome should be considered as a microcirculation disorder based on endothelial dysfunction and drive clinicians to implement all the traditional strategies used for preventing cardiovascular events, to also reduce the likelihood of ISSHL occurrence.

Abstract 40: Interleukin-10 Deficiency Impairs Reparative Properties of Bone Marrow-derived Endothelial Progenitor Cell Exosomes Function in Ischemic Myocardium

Endothelial progenitor cell (EPC) based therapy promotes neovascularization in ischemic myocardium. Studies suggest that therapeutic effect of stem cells is largely due to paracrine mechanisms including stem cell-derived exosomes that are emerging as key paracrine mediators of stem cell functions. However, the autologous transplantation of EPCs in patients with systemic inflammation, which is a common symptom in patients with ischemic heart diseases, yield modest results suggesting the compromised cell function and altered exosome performance. We hypothesized that EPCs under inflammatory stress secrete dysfunctional exosomes with altered contents including packaged microRNAs, which eventually compromises exosomes repair ability in ischemic myocardium. Whether modulation of identified targets like specific microRNAs in the cargo of exosomes can rescue and/or enhance their reparative properties of dysfunctional exosomes is not known. We have previously shown in Interleukin-10 (IL-10) KO mice (model mimicking systemic inflammation) that loss of IL-10 impairs EPCs functions via miR-375. After cell expansion, we isolated exosomes from these two groups and compared their functions in terms of cell survival, proliferation, migration and angiogenic capacity in vitro and in vivo . We report that WT-EPC-exosomes (Exo) transplantation in the ischemic myocardium after MI significantly improved post-infarct repair, neovascularization and left ventricle functions. Our in vitro studies revealed that WT-EPC-Exo treatment enhanced endothelial cells proliferation and tube formation and inhibited apoptosis; whereas IL-10 KO-EPC-Exo exhibited opposite effects, suggesting that reparative capacity of WT-EPC-Exo is lost in exosomes derived from IL-10 KO-EPCs. Exosome miRNA profiling revealed a drastically different expression patterns with enrichment of inflammation induced microRNAs including significantly higher expression of miR-375. Interestingly, Knockdown of miR-375 in IL-10-EPCs decreased the expression level of miR-375 in their exosomes and partly rescued their angiogenic dysfunctions. Taken together, our studies suggest that modulation of miR-375 in IL-10 KO-EPC-Exo can rescue its phenotype and promote cardiac repair.

Circulating endothelial cells and their progenitors in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management.

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.

219 Quantification, culture and characterization of circulating endothelial progenitor cells in patients with renal cell carcinoma

219 Quantification, culture and characterization of circulating endothelial progenitor cells in patients with renal cell carcinoma

Testosterone modulates endothelial progenitor cells in rat corpus cavernosum.

To investigate the effects of testosterone on cavernosal endothelial progenitor cells (EPCs) in a castrated rat model. In all, 45 male Sprague-Dawley rats (12-weeks old) were divided into control, surgical castration, and castration with testosterone replacement groups. The rats were castrated under ketamine anaesthesia, and testosterone was administered by daily subcutaneous injection of 3 mg/kg testosterone propionate. The corpus cavernosum was obtained after perfusion with 10 mL saline via the abdominal aorta 4 weeks later. The expression of EPC-specific markers [cluster of differentiation 34 (CD34), fetal liver kinase 1 (Flk1), and vascular endothelial (VE)-cadherin] was evaluated by flow cytometry analysis and immunofluorescence staining. CD34+/Flk1+ and CD34+/VE-cadherin+ cells were detected in the cavernosal sinusoidal endothelial space. Flow cytometry analysis showed that CD34 and Flk1 double positive cells (EPCs) comprised ≈3.79% of the corpus cavernosum in normal rats. The percentage of EPC marker-positive cells decreased significantly in the castration group (2.8%; P < 0.05) and was restored to 3.56% after testosterone supplementation. Confocal microscopy revealed that the numbers of CD34+/Flk1+ and CD34+/VE-cadherin+ cells decreased in castrated rats compared with controls, but were similar to control levels in rats receiving testosterone replacement. The EPC markers were expressed in the cavernosal sinusoidal endothelial space, and the numbers of resident EPCs were regulated by testosterone. These results suggest that testosterone replacement therapy may improve erectile function by modulating EPCs in patients with hypogonadism.

