Percentage Of Endothelial Progenitor Cells Research Articles

Caffeine improves systemic lupus erythematosus endothelial dysfunction by promoting endothelial progenitor cells survival.

We studied the role of caffeine intake on endothelial function in SLE by assessing its effect on circulating endothelial progenitor cells (EPCs) both ex vivo in SLE patients and in vitro in healthy donors (HD) treated with SLE sera. We enrolled SLE patients without traditional cardiovascular risks factors. Caffeine intake was evaluated with a 7-day food frequency questionnaire. EPCs percentage was assessed by flow cytometry analysis and, subsequently, EPCs pooled from six HD were co-cultured with caffeine with and without SLE sera. After 7 days, we evaluated cells' morphology and ability to form colonies, the percentage of apoptotic cells by flow cytometry analysis and the levels of autophagy and apoptotic markers by western blot. Finally, we performed a western blot analysis to assess the A2AR/SIRT3/AMPK pathway. We enrolled 31 SLE patients, and observed a positive correlation between caffeine intake and circulating EPCs percentage. HD EPCs treated with SLE sera and caffeine showed an improvement in morphology and in number of EPCs colony-forming units in comparison with those incubated without caffeine. Caffeine was able to restore autophagy and apoptotic markers in HD EPCs as before SLE sera treatment. Finally, caffeine treatment was able to significantly reduce A2AR levels, leading to an increase in protein levels of SIRT3 and subsequently AMPK phosphorylation. Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway.

Associations between Erectile Dysfunction and Vascular Parameters: A Systematic Review and Meta-Analysis.

Erectile dysfunction (ED) is associated with several vascular disorders, but the associations between ED and vascular parameters are still unclear. We analyzed and synthesized a comprehensive range of studies from PubMed, Web of Science, and Scopus regarding the associations between ED and the following measures: ankle-brachial index (ABI), pulse wave velocity (PWV), intima-media thickness (IMT), nitrate-mediated dilation (NMD), flow-mediated dilation (FMD), augmentation index (AI), endothelial progenitor cells (EPCs) and other vascular parameters. Subgroup analysis was conducted according to specific types of parameters. Study quality was assessed by using the Newcastle-Ottawa Scale. Sensitivity analysis was conducted to confirm the robustness of the pooled results. Fifty-seven studies with 7,312 individuals were included. Twenty-eight studies were considered to be high-quality. ED patients had a 0.11 mm higher IMT (95% confidence interval [CI]: 0.07, 0.15), a 2.86% lower FMD (95% CI: -3.56, -2.17), a 2.34% lower NMD (95% CI: -3.37, -1.31), a 2.83% higher AI (95% CI: 0.02, 5.63), a 1.11 m/s higher PWV (95% CI: 0.01, 2.21), and a 0.72% lower percentage of EPCs (95% CI: -1.19, -0.24) compared to those without ED. However, ABI was similar between ED patients and non-ED individuals. According to sensitivity analysis, the pooled results were robust. Our study confirmed the associations between ED and several vascular parameters and highlighted the importance of prevention and management of vascular and endothelial dysfunction in ED patients.

Endothelial Progenitor Cells and Macrophage Subsets Recruitment in Postischemic Mouse Hind Limbs

Introduction: Peripheral arterial disease (PAD) occurs from atherosclerotic obstruction of arteries in the lower extremities. Restoration of perfusion requires angiogenesis and arteriogenesis through migration and differentiation of endothelial progenitor cells (EPCs) and macrophages at the site of injury. The time of recruitment has not been fully investigated. In this study, we investigated the infiltration of these cells in murine hind limb ischemia (HLI) model of PAD. Methods: EPCs and M1-like and M2-like macrophages from ischemic skeletal muscles were quantified by flow cytometry at day-0, 1, 3, 7, and 14 post-HLI. Results: The abundance of EPCs increased from day 1 and was highest on day 7 until day 14. M1-like population similarly increased and was highest on day 14 during the experiment. M2-like population was significantly greater than M1-like at baseline but surpassed the highest value of M1-like by day 7 during the experiment. Muscle regeneration and capillary density also increased and were highest at days 3 and 7, respectively, during the experiment. All mice achieved near full perfusion recovery by day 14. Conclusion: Thus, we observed a gradual increase in the percentage of EPC’s and this was temporally paralleled with initial increase in M1-like followed by sustained increased in M2-like macrophages and perfusion recovered post-HLI.

