Endothelial Progenitor Cells Counts Research Articles

PU.1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung-homing through Wnt/β-catenin and CXCL12/CXCR4 pathways.

Endothelial progenitor cells (EPCs) dysfunction is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The transcription factor PU.1 is essential for the maintenance of stem/progenitor cell homeostasis. However, the role of PU.1 in COPD and its effects on EPC function and lung-homing, remain unclear. This study aimed to explore the protective activity of PU.1 and the underlying mechanisms in a cigarette smoke extract (CSE)-induced emphysema mouse model. C57BL/6 mice were treated with CSE to establish a murine emphysema model and injected with overexpressed PU.1 or negative control adeno-associated virus. Morphometry of lung slides, lung function, and apoptosis of lung tissues were evaluated. Immunofluorescence co-localization was used to analyze EPCs homing into the lung. Flow cytometry was performed to detect EPC count in lung tissues and bone marrow (BM). The angiogenic ability of BM-derived EPCs cultured in vitro was examined by tube formation assay. We determined the expression levels of PU.1, β-catenin, C-X-C motif ligand 12 (CXCL12), C-X-C motif receptor 4 (CXCR4), stem cell antigen-1 (Sca-1), and stemness genes. CSE exposure significantly reduced the expression of PU.1 in mouse lung tissues, BM, and BM-derived EPCs. PU.1 overexpression attenuated CSE-induced emphysematous changes, lung function decline, and apoptosis. In emphysematous mice, PU.1 overexpression markedly reversed the decreased proportion of EPCs in BM and promoted the lung-homing of EPCs. The impaired angiogenic ability of BM-derived EPCs induced by CSE could be restored by the overexpression of PU.1. In addition, PU.1 upregulation evidently reversed the decreased expression of β-catenin, CXCL12, CXCR4, Scal-1, and stemness genes in mouse lung tissues, BM, and BM-derived EPCs after CSE exposure. PU.1 alleviates the inhibitory effects of CSE on EPC function and lung-homing via activating the canonical Wnt/β-catenin pathway and CXCL12/CXCR4 axis. While further research is needed, our research may indicate a potential therapeutic target for COPD patients.

The Impact of Modern Anti-Diabetic Treatment on Endothelial Progenitor Cells.

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel's intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin.

Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

Detection of Angiogenic T Cells and Endothelial Progenitor Cells in Behçet Disease and Determination of Their Relationship with Disease Activity.

Angiogenic T (Tang) cells and endothelial progenitor cells (EPCs) play a role in maintaining vascular integrity and repair. This study considers the association between them and Behçet disease (BD) and disease activity. Fifty patients with BD and forty-five age- and gender-matched healthy controls were included in the study. The participants' demographic, clinical, and laboratory characteristics were recorded, and their blood Tang cell and EPC counts were determined. Fifty patients were diagnosed with BD, consisting of 24 females and 26 males. The blood Tang cell (3.5 ± 1.2 cells/μL in patients, 4 ± 0.9 cells/μL in controls, p = 0.046)) and EPC (2.9 ± 0.9 cells/μL in patients, 3.7 ± 1 cells/μL in controls, p = 0.001) counts were significantly lower for the patient group with BD than for the control group. The blood Tang cell (42.5 ± 4.9% in active patients, 48.9 ± 7.9% in inactive patients, p = 0.001) and EPC (35.5 ± 6.4% in active patients, 41.2 ± 6.3% in inactive patients, p = 0.004) levels were lower for the patient group with active BD than for the inactive patient group. A weak positive correlation was present between the blood Tang cell and EPC percentage values in BD (r: 0.318, p = 0.002). It was determined that Tang cell and EPC counts are lower in BD, and these reductions become more profound with increasing disease activity. This situation may prevent the development of a sufficient immune response against a disease with a course of chronic inflammation or may trigger the formation of autoreactive immunity. A reduction in Tang cells and EPCs may serve as a marker or predictor of vascular damage in BD patients and represents the progression of vascular injury.

Evaluation of Endothelial Progenitor Cell Characteristics as Clinical Biomarkers for Elderly Patients with Ischaemic Stroke.

Ageing impairs endothelial function and predisposes the person to ischaemic stroke (IS). Endothelial progenitor cells (EPCs) repair endothelial damage and induce post-ischaemic neovascularisation. Given the prevalence of IS in older population, this study explored whether changes in EPC number and function may reliably predict the type or outcome of stroke in patients ≥ 65years of age. For this, blood samples were collected once from healthy volunteers (HVs, n = 40) and four times (admission and days 7, 30 and 90 post-stroke) from participants with lacunar (n = 38) or cortical (n = 43) stroke. EPCs were counted with flow cytometry and defined as non-haematopoietic cells (CD45-) expressing markers for stemness (CD34 +), immaturity (CD133 +) and endothelial maturity (KDR +). Clonogenesis, tubulogenesis, migration and proliferation assays were performed as measures of EPC functionality. Biochemical profile of plasma inflammatory and angiogenic agents were studied using specific ELISAs. Primary outcome was disability or dependence on day 90 post-stroke, assessed by the modified Rankin Scale (mRS). Compared to HVs, EPC numbers were higher in stroke patients at all time points studied, reaching significance at baseline and day 30. No differences in EPC counts and functionality were observed between lacunar and cortical stroke groups at any time. Plasma endostatin, PDGF-BB, TNF-α and VEGF levels were higher in stroke patients vs HVs. Patient outcome, evaluated by mRS on day 90 post-stroke, did not correlate with EPC count or functionality. Baseline EPC counts may serve as a diagnostic marker for stroke but fail to distinguish between different stroke subtypes and predict post-stroke outcome.

Royal Jelly Increases Hematopoietic Stem Cells in Peripheral Blood: A Double-Blind, Placebo-Controlled, Randomized Trial in Healthy Subjects.

Royal jelly (RJ), produced by honeybees, influences stem cell functions, such as pluripotency maintenance of mouse embryonic stem cells and prevention of aging-related muscle stem cell functional deterioration. Thus, we hypothesized that RJ administration has various health-promoting effects based on stem cells. However, its effects are unknown in humans. In this study, we have attempted for the first time to clarify whether the administration of RJ in humans affects stem cells. This randomized, double-blind, placebo-controlled study was performed on healthy subjects (n = 90) who received protease-treated RJ at a dose of 1200 mg/day or placebo daily for four weeks. Also, the participants with a low number of hematopoietic stem cells (HSCs) in peripheral blood were preferentially selected. HSC counts, endothelial progenitor cell (EPC) counts, blood cell counts in peripheral blood, cytokines in serum, and physical conditions were evaluated. Results and Conclusion. Eligible data from 86 subjects (placebo: 42, RJ: 44) who completed the study were analyzed. There were no significant differences between the two groups regarding the changes in peripheral HSC count (p=0.103), while diastolic blood pressure showed a significant improvement in the RJ group compared to that in the placebo group (p=0.032). The subgroup analysis excluded 14 subjects who complained of cold symptoms at baseline or within five days of the four-week study. The changes in the HSC populations were significantly higher in the RJ group than those in the placebo group (p=0.042). No adverse effects were observed in any of the groups. These results suggest that RJ administration affected the peripheral HSC count and may influence stem cell functions. Further research is needed to reveal the various health-promoting benefits of RJ based on stem cells.

Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.

Spinal muscular atrophy (SMA) is a neuromuscular disorder due to degeneration of spinal cord motor neurons caused by deficiency of the ubiquitously expressed SMN protein. Here, we present a retinal vascular defect in patients, recapitulated in SMA transgenic mice, driven by failure of angiogenesis and maturation of blood vessels. Importantly, the retinal vascular phenotype was rescued by early, systemic SMN restoration therapy in SMA mice. We also demonstrate in patients an unfavorable imbalance between endothelial injury and repair, as indicated by increased circulating endothelial cell counts and decreased endothelial progenitor cell counts in blood circulation. The cellular markers of endothelial injury were associated with disease severity and improved following SMN restoration treatment in cultured endothelial cells from patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarker findings indicate microvasculopathy as a fundamental feature of SMA. Our findings provide mechanistic insights into previously described SMA microvascular complications, and highlight the functional role of SMN in the periphery, including the vascular system, where deficiency of SMN can be addressed by systemic SMN-restoring treatment.

Thrombin generation and endothelial progenitor cell function among patients with acute myocardial infarction treated with prasugrel versus ticagrelor

Abstract Objectives To compare the effects of prasugrel and ticagrelor on thrombin generation (TG) and circulating endothelial progenitor cells (EPCs) in the acute phase of ST-segment elevation myocardial infarction (STEMI). Background TG, platelet function and EPCs have an important role in the pathophysiology of coronary artery disease (CAD). To date, the effect of novel P2Y12 inhibitors on these coagulation mediators has only been studied in the sub-acute phase following acute myocardial infarction. Methods Patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either ticagrelor or prasugrel treatment. TG, platelet reactivity and EPC were tested prior to P2Y12 inhibitor loading dose (T0), and 24 hours following PPCI (T1). Results Between December 2018 and July 2021, 83 consecutive STEMI patients were randomized to ticagrelor (N=42) or prasugrel (N=41) treatment. No differences were observed at T0 for all measurements. At T1, prasugrel was found to be a more potent TG inhibitor: lower thrombin peak levels (319.5±237.7 nmol/L vs. 433.5±264.3 nmol/L, p=0.06), longer time to peak (14.1±12.6 min vs. 8.3±9.7 min, p=0.03), longer lag time to TG initiation (7.7±7.5 min vs. 3.9±2.1 min, p&amp;lt;0.01) and a smaller AUC (2186.1±1123.1 vs. 3362.5±2108.5, p&amp;lt;0.01). Furthermore, levels of CD34 (2.6±4.1 vs. 1.1±1.1, p=0.01), CD133 (2.3±1.8 vs. 1.4±1.5, p=0.01) and CFUs (2.1±1.5 vs. 1.1±1.0, p&amp;lt;0.01) were significantly higher in the prasugrel group, as compared to the ticagrelor group. Conclusion Among STEMI patients treated with PPCI, treatment with prasugrel as compared to ticagrelor was associated with more potent inhibition of TG and improved EPCs count and function. Funding Acknowledgement Type of funding sources: None.

IL-10 promotes endothelial progenitor cell infiltration and wound healing via STAT3.

Endothelial progenitor cells (EPCs) contribute tode novoangiogenesis, tissue regeneration, and remodeling. Interleukin 10 (IL-10), an anti-inflammatory cytokine that primarily signals via STAT3, has been shown to drive EPC recruitment to injured tissues. Our previous work demonstrated that overexpression of IL-10 in dermal wounds promotes regenerative tissue repair via STAT3-dependent regulation of fibroblast-specific hyaluronan synthesis. However, IL-10's role and specific mode of action on EPC recruitment, particularly in dermal wound healing and neovascularization in both normal and diabetic wounds, remain to be defined.Therefore, inducible skin-specific STAT3knockdown mice were studied to determine IL-10's impact on EPCs, dermal wound neovascularization and healing, and whether it is STAT3-dependent. We show that IL-10 overexpression significantly elevated EPC counts in the granulating wound bed, which was associated with robust capillary lumen density and enhanced re-epithelialization of both control and diabetic (db/db) wounds at day 7. We noted increased VEGF and high C-X-C motif chemokine 12 (CXCL12) levels in wounds and a favorable CXCL12gradient at day 3 that may support EPC mobilization and infiltration from bone marrow to wounds, an effect that was abrogated in STAT3knockdown wounds. These findings were supportedin vitro. IL-10 promoted VEGF and CXCL12synthesis in primary murine dermal fibroblasts, with blunted VEGF expression upon blocking CXCL12 in the media by antibody binding. IL-10-conditioned fibroblast media also significantly promoted endothelial sprouting and network formation. In conclusion, these studies demonstrate that overexpression of IL-10 in dermal wounds recruits EPCs and leads to increased vascular structures and faster re-epithelialization.

Circulating endothelial cells and endothelial progenitor cells as potential predictors of acute GVHD after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) is a major cause of treatment-related mortality after allogeneic hematopoietic stem cell transplantation. Endothelial cell damage may trigger the initiation of aGVHD. Endothelial damage and repair were evaluated by counting circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in 17 allogeneic hematopoietic stem cell transplantation patients at pre-conditioning, day 0, day 7, day 14, day 30, and day 60 by multicolor flow cytometry. Von Willebrand factor activity was simultaneously measured. Eight patients developed aGVHD and were compared to non-aGVHD patients. Patients' characteristics were not different, except for previous treatment courses. There was no difference in von Willebrand factor activity between the two groups. Both CEC and EPC counts were decreased on day 7 and day 14 and then increased thereafter. The CEC count on day 7 was significantly lower in the aGVHD group than in the non-aGVHD group (p=.0401). Restoration of the EPC count on day 60 was significantly suppressed in the aGVHD group (p=.0464). The CEC count on day 7 could predict aGVHD development (AUC 0.8214, p=.0372). The present results showed that CEC count on day 7 could be a predictor of aGVHD.

The Potential Mechanism Behind Native and Therapeutic Collaterals in Moyamoya

Background and PurposeTo explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD).MethodsAn angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated.ResultsEighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group.ConclusionsThese data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.

Multi-Omics Signatures Link to Ticagrelor Effects on Vascular Function in Patients With Acute Coronary Syndrome.

Long-term antiplatelet agents including the potent P2Y12 antagonist ticagrelor are indicated in patients with a previous history of acute coronary syndrome. We sought to compare the effect of ticagrelor with that of aspirin monotherapy on vascular endothelial function in patients with prior acute coronary syndrome. This was a prospective, single center, parallel group, investigator-blinded randomized controlled trial. We randomized 200 patients on long-term aspirin monotherapy with prior acute coronary syndrome in a 1:1 fashion to receive ticagrelor 60 mg BD (n=100) or aspirin 100 mg OD (n=100). The primary end point was change from baseline in brachial artery flow-mediated dilation at 12 weeks. Secondary end points were changes to platelet activation marker (CD41_62p) and endothelial progenitor cell (CD34/133) count measured by flow cytometry, plasma level of adenosine, IL-6 (interleukin-6) and EGF (epidermal growth factor), and multi-omics profiling at 12 weeks. After 12 weeks, brachial flow-mediated dilation was significantly increased in the ticagrelor group compared with the aspirin group (ticagrelor: 3.48±3.48% versus aspirin: -1.26±2.85%, treatment effect 4.73 [95% CI, 3.85-5.62], P<0.001). Nevertheless ticagrelor treatment for 12 weeks had no significant effect on platelet activation markers, circulating endothelial progenitor cell count or plasma level of adenosine, IL-6, and EGF (all P>0.05). Multi-omics pathway assessment revealed that changes in the metabolism and biosynthesis of amino acids (cysteine and methionine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis) and phospholipids (glycerophosphoethanolamines and glycerophosphoserines) were associated with improved brachial artery flow-mediated dilation in the ticagrelor group. In patients with prior acute coronary syndrome, ticagrelor 60 mg BD monotherapy significantly improved brachial flow-mediated dilation compared with aspirin monotherapy and was associated with significant changes in metabolomic and lipidomic signatures. URL: https://www. gov; Unique identifier: NCT03881943.

Endothelial Progenitor Cells in Coronary Atherosclerosis and Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

IntroductionThe role of endothelial progenitor cells (EPCs) in atherosclerosis progression and neointimal growth after percutaneous coronary intervention (PCI) remains controversial. The purpose of this study was to perform a systematic review and meta-analysis of studies on EPCs in patients who had PCI. MethodsWe searched Pubmed, Embase and Cochrane databases and reviewed cited references up to August 31, 2021. Overall, we selected 9 studies, including 4612 patients. ResultsLower baseline EPC count was associated with a significantly greater occurrence of in-stent restenosis (HR 1.33; 95% CI 0.97–1.82, P = 0.045). As for EPC coating, there was no significant difference in the 1-year occurrence of cardiac death between EPCs-capturing drug-eluting stents (DES) and standard DES (Relative Risk [RR] 1.146; 95% CI 0.666–1.974, P = 0.98), but target lesion revascularization (RR 1.727; 95% CI: 1.199–2.487, P = 0.025), and target vessel failure (RR 1.591; 95% CI 1.213–2.088, P = 0.04) were significantly more common with EPCs-capturing DES than with standard DES. ConclusionCirculating EPC count might improve risk stratification after PCI, as it is correlated with the occurrence of in-stent restenosis. Currently available EPCs-capturing DES use was associated with an increased risk of 1-year adverse events, mainly driven by an increase in target lesion revascularization and target vessel failure, not cardiac death.

Endothelial Progenitor Cells Count after Acute Ischemic Stroke Predicts Functional Outcome in Patients with Carotid Atherosclerosis

ObjectivesCirculating Endothelial Progenitor Cells (EPCs) predict cardiovascular outcomes in patients with coronary disease. However, the predictive value of EPCs after ischemic stroke is not well established. We aimed to study the prognostic role of EPCs in patients with acute ischemic stroke and carotid atherosclerosis, focusing on post-stroke functional outcome and stroke recurrences. Materials and MethodsWe studied consecutive adult patients with an acute (<7 days) anterior circulation ischemic stroke and carotid atherosclerosis. Cardioembolic strokes were excluded. We measured circulating EPCs by flow cytometry (CD34+/CD133+/KDR+) at inclusion (7±1 days after stroke) and at one year of follow-up. At three months and at one year we registered the modified Rankin Scale score, stroke recurrences and coronary syndromes during the follow-up. ResultsWe studied 80 patients with a mean age of 74.3±10.4 years. We divided the population in tertiles according to the EPCs count. At three months we observed a favorable outcome in 25/36 (69.4%) patients in the lowest, 19/22 (86.4%) in the medium and 21/22 (95.5%) in the highest tercile (p=0.037). In the multivariable analysis a higher EPCs count was associated with favorable functional outcome after adjusting for age and baseline NIHSS score (OR=3.61, 95%CI 1.34-9.76; p=0.011). This association persisted at one year of follow-up. We did not find association between counts of EPCs and stroke recurrence. ConclusionsIn patients with acute ischemic stroke and carotid atherosclerosis, a higher count of EPCs was associated with favorable functional outcome in the mid and long-term follow-up. Counts of EPCs did not predict stroke recurrences.

Enhancing the cardiovascular protective effects of a healthy dietary pattern with wolfberry (Lycium barbarum): A randomized controlled trial

The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits. To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore. This is a 16-week, parallel design, randomized controlled trial. All participants (n=40) received dietary counselling to follow healthy dietary pattern recommendations with the wolfberry group given additional instructions to cook and consume 15 g/d whole, dried wolfberry with their main meals. Biomarkers of vascular function (flow-mediated dilation, plasma total nitrate/nitrite, endothelin-1, and intercellular adhesion molecule-1), vascular structure (carotid intima-media thickness) and vascular regeneration (endothelial progenitor cell count, plasma angiopoietin 1 and angiopoietin 2), were assessed at baseline and postintervention. Serum lipid-lipoproteins and blood pressure were evaluated every 4 weeks. All participants showed an improved compliance toward the healthy dietary pattern. This was coupled with marked rises in total nitrate/nitrite concentrations (mean change wolfberry: 3.92±1.73 nmol/mL; control: 5.01±2.55 nmol/L) and reductions in endothelin-1 concentrations (wolfberry: -0.19±0.06 pg/mL; control: -0.15±0.08 pg/mL). Compared with the control which depicted no changes from baseline, the wolfberry group had a significantly higher HDL cholesterol (0.08±0.04 mmol/L), as well as lower Framingham predicted long-term CVD risk (-0.8±0.5%) and vascular age (-1.9±1.0 y) postintervention. No differences were observed in the other vascular health-related outcomes. In middle-aged and older adults, adherence to a healthy dietary pattern improves vascular tone. Incorporating wolfberry to the diet further improves blood lipid-lipoprotein profile and may lower long-term CVD risk. This study was registered at clinicatrials.gov as NCT03535844.

Effects of structured home-based exercise training on circulating endothelial progenitor cells and endothelial function in patients with intermittent claudication.

Exercise training improves walking capacity in patients with intermittent claudication (IC). Endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and endothelial dysfunction could play a role in this process. We measured EPCs and EMPs in a group of 60 patients with IC, and in a control group of 20 individuals without IC, before a treadmill test and 2, 24, and 48 hours after the test. Thirty patients with IC were randomly assigned to perform a 12-week home-based exercise training program. The EPC count, flow-mediated dilation (FMD) of the brachial artery, pain-free walking time (PFWT), and maximum walking time (MWT) were measured at the baseline and after the exercise training program. In patients with IC, EMPs significantly increased 2 hours after the treadmill test, whereas EPCs significantly increased after 24 hours. Among the subjects assigned to complete the training program, we observed a significant increase in the number of EPCs after 12 weeks, as well as an improvement in FMD, PFWT, and MWT. A significant correlation between the variation of EPCs, FMD, and MWT was found. The increase of EPCs and FMD were independent determinants of the walking capacity improvement, without significant interaction. Our results suggest that EPCs mobilization contributes to the improvement of walking capacity in patients with IC undergoing structured physical training. A number of different, partly independent, mechanisms are involved in this process, and our results highlight the potential role of EMPs release and endothelial function improvement. ClinicalTrials.gov Identifier: NCT04302571.

Pleiotropic effect of erythropoiesis-stimulating agents on circulating endothelial progenitor cells in dialysis patients

Recent studies have suggested that erythropoiesis-stimulating agents (ESAs) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. We conducted a 12-week prospective study in 51 dialysis patients; 13 were treated with recombinant human erythropoietin (EPO, 5290.4 ± 586.9IU/week), 16 with darbepoetin (DA, 42.9 ± 4.3µg/week), 12 with epoetin β pegol (CERA, 40.5 ± 4.1µg/week) and 10 with no ESAs. Vascular mediators comprising endothelial progenitor cells (EPCs), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured at 0 and 12weeks. EPCs were measured by flow cytometry as CD45lowCD34+CD133+ cells. The EPC count increased significantly to a greater extent in the EPO group than in the other three group, and increased significantly from 0 to 12weeks in a EPO dose-dependent manner. In both the DA and CERA groups, the EPC count did not change at 12weeks. Serum levels of VEGF, MMP-2 and hs-CRP were not affected by ESA treatment in all groups. In the CERA group, serum ferritin decreased significantly compared to the no-ESA group and correlated with CERA dose, although use of iron was permitted if required during the prospective study period of 12weeks. When patients on dialysis were treated with clinical doses of various ESAs, only EPO induced a significant increase of circulating EPCs from bone marrow, whereas, DA and CERA had no effect.

Circulating Endothelial Progenitor Cells and Their Relation to Thrombosis in Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia.

Thrombosis is a leading cause of morbidity and mortality in paroxysmal nocturnal hemoglobinuria (PNH). Multiple factors are responsible for the thrombotic tendency in these patients. Endothelial progenitorcells (EPCs) originate from primitive hematopoietic stem cells. The EPC count is considered indicative of potential damage and restoration capacity in vascular disease; lower EPC counts are deemed as a risk factor in cardiovascular diseases. We aimed to investigate the count of circulating EPCs in PNH and aplastic anemia (AA) patients receiving eculizumab treatment or not receiving treatment and their relationship with thrombosis. Seventeen PNH patients, 18 AA patients, and 10 healthy volunteers were included in the study. The CD309, CD133, and CD34 antibodies were used to determine counts of circulating EPCs using flowcytometry. EPC levels were compared between the PNH, AA, and healthy control groups. Kolmogorov-Smirnov test. ANOVA, Kruskal-Wallis, and Mann-Whitney U testswereperformedto analyze the quantitative data, while χ2 testing was performed to analyze the qualitative data. Therewasnosignificantdifference in EPC levelsbetweenpatientswithandwithout a history of thrombosis (P > 0.05). Further, therewasnosignificantdifference in thelevels of EPCsbetweenthe AA and PNH groups (P > 0.05). However, there was a significant positive correlation between levels of EPCs and lactate dehydrogenase (LDH) in multivariate analysis (P < 0.05). The study findings suggest that hemolysis promotes vascular endothelial and new blood vessel formation. Increased EPCs in PNH may indirectly indicatevascular endothelial damage in PNH.

Increased number of endothelial progenitor cells in the blood of patients with psoriasis vulgaris.

Psoriasis vulgaris (PsV) is a common dermatosis characterized by excessive activation of neovascularization. Latest research has shown that endothelial progenitor cells (EPCs) are a crucial factor involved in the repair of endothelial injury and formation of new blood vessels, in a process termed postnatal vasculogenesis. However, the exact mechanism of creating psoriatic skin patches and the involvement of EPCs in this process remains unknown. To evaluate the number of EPCs in the blood of patients with PsV, characterized by the expression of specific cell surface markers, including CD45-, CD31+, CD34+ and CD133+. A total of 49 patients suffering from PsV and 40 healthy volunteers were enrolled in the study. The number of EPCs in each of the volunteers' whole blood samples was measured with a FACSCalibur flow cytometer using monoclonal antibodies directed against antigens specific for EPCs. The number of EPCs was significantly higher in patients with psoriasis compared with the controls (p = 0.0007) and inversely correlated with disease severity assessed by PASI score (R = -0.2935, p = 0.0407). Statistical analysis did not show significant relations between the count of EPCs and age, body mass index, gender, disease duration, blood pressure, extent of itching, severity and frequency of pruritus, presence of bruises, vitamin D supplementation and smoking habit. The results of our studies indicate that patients with psoriasis showed an increased mobilization of EPCs compared with healthy individuals which correlated negatively with disease severity.

The detrimental qualitative and quantitative alterations of circulating endothelial progenitor cells in patients with bronchiectasis

BackgroundBronchiectasis is an independent risk factor for cardiovascular disease（CVD）and cardiac dysfunction. Endothelial progenitor cells (EPCs) play a crucial role in maintaining endothelial function, and is inversely correlated with cardiovascular risk factors or cardiac dysfunction. However, the relationship between EPCs and bronchiectasis is unknown. MethodsTwenty-nine patients with stable bronchiectasis and 15 healthy controls were recruited. Fasting venous blood were collected for determining circulating EPC number and activity as well as systemic inflammatory cytokines. ResultsThe number and migratory or proliferative activity of circulating EPCs in bronchiectasis patients were significantly reduced (p < 0.001). In high E-FACED group, the number of circulating EPCs evaluated by cell culture assay and EPC proliferation were decreased (p < 0.05). Similarly, the number and function of circulating EPCs were both reduced in low forced expiratory volume in 1 s (FEV1) or high mMRC group (p < 0.05). There was a significant correlation between circulating EPCs and bronchiectasis disease severity, according to the E-FACED score (p < 0.05), particularly to FEV1 (p < 0.05) and mMRC dyspnea score (p < 0.05). The count and activity of EPCs inversely correlated with hsCRP levels and IL-6 levels (p < 0.01). ConclusionsDeficiencies in the number and function of circulating EPCs are present in patients with bronchiectasis. The changes are related to disease severity and may be partly attributed to systemic inflammation. The current findings may provide novel surrogate evaluation biomarkers and potential therapeutic target for bronchiectasis.