Phase 1–2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow–derived endothelial progenitor cells

The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for exvivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P0.042) in the first 90days after cells administration and 5 of the 9 patients alive at 90days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation.

Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review.

Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85%) and improved organ function in 12 studies (92%). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies. Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.

Vistafin as an Independent Predictor for Declined Numerous of Non-Classical Endothelial Progenitor Cells in Patients with Type 2 Diabetes Mellitus

Vistafin as an Independent Predictor for Declined Numerous of Non-Classical Endothelial Progenitor Cells in Patients with Type 2 Diabetes Mellitus

Endothelial progenitor cells as markers of severity in hypertrophic cardiomyopathy.

Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are mobilized into the circulation to migrate and differentiate into mature endothelial cells contributing to post-natal physiological and pathological neovascularization. In this study, we evaluated circulating EPCs in patients with hypertrophic cardiomyopathy (HCM) and examined a potential association with clinical parameters of the disease. We included 40 HCM patients and 23 healthy individuals. Using flow cytometry we measured EPCs in peripheral blood as two subpopulations of CD45-/CD34+/VEGFR2+ and CD45-/CD34+/CD133+ cells. Circulating CD45-/CD34+/VEGFR2+ cells were significantly increased in HCM patients in comparison with the controls (0.000238 ± 0.0003136 vs. 0.000057 ± 0.0001316, respectively, P = 0.002). However, there was no significant difference in the number of circulating CD45-/CD34+/CD133+ cells (0.003079 ± 0.0033288 vs. 0.002065 ± 0.0022173, respectively, P = 0.153). The CD45-/CD34+/VEGFR2+ subpopulation revealed a moderate correlation with LV mass index (r = 0.35, P = 0.026), while both EPC subpopulation levels showed strong positive correlations with th E/e' ratio (r = 0.423, P = 0.007 for CD45-/CD34+/VEGFR2+ and r = 0.572, P < 0.001 for CD45-/CD34+/CD133+). HCM patients showed an increased mobilization of EPCs compared with healthy individuals that correlated with diastolic dysfunction. Our findings may open up new dimensions in the pathophysiology, prognostication, and treatment of HCM.

Effect of High-Dose Atorvastatin Reload on the Release of Endothelial Progenitor Cells in Patients on Long-Term Statin Treatment Who Underwent Percutaneous Coronary Intervention (from the ARMYDA-EPC Study)

Endothelial progenitor cells (EPCs) may concur to endogenous vascular repair. Previous studies have reported that statin treatment increases EPC levels. We investigated whether this occurs in patients on long-term statin treatment who underwent percutaneous coronary interventions (PCIs). In a phase A study, 53 patients (atorvastatin reload [AR] 80 mg 12 hours before + 40 mg 2 hours before PCI, n = 27; placebo [P], n = 26) were evaluated for EPC mobilization as CD45dim/CD34+/CD133+/KDR+ cell number by flow cytometry. Assays were run at randomization (12 hours before PCI, R), immediately before PCI (T0) at 8 (T8) and 24 hours (T24). In phase B study, 50 patients (AR, n = 25; P, n = 25) were evaluated for early colony formation by Hill colony forming unit (CFU) assay, with sampling at randomization and 24 hours later. In phase A, EPCs levels were similar at randomization between 2 arms (0.23% [0.14 to 0.54] of total events in AR vs 0.22% [0.04 to 0.37] in P group; p = 0.33). At PCI, EPC levels were higher in AR arm (0.42% [0.06 to 0.30] vs 0.19% [0.06 to 030]; p = 0.009). Higher EPC levels in AR group were also found at 8 and 24 hours. In phase B, EPC CFUs/well numbers at randomization were similar in the 2 arms (8 [6 to 12] in AR vs 12 [6 to 20] in P group, p = 0.109). EPC CFU/well at 24 hours became significantly higher in AR arm (17 [10 to 23] vs 5 [2 to 13], p = 0.002). In conclusion, high-dose AR before PCI in patients on long-term statin therapy promptly increases EPCs mobilization, which are capable of early colony formation and may contribute to cardioprotection.

Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia.

Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells. Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months. In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = −0.266; p < 0.01) (EPC: r = −0.297; p < 0.001)], CRP (TEM: r = −0.283; p < 0.01) (EPC: r = −0.260; p < 0.01). We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.

Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction.

This study evaluated the effects of electroacupuncture (EA) on endothelial function and endothelial progenitor cells (EPC) in patients with cerebral infarction. In a randomized, placebo-controlled, crossover study, 20 patients with cerebral infarction were randomized into two treatment groups: EA or placebo. Before and after each intervention, pulse amplitude tonometry (PAT) was used to assess endothelial function and peripheral blood was analyzed for the number of EPCs. Circulating EPCs were quantified by flow cytometry as CD45(low) CD34(+) KDR2(+) cells. Plasma vascular endothelial growth factor (VEGF) and interleukin (IL)-10 levels were measured. Seven days later, crossover was performed on each group, with each group receiving the other treatment using the same protocol. The PAT hyperemia ratio ranged from 1.57 ± 0.41 to 2.04 ± 0.51 after EA, representing a significant improvement (P = 0.002); however, there was no improvement in the placebo group (P = 0.48). Circulating EPCs, as measured by flow cytometry, increased to 110.6 ± 74.3/100 μL in the EA group (P = 0.001) but did not change in the placebo group (45.9 ± 35.3/100 μL, P = 0.08). The increases in the number of EPCs and the PAT ratio after treatment were correlated (r = 0.78, P < 0.001). Plasma VEGF levels increased with EA compared to baseline (261.2 ± 34.0 vs 334.9 ± 80.5 pg/mL, P = 0.003). The number of circulating EPCs was positively correlated with plasma levels of VEGF (r = 0.50, P = 0.02). In conclusion, EA induced improvement of EPC levels and the PAT ratio in patients with cerebral infarction.

Altered circulating endothelial progenitor cells in patients with keloid.

Evidence has suggested that vascular endothelial growth factor (VEGF), a crucial growth factor in regulating endothelial progenitor cells (EPCs), plays a central role in keloid formation. However, the levels of circulating EPCs in patients with keloid have not yet been explored. The aim of this study was to determine the number of circulating EPCs in patients with keloid. Circulating EPCs (defined as CD45- CD34+CD133+VEGFR2+cells) and VEGF levels from 39 patients with keloid and 22 healthy controls (HCs) were assessed by flow cytometry and ELISA, respectively. EPCs were detectable in the peripheral blood of patients with keloid. The number of circulating EPCs and the levels of plasma VEGF were significantly higher in patients with keloid than in HCs. However, no correlation was found between the number of circulating EPCs and the serum VEGF levels. This study provides the first evidence that EPCs are increased in the peripheral blood of patients with keloid. Understanding the roles of EPCs in keloid fromation may lead to the development of novel therapeutic strategies for keloid.

Exercise-induced mobilisation of endothelial progenitor cells in patients with premature coronary heart disease.