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.

Physalis angulata Leaf Ethanol Extract Reduces Oxidative Stress and Improves Endothelial Progenitor Cells in L-NAME-Induced Hypertensive Rats

This study aimed to evaluate the effects of ciplukan (Physalis angulata L.) leaf ethanol extract on L-NG-nitroarginine methyl ester (L-NAME)-induced hypertensive rats. We randomly divided twenty-five Wistar rats into five groups. The sham group was given a PBS injection. The hypertensive group was injected with L-NAME on days 1 to 28. Three groups of hypertensive rats were given the extract on days 4 to 28. Blood pressure was measured using the tail-cuff method on days 0, 4, 10, and 27. The endothelial progenitor cells (EPCs) in the blood were measured by flow cytometry as a percentage of circulating angiogenic cells (CACs, CD34+/CD309+/CD45+) and endothelial colony-forming cells (ECFCs, CD34+/CD309+/CD45-). Serum NO and MDA levels, as well as serum SOD activity, were measured colorimetrically. Serum TNF-α levels were measured by the ELISA method. The ciplukan leaf extract reduced systolic and diastolic blood pressure, reduced the percentage of EPCs in the blood, increased serum NO levels, reduced MDA levels, increased serum SOD activity, and reduced serum TNF-α levels in L-NAME-induced hypertensive rats. It is concluded that ciplukan ethanol leaf extract exerts protective effects on L-NAME-induced hypertensive rats. These study results can strengthen the scientific basis of using ciplukan leaf ethanol extract to treat hypertension.

Circulating endothelial progenitor cells from septic patients are associated with different infectious organisms.

In sepsis, endothelial progenitor cells (EPCs) play a central role in the repair of endothelial injury by enhancing the processes of re-endothelialization and angiogenesis. However, the surface markers of EPCs have yet to be standardized, and Changes of EPCs in quantities and functions with different infectious organisms are still unclear. This study explored the relationship between the percentages of EPCs and various infectious organisms in patients with sepsis. Thirty-nine septic patients and 20 healthy controls were enrolled in this study. The percentages of CD34+/KDR+, CD133+/KDR+, CD34+/CD133+/KDR+, CD34+, CD133+, and KDR+ cells in different groups of septic patients and the healthy controls were analyzed by flow cytometry. The peripheral blood of septic patients had higher percentages of EPCs than that of the healthy controls. There were no significant differences in the percentages of EPCs between the sepsis and septic shock groups, nor between the survival group and the non-survival group. Additionally, the percentages of CD34+/CD133+/KDR+ cells in the gram-positive bacteremia group were significantly higher than those in the gram-negative bacteremia group and the negative blood culture group. The percentage of KDR+ cells in both the gram-positive bacteremia group and the gram-negative bacteremia group was significantly higher than that in the negative blood culture group. The percentages of circulating EPCs in patients with sepsis are associated with different infectious organisms.

The IMMENSE Study: The Interplay Between iMMune and ENdothelial Cells in Mediating Cardiovascular Risk in Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3+CD31+CXCR4+ T cells (Tang), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a Tang subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between Tang subpopulations and endothelial cells in a group of young SLE patients without previous cardiovascular events. Twenty SLE female patients and 10 healthy controls (HCs) were recruited. Flow cytometric analysis of endothelial progenitor cells (EPCs) and Tang subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)-γ were measured. Human umbilical vein endothelial cells (HUVECs) proliferation and pro-inflammatory phenotype in response to subjects’ serum stimulation were also evaluated. Results showed that the percentage of Tang and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28null cells among Tang subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to Tang cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of Tang and inversely related to the CD28null Tang subsets. We indirectly evaluated the role of the Tang subset on the endothelium upon stimulation with serum from subjects with a low percentage of Tang CD3+ cells in HUVECs. HUVECs displayed pro-inflammatory phenotype with up-regulation of mRNA for IL-6, intercellular adhesion molecule (ICAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Cell proliferation rate was directly related to IL-8 serum levels and EPC percentage. In highly selected young SLE patients without previous CV events, we found that the deterioration of Tang compartment is an early event in disease course, preceding the development of an overt cardiovascular disease and potentially mediated by SLE-specific mechanisms. The overcome of the CD28null subset exerts detrimental role over the Tang phenotype, where Tang could exert an anti-inflammatory effect on endothelial cells and might orchestrate via IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate.

Circulating exosomal miR-144-3p inhibits the mobilization of endothelial progenitor cells post myocardial infarction via regulating the MMP9 pathway.

Background: The angiogenesis post myocardial infarction (MI) is compromised in diabetes. MiR-144-3p is reported to be highly expressed in circulating exosomes of diabetic patients, implying its role in diabetic complications. However, whether circulating exosomes and enriched miR-144-3p are involved in the impaired neovascularization in diabetes and the underlying mechanism is unclear.Results: DMexo and miR-144-3p mimic-treated MSCs had elevated miR-144-3p levels and decreased MMP9, Ets1 and PLG expression. The percentage of EPCs were relatively lower in DMexo-treated or agomir-treated MI mice compared with MI mice. Finally, the luciferase assay confirmed the direct binding between miR-144-3p and Ets1.Conclusion: Exosomal miR-144-3p could impair the mobilization ability of EPCs, which was associated with impaired ischemia-induced neovascularization.Methods: Circulating exosomes were isolated from Streptozotocin (STZ)-induced mice. In vitro, mesenchymal stem cells (MSCs) were incubated with exosomes from diabetic mice (DMexo), and miR-144-3p mimic or inhibitor. miR-144-3p, and MMP9 pathway were measured using qPCR and immunoblotting. In vivo, MI mice induced by left anterior descending ligation were treated with DMexo, as well as miR-144-3p agomir. Flow cytometry was used to profile endothelial progenitor cells (EPCs) in peripheral blood and bone marrow post 24 hours respectively.

Dietary Supplemental Glutamine Enhances the Percentage of Circulating Endothelial Progenitor Cells in Mice with High-Fat Diet-Induced Obesity Subjected to Hind Limb Ischemia.

This study investigated whether glutamine (GLN) pretreatment can enhance circulating endothelial progenitor cells (EPCs) and attenuate inflammatory reaction in high-fat diet-induced obese mice with limb ischemia. Mice were assigned to a normal control (NC), high-fat control (HC), limb ischemia (HI), and GLN limb ischemia (HG) groups. The NC group provided chow diet and treated as a negative control. Mice in the HC and HI groups were fed a high-fat diet which 60% energy provided by fat for 8 weeks. Mice in the HG group were fed the same diet for 4 weeks and then transferred to a high-fat diet with 25% of total protein nitrogen provided as GLN to replace part of the casein for the subsequent 4 weeks. After feeding 8 weeks, mice in the HC group were sham-operated, while the HI and HG groups underwent an operation to induce limb ischemia. All mice except the NC group were euthanized on either day 1 or 7 after the operation. The results showed that the 8 weeks' high-fat diet feeding resulted in obesity. The HG group had higher circulating EPCs on day 1 while muscle vascular endothelial growth factor, matrix metalloproteinase-9, and hypoxia-inducible factor-1 gene expressions were higher on day 7 postischemia than those of the HI group. The superoxide dismutase activity and reduced glutathione content in affected muscles were higher, whereas mRNA expressions of interleukin-6 and tumor necrosis factor-α were lower in the HG than those in the HI group. These findings suggest that obese mice pretreated with GLN-supplemented high-fat diet increased circulating EPC percentage, enhanced the antioxidant capacity, and attenuated inflammatory reactions in response to limb ischemia.

Circulating hematopoietic stem cells, endothelial progenitor cells and cancer stem cells in hepatocellular carcinoma patients: contribution to diagnosis and prognosis

Background and aim: Circulating hematopoietic stem cells (HSCs), circulating endothelial progenitor cells (EPCs) and cancer stem cells (CSCs) contribute to tumor development and progression and can predict patient outcome. The aim of this study was to investigate the frequency of circulating HSCs, EPCs and CSCs in the peripheral blood of patients with hepatocellular carcinoma (HCC) and to explore their potential prognostic significance for HCC patients.Methods: The study included 30 HCC patients and 20 healthy controls. The HSCs and EPCs were enumerated with CD45, CD34, CD133, CD144 markers, while CSCs were enumerated with CD45, CD44, CD133 markers using flow cytometry.Results: The mean percentages of circulating HSCs were significantly lower in HCC patients than the controls (p = .001), whereas the mean percentages of EPCs within the HSCs subpopulation were significantly higher in the HCC patients than the controls (p = .002). The absolute count of CSCs within 100,000 peripheral blood mononuclear cells was 23.5 ± 3.4 in the HCC patients. Also, the mean percentages of circulating HSCs, EPCs and the number of CSCs were significantly increased in patients with multiple hepatic focal lesions than in patients with a single hepatic focal lesion. Both circulating HSCs and EPCs showed significant positive correlation with the level of AFP and with the numbers of CSCs. In the meantime, the numbers of CSCs revealed significant direct correlation with ALT, AST and AFP levels. The one-year overall survival (OS) of the patients was 77.5%. High levels of CSCs, HSCs and EPCs at diagnosis were all associated with worse outcome for the HCC patients.Conclusions: Significant changes in the levels of the circulating HSCs, EPCs and CSCs occur in HCC. These changes help the diagnosis and the prediction of HCC outcome, as higher levels of these cells are associated with worse OS.

FEATURES OF THE CONTENT OF ENDOTHELIAL PROGENITOR CELLS IN UMBILICAL CORD BLOOD OF PRE-TERM AND FULL-TERM NEWBORNS

The purpose of the study : determination of content of circulating endothelial cellsin umbilical cord blood in orderto assessthe regenerative potential of the endothelium in newborns. 29 newborn babies were examined: 18 pre-term infants (gestational age 30–35 weeks) and 11 full-term infants (gestational age 38–41 weeks). Determination of the number of circulating endothelial cells was determined in mixed umbilical cord blood of all children their phenotyping was carried out by cytofluorometry method using fluorochromes-labeled monoclonal antibodies. Circulating endothelial cells were defined as CD45–, CD133+, VEGFR2, CD34–, endothelial progenitor cells were defined as CD45–, CD133+, VEGFR2+, CD34+. It was revealed that in umbilical cord blood of pre-term infants was decreased both the total number of circulating endothelial cells and endothelial progenitor cells compared to full-term infants. Moreover, in preterm infants was observed higher percentage of endothelial progenitor cells, rather than mature endothelial cells. In blood of full-term infants was observed higher percentage of mature endothelial cells compared to endothelial progenitor cells and their number increases with increasing birth weight of the newborn. The decrease in the number of endothelial progenitor cells in pre-term infants is associated with impaired endothelial function. CD45–CD133+VEGFR2+CD34+ cells are involved in reparation of damaged endothelium and reduction in their number in the blood reflects the reduction of its regenerative potential.

Arginine administration increases circulating endothelial progenitor cells and attenuates tissue injury in a mouse model of hind limb ischemia/reperfusion.

This study investigated whether the administration of L-Arginine, the precursor of nitric oxide, increases the percentages of blood endothelial progenitor cells and protects against ischemia/reperfusion induced inflammatory response in a mouse model of hind-limb IR injury. C57BL/6 mice were randomized to one normal-control and four ischemia/reperfusion groups. The normal-control group did not undergo an ischemia/reperfusion procedure but mice in the ischemia/reperfusion groups were subjected to 150 min of unilateral hind-limb ischemia. The ischemia/reperfusion groups were subjected to either intravenous saline or L-Arginine (300 mg/kg body weight) administration before reperfusion and then sacrificed at either 24 h or 48 h after reperfusion. Blood and muscle tissues were collected for analysis. Ischemia/reperfusion injury led to a significant decrease in the percentage of blood endothelial progenitor cells and plasma nitric oxide concentration but plasma interleukin-6 levels and gene expression of inflammatory cytokines in injured muscle tissue were elevated. In contrast to the saline groups, those with L-Arginine administration were able to maintain a normal level of blood endothelial progenitor cells. In addition, after reperfusion, concentrations of nitric oxide, matrix metallopeptidase-9, and vascular endothelial growth factor in plasma were upregulated but keratinocyte-derived chemokine and monocyte chemoattractant protein-1 messenger RNA expressions in muscle were attenuated 48 h after reperfusion. Histologic findings also demonstrated a significant reduction of ischemia/reperfusion-induced muscle injury when L-Arginine was administered. A single dose of L-Arginine administration before reperfusion increases the percentage of endothelial progenitor cells and reduces the inflammatory reaction locally and systemically after ischemia/reperfusion injury.

Arginine pretreatment enhances circulating endothelial progenitor cell population and attenuates inflammatory response in high-fat diet–induced obese mice with limb ischemia

Obesity is a global health problem with an up-regulated inflammatory reaction. Obesity-induced endothelial progenitor cells (EPCs) dysfunction is associated with vascular complications that may contribute to critical limb ischemia. Arginine (Arg) is an amino acid with immune-modulatory property and has been found to promote EPCs mobilization in disease conditions. Thus in the present investigation, we hypothesized that arginine given to a murine model of diet-induced obesity would increase circulating EPCs and mitigate the inflammatory reactions in response to limb ischemia. Mice were divided into normal group (NC), high-fat group (HC), and high-fat Arg group (HA). Mice in the HC group were fed with a diet containing 60% energy as fat for 8 weeks, while HA group were initially fed with the same high-fat diet for 4 weeks and later shifted to a high-fat diet enriched with 2% Arg for the remaining 4 weeks. Then mice in the HC and HA groups underwent ischemic operations and were euthanized at either day 1 or day 7 after limb ischemia. The results showed that, compared to the ischemic HC group, the ischemic HA group had higher circulating EPCs at day 1 post-ischemia and higher muscle stromal cell-derived factor-1 and interleukin (IL)-10 mRNA expressions at day 7 after ischemia. In contrast, plasma leptin concentration and expressions of IL-1β and tumor necrosis factor-α mRNAs by adipocytes were down-regulated. These findings suggest that obese mice treated with Arg-containing high-fat diet enhanced circulating EPCs percentage and attenuated inflammatory reaction in response to limb ischemia.

Новые данные о локализации V2‑рецептора вазопрессина у пациентов с гипертонической болезнью 2–3‑й степени и здоровых лиц

to compare the percentage of endothelial progenitor cells and exfoliated endothelial cells in the total number of cells of lymphocytic fraction in patients with essential hypertension (EH) and practically healthy persons, and to evaluate expression of vasopressin V2 receptor on the endothelial progenitor cells. We examined 20 patients with 2-3‑degree EH and 10 practically healthy persons. Clinical examination of patients included electrocardiography, echocardiography, biochemical blood analysis / isolation of Endothelial progenitor cells were isolated from blood plasma. Immunocytochemical study was performed by the method of combined staining using primary and secondary antibodies. Microscope Olympus FV10i was used for confocal microscopy of endothelial progenitor cells and exfoliated endothelial cells. The percentage of endothelial progenitor cells (phenotype CD31+СD133+) in the total number of cells of the lymphocytic fraction was significantly higher in patients with EH in comparison with healthy individuals (p=0.013 and p=0.008 for 2 and 3 degrees EH, respectively). The percentage of exfoliated endothelial cells (phenotype СD31+СD133-) in the total number of cells of the lymphocytic fraction was also significantly higher in patients with EH in comparison with healthy individuals (p=0.008 and p=0.019 for 2 and 3 degrees EH, respectively). For the first time we identified the localization of vasopressin V2-receptor on the membrane of endothelial progenitor cells. In patients with 2-3 degrees EH the percentage of endothelial progenitor cells and exfoliated endothelial cells of the total number of cells of the lymphocytic fraction is significantly was found to be increased. Localization of vasopressin V2‑receptor on the membrane of endothelial progenitor cells was detected.

The ratio of circulating regulatory cluster of differentiation 4 T cells to endothelial progenitor cells predicts clinically significant acute rejection after heart transplantation

The aim of this study was to determine the value of the ratio of the percentage of circulating regulatory cluster of differentiation 4 T cells (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC ratio) for predicting clinically significant acute rejection. Peripheral blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using flow cytometry at a mean of 42 ± 13 days after transplant. The primary end point was clinically significant acute rejection, defined as an event that led to an acute augmentation of immunosuppression in conjunction with an International Society for Heart and Lung Transplantation grade ≥ 2R in a right ventricular endomyocardial biopsy specimen or non-cellular rejection (specimen-negative rejection) with hemodynamic compromise (decrease in left ventricular ejection fraction by > 25%). Significant rejection occurred in 27 recipients (29.7%) during a median of 49.4 months (interquartile range, 37.0-62.0 months). The mean %Tregs and %EPCs were not significantly different between those with and without an episode of significant rejection, but the mean Treg/EPC ratio was significantly lower in recipients with significant rejection (44.9 vs 106.7, p = 0.001). Receiver operating characteristic curve analysis showed anarea under the curve value for significant rejection for a Treg/EPC ratio of 0.712. The best cutoff value of the Treg/EPC ratio that distinguished between those with or without significant rejection was ≤ 18 by receiver operating characteristic curve analysis. Kaplan-Meier analysis revealed that patients with a Treg/EPC ratio of ≤ 18 had a significantly higher rate of rejection than those with a Treg/EPC ratio > 18 (61.5% vs 16.9%, log-rank p < 0.0001). A low Treg/EPC ratio was an independent predictor of significant rejection. A low Treg/EPC ratio measured soon after heart transplantation is an independent predictor of acute rejection. The Treg/EPC ratio has potential as an early biomarker after heart transplantation for predicting acute rejection.

Bone Marrow-Derived Stem Cell Populations Are Differentially Regulated by Thyroid or/and Ovarian Hormone Loss.

Bone marrow-derived stem cells (BMDSCs) play an essential role in organ repair and regeneration. The molecular mechanisms by which hormones control BMDSCs proliferation and differentiation are unclear. Our aim in this study was to investigate how a lack of ovarian or/and thyroid hormones affects stem cell number in bone marrow lineage. To examine the effect of thyroid or/and ovarian hormones on the proliferative activity of BMDSCs, we removed the thyroid or/and the ovaries of adult female rats. An absence of ovarian and thyroid hormones was confirmed by Pap staining and Thyroid Stimulating Hormone (TSH) measurement, respectively. To obtain the stem cells from the bone marrow, we punctured the iliac crest, and aspirated and isolated cells by using a density gradient. Specific markers were used by cytometry to identify the different BMDSCs types: endothelial progenitor cells (EPCs), precursor B cells/pro-B cells, and mesenchymal stem cells (MSCs). Interestingly, our results showed that hypothyroidism caused a significant increase in the percentage of EPCs, whereas a lack of ovarian hormones significantly increased the precursor B cells/pro-B cells. Moreover, the removal of both glands led to increased MSCs. In conclusion, both ovarian and thyroid hormones appear to have key and diverse roles in regulating the proliferation of cells populations of the bone marrow.

Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia

Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue ischemia may occur with diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral glutamine (GLN) supplementation on circulating EPC mobilization and expression of tissue EPC-releasing markers in diabetic mice subjected to limb ischemia. Diabetes was induced by a daily intraperitoneal injection of streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9 and the circulating EPC percentage increased after limb ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia-inducible factor-1 and vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb ischemia.

Short-term atorvastatin therapy improves arterial stiffness of middle-aged systemic lupus erythematosus patients with pathological pulse wave velocity.

Objectives Statins have been proposed as a potential treatment for systemic lupus erythematosus (SLE) due to their immunomodulatory properties, their role restoring endothelial function and preventing atherosclerosis. We evaluate the effect of a short period treatment with a low dose of atorvastatin and its withdrawal on early stage subclinical atherosclerosis. Methods Thirty-seven SLE females received 20 mg/day atorvastatin during eight weeks. At baseline, at the end of treatment and six months after atorvastatin withdrawal, disease activity, subclinical atherosclerosis -assessed by measuring carotid-femoral pulse wave velocity (PWV) - and quantification of circulating endothelial progenitor cells (EPC) - as a surrogate biological marker of subclinical atherosclerosis - were carried out. Results The group of SLE patients with baseline pathological arterial stiffness showed a significant decrease of PWV after atorvastatin therapy (8.43 ± 1.45 m/s vs 7.42 ± 1.06 m/s; p = 0.002) that is maintained six months after treatment finished. Only patients of the middle-aged group showed a nearly significant decrease in the PWV measured along the study (7.16 ± 1.23 m/s vs 6.76 ± 0.82 m/s; p = 0.05). Atorvastatin induced a significant decrease in the circulating EPC percentage (0.65 ± 0.67 vs 0.40 ± 0.31; p = 0.023) as well as a downward trend of disease activity that it is observed by a decrease in SLE disease activity index simultaneously with an increase in C3 complement and significant decrease in serum concentration of vascular endothelial grow factor (VEGF) and sVCAM-1. Conclusions Short-term atorvastatin therapy reduces arterial stiffness of SLE patients with baseline pathological PWV, who are mainly in the group of middle-aged patients. Further studies are needed to determine whether these patients would benefit from statin therapy in preventing cardiovascular events.

Glutamine Administration Modulates Endothelial Progenitor Cell and Lung Injury in Septic Mice.

This study investigated the effects of glutamine (GLN) administration on circulating endothelial progenitor cells (EPCs) and lung angiopoietin (Ang) gene expressions in polymicrobial sepsis. Mice were randomly assigned to a normal control group (NC), septic saline group (SS), and septic GLN group (SG). All mice were fed with a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The mice in SS group were injected with saline, whereas SG group administered 0.75 g GLN/kg body weight once via tail vein 1 h after CLP. Mice were killed 24 and 48 h after CLP. Their blood and lungs were collected for further analysis. The results showed that, compared with normal mice, sepsis resulted in higher C-X-C motif chemokine-12, vascular endothelial growth factor, nitric oxide levels, and a higher circulating EPC percentage. In addition, inflammatory cytokine concentrations and Ang-2 gene expression were upregulated in lung tissues. GLN administration enhanced the mobilization of EPC, and downregulated inflammatory cytokine production and the Ang-2 gene expressions in lungs. Histopathological findings showed that the extent of inflammatory lesions of the lung alveolar was less severe in the SG group than the SS group after CLP. Our results suggest that a single dose of intravenous GLN administration after initiation of sepsis promotes the mobilization of circulating EPC, and modulates the balance of Ang-Tie2 axis that may improve the vascular function, ameliorate inflammation, and protect lung injury against polymicrobial sepsis.

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals

ObjectivesAcute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. MethodsThis was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. ResultsBaseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. ConclusionMedium-term administration of OPE an improvement in FMD and circulating EPCs.