Endothelial progenitor cells (EPC) derive from bone marrow and participate in both endothelial regeneration and development of new blood vessels. EPC also play a role in the atherosclerotic process, and their number correlates negatively with the presence of classical risk factors. To evaluate circulating EPC count and their exercise-induced mobilisation in patients with premature coronary artery disease (CAD). The study group included 60 patients with stable CAD diagnosed before 45 years of age. The control group consisted of 33 healthy age- and gender-matched volunteers. Venous blood was sampled 3 times in order to assess circulating EPC count immediately before an exercise test (EPC 0) and at 15 min (EPC 15) and 60 min (EPC 60) after the exercise test. Circulating EPC count in the study group at rest and at 15 min after exercise was comparable (2.1 vs. 2.1 cell/μL, p = 0.35) and increased significantly at 60 min after exercise in comparison to resting values (2.1 vs. 3.2 cell/μL, p < 0.00001). In the control group, circulating EPC count increased significantly at 15 min after exercise (2.0 vs. 3.5 cell/μL, p < 0.0001) but later decreased at 60 min after exercise, although it remained greater than at rest (2.7 vs. 2.0 cell/μL, p < 0.0002). Circulating EPC count at rest and at 60 min after exercise was comparable in the two groups (2.1 vs. 2.0 cell/μL, p = 0.96; and 3.2 vs. 2.7 cell/μL, p = 0.13, respectively) but it was significantly lower in the study group compared to the control group at 15 min after exercise (2.1 vs. 3.5 cell/μL, p < 0.00001). Circulating EPC count at rest and at 15 min after exercise did not correlate with the number of stenosed coronary arteries but at 60 min after exercise it was greater in patients with one-vessel disease compared to those with two- or three-vessel disease (4.2 vs. 3.4 cell/μL, p = 0.01; and 4.2 vs. 2.3 cell/μL, p = 0.00003). However, no difference in circulating EPC count was seen at 60 min after exercise between patients with two- or three-vessel disease (3.4 vs. 2.3 cell/μL, p = 0.3). 1. Circulating EPC count at rest is comparable between subjects with premature atherosclerosis and healthy volunteers. 2. A single bout of physical exercise causes a significant increase in circulating EPC count in both groups, but the dynamics of exercise-induced EPC mobilisation is different, with delayed exercise-induced EPC mobilisation in subjects with premature CAD. 3. The extent of atherosclerotic coronary lesions does not influence circulating EPC count at rest.

Endothelial dysfunction in ankylosing spondylitis associated with reduced endothelial progenitor cell population

Background: Endothelial dysfunction, and cardiovascular (CV) morbidity and mortality have been documented in patients with ankylosing spondylitis (AS). Endothelial progenitor cells (EPCs) have reparative potential in overcoming the endothelial dysfunction and reducing cardiovascular risk. Aim: To investigate the relationship between endothelial function and EPCs in patients with AS in a cross-sectional study. Methods: Circulating EPCs (CD34+/CD133+) were isolated and quantified from peripheral blood samples of AS (n23) and healthy controls (n=20) matched for age and sex. Endothelium-depended vascular function, i.e. flow-mediated dilation (FMD), was assessed for all subjects. Disease activity was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored using Bath Ankylosing Spondylitis Functional Index (BASFI). All subjects were free of any other known traditional CV risk factors. Results: AS patients had depleted level of circulating %EPCs (0.028 ± 0.001% versus 0.045 ± 0.011%, P <0.001) and reduced FMD% (6.77 ± 2.15 versus 10.06 ± 0.55, P <0.001) than healthy controls. Circulating EPC population significantly positively correlated with FMD% (r 0.538, P = 0.008). Levels of CD34+/CD133+ putative cells showed a significant inverse correlation with disease duration (P = 0.01), BASDAI (P = 0.04), ESR (P = 0.002) and CRP (P = 0.007). Conclusion: AS patients, free of any other known CV risk factors, demonstrated depleted levels of EPCs and reduced endothelial function. These alterations may cause further deterioration of endothelial function in AS patients. EPC would possibly serve as a novel therapeutic target for preventing cardiovascular risk in AS.

Effects of Electroacupuncture on Endothelial Function and Circulating Endothelial Progenitor Cells in Patients with Cerebral Infarction

Effects of Electroacupuncture on Endothelial Function and Circulating Endothelial Progenitor Cells in Patients with Cerebral Infarction

Influence of depression and anxiety on circulating endothelial progenitor cells in patients with acute coronary syndromes.

Circulating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS). Patients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID-I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM-IV criteria. The EPCs were defined as CD133(+) CD34(+) KDR(+) and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate. Out of 111 ACS patients, 57 were found to have a DSM-IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode. The current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders.