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Sample records for circulating vascular progenitors

  1. Cord blood-circulating endothelial progenitors for treatment of vascular diseases.

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    Lavergne, M; Vanneaux, V; Delmau, C; Gluckman, E; Rodde-Astier, I; Larghero, J; Uzan, G

    2011-04-01

    Adult peripheral blood (PB) endothelial progenitor cells (EPC) are produced in the bone marrow and are able to integrate vascular structures in sites of neoangiogenesis. EPCs thus represent a potential therapeutic tool for ischaemic diseases. However, use of autologous EPCs in cell therapy is limited by their rarity in adult PB. Cord blood (CB) contains more EPCs than PB, and they are functional after expansion. They form primary colonies that give rise to secondary colonies, each yielding more than 10(7) cells after few passages. The number of endothelial cells obtained from one unit of CB is compatible with potential clinical application. EPC colonies can be securely produced, expanded and cryopreserved in close culture devices and endothelial cells produced in these conditions are functional as shown in different in vitro and in vivo assays. As CB EPC-derived endothelial cells would be allogeneic to patients, it would be of interest to prepare them from ready-existing CB banks. We show that not all frozen CB units from a CB bank are able to generate EPC colonies in culture, and when they do so, number of colonies is lower than that obtained with fresh CB units. However, endothelial cells derived from frozen CB have the same phenotypical and functional properties than those derived from fresh CB. This indicates that CB cryopreservation should be improved to preserve integrity of stem cells other than haematopoietic ones. Feasibility of using CB for clinical applications will be validated in porcine models of ischaemia.

  2. From Here to There, Progenitor Cells and Stem Cells Are Everywhere in Lung Vascular Remodeling.

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    Heise, Rebecca L; Link, Patrick A; Farkas, Laszlo

    2016-01-01

    The field of stem cell biology, cell therapy, and regenerative medicine has expanded almost exponentially, in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), or pulmonary arterial hypertension (PAH). Extensive research activity is exploring the lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications. It is becoming more and more clear that progress in mechanobiology will help to understand the various influences of physical forces and extracellular matrix composition on the phenotype and features of the progenitor cells and stem cells. The current review provides an overview of current concepts in the field. PMID:27583245

  3. From here to there, progenitor cells and stem cells are everywhere in lung vascular remodeling

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    Rebecca L. Heise

    2016-08-01

    Full Text Available The field of stem cell biology, cell therapy and regenerative medicine has expanded almost exponentially in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD, chronic obstructive pulmonary disease (COPD, idiopathic pulmonary fibrosis (IPF or pulmonary arterial hypertension (PAH. Extensive research activity is exploring lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications. It is becoming more and more clear that progress in mechanobiology will help to understand the various influences of physical forces and extracellular matrix composition on the phenotype and features of the progenitor cells and stem cells. The current review provides an overview of current concepts in the field.

  4. Pro-angiogenic Hematopoietic Progenitor Cells and Endothelial Colony Forming Cells in Pathological Angiogenesis of Bronchial and Pulmonary Circulation

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    Duong, Heng; Erzurum, Serpil; Asosingh, Kewal

    2011-01-01

    Dysregulation of angiogenesis is a common feature of many disease processes. Vascular remodeling is believed to depend on the participation of endothelial progenitor cells, but the identification of endothelial progenitors in postnatal neovascularization remains elusive. Current understanding posits a role for circulating pro-angiogenic hematopoietic cells, which interact with local endothelial cells to establish an environment that favors angiogenesis in physiologic and pathophysiologic resp...

  5. Smoking decreases the level of circulating CD34+ progenitor cells in young healthy women - a pilot study

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    Baumann Gert

    2010-05-01

    Full Text Available Abstract Background Decreased levels of circulating bone marrow-derived progenitor cells have been associated with risk factors and cardiovascular diseases. Smoking is the most important modifiable risk factor for atherosclerosis in young women. The aim of this pilot study was to assess in healthy premenopausal women without other risk factors for cardiovascular disease the influence of nicotine abuse on the number of circulating progenitor cells in relation to endothelial function. Methods The number of endothelial progenitor cells, measured as colony-forming units in a cell-culture assay (EPC-CFU and the number of circulating CD34 + and CD34 + /CD133 + cells, measured by flow cytometry, was estimated in 32 women at the menstrual phase of the menstrual cycle. In addition, flow-mediated dilation (FMD was assessed as a marker for vascular function. In a subgroup of these women (n = 20, progenitor cells were also investigated at the mid-follicular and luteal phases of the menstrual cycle. Results Compared to non-smokers, the abundance of circulating CD34 + cells was significantly lower in smoking women in the menstrual, mid-luteal, and mid-follicular phases of the menstrual cycle. The number of CD34 + progenitor cells was revealed to have significant positive correlation with FMD in young healthy women, whereas CD34 + /CD133 + progenitor cells and EPC-CFU showed no significant correlation. Conclusion The number of CD34 + progenitor cells positively correlates with FMD in young healthy women and is decreased by smoking.

  6. Dysregulation of Vascular Endothelial Progenitor Cells Lung-Homing in Subjects with COPD

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    Brittany M. Salter

    2016-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by fixed airflow limitation and progressive decline of lung function and punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating mobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular endothelial progenitor cells (VEPCs are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex-smokers with diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted primitive hemopoietic progenitors (HPCs and VEPC were enumerated by flow cytometry. Migration and adhesive responses to fibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood, VEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups in either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal cell-derived factor-1alpha (SDF-1α compared to normal controls. This was associated with greater numbers of CXCR4+ progenitors in sputum from COPD. Increased migrational responsiveness of progenitor cells may promote lung-homing of VEPC in COPD which may disrupt maintenance and repair of the airways and contribute to COPD disease pathogenesis.

  7. Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

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    Liu-mei Hu; Guo-xu Xu; Guo-tong XU; Wei-ye Li; Xia Lei; Bo Ma; Yu Zhang; Yan Yan; Ya-lan Wu; Ge-zhi Xu; Wen Ye; Ling Wang

    2011-01-01

    Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor(EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).Methods EPOR positive circulating progenitor cells (CPCs: CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif-erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR+ CPCs and EPOR+ EPCs were reduced remarkably in NPDR compared with the control group (both P<0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR+ CPCs in CPCs (NPDR vs.control, P< 0.01) and that of EPOR+ EPCs in EPCs (NPDR vs. control, P< 0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the im-paired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR+ EPCs associated with ischemia.

  8. The level of circulating endothelial progenitor cells may be associated with the occurrence and recurrence of chronic subdural hematoma

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    Yan Song

    2013-01-01

    Full Text Available OBJECTIVES: The onset of chronic subdural hematoma may be associated with direct or indirect minor injuries to the head or a poorly repaired vascular injury. Endothelial progenitor cells happen to be one of the key factors involved in hemostasis and vascular repair. This study was designed to observe the levels of endothelial progenitor cells, white blood cells, platelets, and other indicators in the peripheral blood of patients diagnosed with chronic subdural hematoma to determine the possible relationship between the endothelial progenitor cells and the occurrence, development, and outcomes of chronic subdural hematoma. METHOD: We enrolled 30 patients with diagnosed chronic subdural hematoma by computer tomography scanning and operating procedure at Tianjin Medical University General Hospital from July 2009 to July 2011. Meanwhile, we collected 30 cases of peripheral blood samples from healthy volunteers over the age of 50. Approximately 2 ml of blood was taken from veins of the elbow to test the peripheral blood routine and coagulation function. The content of endothelial progenitor cells in peripheral blood mononuclear cells was determined by flow cytometry. RESULTS: The level of endothelial progenitor cells in peripheral blood was significantly lower in preoperational patients with chronic subdural hematomas than in controls. There were no significant differences between the two groups regarding the blood routine and coagulation function. However, the levels of circulating endothelial progenitor cells were significantly different between the recurrent group and the non-recurrent group. CONCLUSIONS: The level of circulating endothelial progenitor cells in chronic subdural hematoma patients was significantly lower than the level in healthy controls. Meanwhile, the level of endothelial progenitor cells in recurrent patients was significantly lower than the level in patients without recurrence. Endothelial progenitor cells may be related to the

  9. Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

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    Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

    2012-06-01

    We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. PMID:22370181

  10. Characterization of vascular endothelial progenitor cells from chicken bone marrow

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    Bai Chunyu

    2012-05-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC are a type of stem cell used in the treatment of atherosclerosis, vascular injury and regeneration. At present, most of the EPCs studied are from human and mouse, whereas the study of poultry-derived EPCs has rarely been reported. In the present study, chicken bone marrow-derived EPCs were isolated and studied at the cellular level using immunofluorescence and RT-PCR. Results We found that the majority of chicken EPCs were spindle shaped. The growth-curves of chicken EPCs at passages (P 1, -5 and -9 were typically “S”-shaped. The viability of chicken EPCs, before and after cryopreservation was 92.2% and 81.1%, respectively. Thus, cryopreservation had no obvious effects on the viability of chicken EPCs. Dil-ac-LDL and FITC-UAE-1 uptake assays and immunofluorescent detection of the cell surface markers CD34, CD133, VEGFR-2 confirmed that the cells obtained in vitro were EPCs. Observation of endothelial-specific Weibel-Palade bodies using transmission electron microscopy further confirmed that the cells were of endothelial lineage. In addition, chicken EPCs differentiated into endothelial cells and smooth muscle cells upon induction with VEGF and PDGF-BB, respectively, suggesting that the chicken EPCs retained multipotency in vitro. Conclusions These results suggest that chicken EPCs not only have strong self-renewal capacity, but also the potential to differentiate into endothelial and smooth muscle cells. This research provides theoretical basis and experimental evidence for potential therapeutic application of endothelial progenitor cells in the treatment of atherosclerosis, vascular injury and diabetic complications.

  11. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

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    Rosa L.E. Loon

    2015-08-01

    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  12. Circulating endothelial progenitor cells in kidney transplant patients.

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    Giovana S Di Marco

    Full Text Available BACKGROUND: Kidney transplantation (RTx leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs. METHODS: We analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males. RTx patients received a calcineurin inhibitor (CNI-based (65% or a CNI-free therapy (35% and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1 levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+ and CD26+ cells were determined by flow cytometry. RESULTS: Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1--a cytokine responsible for EPC mobilization--is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1. CONCLUSIONS: We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in

  13. Biological behaviour and role of endothelial progenitor cells in vascular diseases

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    ZHANG Qiu-hua; SHE Ming-peng

    2007-01-01

    Obiective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007.The search term was "endothelial progenitor cells".Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used.Results Progenitor cells in bone marrow,peripheral blood and adventitia can differentiate into mature endothelial cells (ECs).The progenitor cells,which express certain surface markers including AC133,CD34 and KDR,enable restoration of the microcirculation and ECs when injury or ischaemia occurs.Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development.Moreover,their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors.Impairment of the progenitor cells might limit the regenerative capacity,even lead to the development of atherosclerosis or other vascular diseases.Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases.However,many challenges remain in understanding differentiation of endothelial progenitor cells,their mobilization and revascularization.

  14. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

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    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. PMID:27016579

  15. Update on the pathogenesis of Scleroderma: focus on circulating progenitor cells [version 1; referees: 2 approved

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    Alexandra Maria Giovanna Brunasso

    2016-04-01

    Full Text Available In systemic sclerosis (SSc, the development of fibrosis seems to be a consequence of the initial ischemic process related to an endothelial injury. The initial trigger event in SSc is still unknown, but circulating progenitor cells (CPCs might play a key role. Such cells have the ability to traffic into injury sites, exhibiting inflammatory features of macrophages, tissue remodeling properties of fibroblasts, and vasculogenesis functions of endothelial cells. The different subsets of CPCs described thus far in SSc arise from a pool of circulating monocyte precursors (CD14+ cells and probably correspond to a different degree of differentiation of a single cell of origin. Several subsets of CPCs have been described in patients with SSc, all have a monocytic origin but may or may not express CD14, and all of these cells have the ability to give origin to endothelial cells, or collagen (Col-producing cells, or both. We were able to identify six subsets of CPCs: pluripotent stem cells (CD14+, CD45+, and CD34+, monocyte-derived multipotential cells (MOMCs or monocyte-derived mesenchymal progenitors (CD14+, CD45+, CD34+, Col I+, CD11b+, CD68+, CD105+, and VEGFR1+, early endothelial progenitor cells (EPCs or monocytic pro-angiogenic hematopoietic cells or circulating hematopoietic cells (CD14+, CD45+, CD34low/−, VEGFR2+/−, CXCR4+, c-kit+, and DC117+, late EPCs (CD14−, CD133+, VEGFR2+, CD144+ [VE-cadherin+], and CD146+, fibroblast-like cells (FLCs/circulating Col-producing monocytes (CD14+, CD45+, CD34+/−, and Col I+, and fibrocytes (CD14−, CD45+, CD34+, Col I+, and CXCR4+. It has been demonstrated that circulating CD14+ monocytes with an activated phenotype are increased in patients with SSc when compared with normal subjects. CD14+, CD34+, and Col I+ spindle-shaped cells have been found in increased numbers in lungs of SSc patients with interstitial lung disease. Elevated blood amounts of early EPCs have been found in patients with SSc by

  16. Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.

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    Eduardo K Moioli

    Full Text Available Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs and mesenchymal stem/progenitor cells (MSCs were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP scaffolds, followed by infusion of gel-suspended CD34(+ hematopoietic cells. Co-transplantation of CD34(+ HSCs and CD34(- MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromised mice yielded vascularized tissue. The average vascular number of co-transplanted CD34(+ and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34(+ cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34(+ cells. Based on additional in vitro results of endothelial differentiation of CD34(+ cells by vascular endothelial growth factor (VEGF, we adsorbed VEGF with co-transplanted CD34(+ and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34(+ cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone

  17. Predisposing factors in posterior circulation infarcts: a vascular morphological assessment

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    Coban, Goekcen; Cifci, Egemen; Yildirim, Erkan; Agildere, Ahmet Muhtesem [Baskent University Faculty of Medicine, Department of Radiology, Konya (Turkey)

    2015-05-01

    The aim of the study is to assess the effect of shape, diameter, elongation and deviation criteria of basilar artery (BA), convergence angle and diameter variations of vertebral arteries, and concurrent chronic diseases on posterior circulation infarcts. Between January 2010 and May 2013, 186 patients who underwent brain and diffusion magnetic resonance imaging (MRI) with suspected cerebrovascular accident and were diagnosed with posterior circulation infarct and 120 infarct negative control subjects were included in this case-control retrospective study. Vertebral artery (VA) and BA diameter, right (R) and left (L) VA angles at the level of bifurcation, and BA elongation-deviation, and shape of BA were assessed in a total of 306 subjects. Ischemic lesions in the posterior circulation were classified according to their anatomical location and vascular perfusion areas. No significant difference was noted between the control and patient groups with respect to BA diameter (p = 0.676). The most effective risk factors for posterior circulation infarcts were as follows: BA elongation of 2 or 3, BA transverse location of 2 or 3, increase in left VA angle, and history of hypertension, hypercholesterolemia, and diabetes mellitus. Our results suggest that prominent elongation and deviation, C and J shape of BA, and increased L VA angle may be the predictors of at-risk patients in posterior circulation infarcts. Reporting marked morphological BA and VA variations detected at routine brain MRI will aid in selection of patients. Timely detection and treatment of at-risk patients may be life-saving. (orig.)

  18. Predisposing factors in posterior circulation infarcts: a vascular morphological assessment

    International Nuclear Information System (INIS)

    The aim of the study is to assess the effect of shape, diameter, elongation and deviation criteria of basilar artery (BA), convergence angle and diameter variations of vertebral arteries, and concurrent chronic diseases on posterior circulation infarcts. Between January 2010 and May 2013, 186 patients who underwent brain and diffusion magnetic resonance imaging (MRI) with suspected cerebrovascular accident and were diagnosed with posterior circulation infarct and 120 infarct negative control subjects were included in this case-control retrospective study. Vertebral artery (VA) and BA diameter, right (R) and left (L) VA angles at the level of bifurcation, and BA elongation-deviation, and shape of BA were assessed in a total of 306 subjects. Ischemic lesions in the posterior circulation were classified according to their anatomical location and vascular perfusion areas. No significant difference was noted between the control and patient groups with respect to BA diameter (p = 0.676). The most effective risk factors for posterior circulation infarcts were as follows: BA elongation of 2 or 3, BA transverse location of 2 or 3, increase in left VA angle, and history of hypertension, hypercholesterolemia, and diabetes mellitus. Our results suggest that prominent elongation and deviation, C and J shape of BA, and increased L VA angle may be the predictors of at-risk patients in posterior circulation infarcts. Reporting marked morphological BA and VA variations detected at routine brain MRI will aid in selection of patients. Timely detection and treatment of at-risk patients may be life-saving. (orig.)

  19. Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts.

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    Lee, Kee-Won; Johnson, Noah R; Gao, Jin; Wang, Yadong

    2013-12-01

    Host cell recruitment is crucial for vascular graft remodeling and integration into the native blood vessel; it is especially important for cell-free strategies which rely on host remodeling. Controlled release of growth factors from vascular grafts may enhance host cell recruitment. Stromal cell-derived factor (SDF)-1α has been shown to induce host progenitor cell migration and recruitment; however, its potential in regenerative therapies is often limited due to its short half-life in vivo. This report describes a coacervate drug delivery system for enhancing progenitor cell recruitment into an elastomeric vascular graft by conferring protection of SDF-1α. Heparin and a synthetic polycation are used to form a coacervate, which is incorporated into poly(glycerol sebacate) (PGS) scaffolds. In addition to protecting SDF-1α, the coacervate facilitates uniform scaffold coating. Coacervate-laden scaffolds have high SDF-1α loading efficiency and provide sustained release under static and physiologically-relevant flow conditions with minimal initial burst release. In vitro assays showed that coacervate-laden scaffolds enhance migration and infiltration of human endothelial and mesenchymal progenitor cells by maintaining a stable SDF-1α gradient. These results suggest that SDF-1α coacervate-laden scaffolds show great promise for in situ vascular regeneration.

  20. It Is All in the Blood: The Multifaceted Contribution of Circulating Progenitor Cells in Diabetic Complications

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    Gian Paolo Fadini

    2012-01-01

    Full Text Available Diabetes mellitus (DM is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs along with excess smooth muscle progenitor (SMP and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.

  1. Effect of matrix composition on differentiation of nestin-positive neural progenitors from circulation into neurons

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    Jose, Anumol; Krishnan, Lissy K.

    2010-06-01

    The human peripheral blood mononuclear cell has a mixture of progenitor cells with potential to differentiate into a wide range of lineages. The ability of hematopoietic tissue-derived adult stem cells to differentiate into neural progenitor cells offers an alternative to embryonic stem cells as a viable source for cell transplantation therapies to cure neurodegenerative diseases. This approach could lead to the use of autologous progenitors from blood circulation; however, due to the limited numbers available, in vitro cell expansion may be indispensable. In addition, for successful transplantation there is the requirement of a delivery matrix on which cells can survive and differentiate. In this context we carried out this study to identify a suitable biodegradable matrix on which progenitor cells can home, multiply and differentiate. We designed different compositions of the biomimetic matrix containing fibrin, fibronectin, gelatin, growth factors, laminin and hyaluronic acid. The attached cells expressed proliferation markers in initial periods of culture and between days 6 and 9 in culture they differentiated into neurons and/or astrocytes. The differentiation of progenitors into neurons and asterocyte on the composed matrix was established by morphological and immunochemical analysis. Flow cytometric analysis of cells in culture was employed to track development of neurons which expressed an early marker β-tubulin3 and a terminal marker microtubule-associated protein-2 at a later culture period. In vitro experiments indicate that a highly specific niche consisting of various components of the extracellular matrix, including hyaluronic acid, promote cell homing, survival and differentiation.

  2. Circulating Endothelial Progenitor Cell and Platelet Microparticle Impact on Platelet Activation in Hypertension Associated with Hypercholesterolemia

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    Nicoleta Alexandru; Doina Popov; Emanuel Dragan; Eugen Andrei; Adriana Georgescu

    2013-01-01

    AIM: The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia. METHODS: Golden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) 'prevention', HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv) 'regression', HHfin-EPCs, HH treated with EPCs aft...

  3. Stepwise Optimization of the Procedure for Assessment of Circulating Progenitor Cells in Patients with Myocardial Infarction

    OpenAIRE

    Yu-Xin Cui; Tom Johnson; Andreas Baumbach; Reeves, Barnaby C.; Rogers, Chris A; Angelini, Gianni D; Debbie Marsden; Paolo Madeddu

    2012-01-01

    BACKGROUND: The number and functional activity of circulating progenitor cells (CPCs) is altered in diabetic patients. Furthermore, reduced CPC count has been shown to independently predict cardiovascular events. Validation of CPCs as a biomarker for cardiovascular risk stratification requires rigorous methodology. Before a standard operation protocol (SOP) can be designed for such a trial, a variety of technical issues have to be addressed fundamentally, which include the appropriate type of...

  4. CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

    NARCIS (Netherlands)

    Eman, Rhandy M; Hoorntje, Edgar T; Oner, F Cumhur; Kruyt, Moyo C; Dhert, Wouter J A; Alblas, Jacqueline

    2014-01-01

    Bone defect healing is highly dependent on the simultaneous stimulation of osteogenesis and vascularization. In bone regenerative strategies, combined seeding of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) proves their mutual stimulatory effects. Here, we investigated wh

  5. Human fetal aorta-derived vascular progenitor cells: identification and potential application in ischemic diseases

    OpenAIRE

    Invernici, Gloria; Madeddu, Paolo; Emanueli, Costanza; Parati, Eugenio A.; Alessandri, Giulio

    2008-01-01

    Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (i.e., angioblasts), is poorly understood. Here we report a summary of our recent studies on the identification of a population of vascular progenitor cells (VPCs) in human fetal aorta. These undifferentiated mesenchymal cells co-express endothelial and myogenic markers (CD133+, CD34+, KDR+, desmin+) and are localized in outer layer of the aortic stroma of 11–12 weeks old human fetu...

  6. Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers

    NARCIS (Netherlands)

    van Ark, J.; Moser, J.; Lexis, C. P. H.; Bekkema, F.; Pop, I.; van der Horst, I. C. C.; Zeebregts, C. J.; van Goor, H.; Wolffenbuttel, B. H. R.; Hillebrands, J. L.

    2012-01-01

    Individuals with type 2 diabetes mellitus have increased rates of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs) and smooth muscle progenitor cells (SMPCs) are suggested to play a role in the pathogenesis of MVD. The relationship between vasoreg

  7. Batroxobin mobilizes circulating endothelial progenitor cells in patients with deep vein thrombosis.

    Science.gov (United States)

    Lei Zhang; Shi Hong Lu; Li Li; Tao, Yu-Guo; Yong Ling Wan; Senga, Hirobumi; Renchi Yang; Zhong Chao Han

    2011-02-01

    Batroxobin, a thrombin-like enzyme from Bothrops atrox moojeni venom, is associated with the reduction of fibrinogen levels in plasma and the enhancement of anticoagulation and fibrinolysis. In this study, 15 patients with deep vein thrombosis (DVT) achieved successful limb salvage after the administration of batroxobin. We found that the levels of CD34+, CD31+, CD34+/CD31+, and vascular endothelial cadherin (VE-cadherin+) cells had increased in the peripheral blood of patients at 7 days and 14 days after treatment. At 0 day, 7 days, and 14 days, the percentages of CD34+ cells, which are assumed to be hematopoietic stem cells, are 0.39% ± 0.43%, 0.71% ± 0.50%, and 1.11% ± 0.66%, respectively. The levels of CD34+ cells at 14 days are significantly higher than the levels on the first day (P = .004). The levels of CD31+ cells and VE-cadherin+ cells, which represent mature endothelial cells, at 7 days (34.15% ± 11.32%, P = .013; 1.25% ± 1.39%, P = .014) and 14 days (35.21% ± 7.66%, P = .071; 1.85% ± 2.60%, P = .117) were slightly elevated compared with those at 0 day (27.55% ± 8.65%; 0.25 ± 0.39%). The double positive of CD34 and CD31 cells are assumed to be endothelial progenitor cells (EPCs). The levels of CD34+/CD31+ cells at 7 days (0.69% ± 0.50%, P = .001) and 14 days (1.07% ± 0.66%, P = .006) are significantly higher than that on the initial day (0.28% ± 0.30%). The number of CD34+/CD31+ cells significantly increased, indicating that in addition to its role in anticoagulation and fibrinolysis, treatment with batroxobin might simultaneously activate circulating EPCs that might promote the recanalization of the damaged vessel wall. PMID:19825915

  8. Circulating endothelial progenitor cells in traumatic brain injury: an emerging therapeutic target?

    Institute of Scientific and Technical Information of China (English)

    WEI Hui-jie; JIANG Rong-cai; LIU Li; ZHANG Jian-ning

    2010-01-01

    Traumatic brain injury (TBI) is a major cause ofmortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations.In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBl in the future.

  9. Circulating calcium concentrations, vascular disease and mortality: a systematic review.

    Science.gov (United States)

    Reid, I R; Gamble, G D; Bolland, M J

    2016-06-01

    Associations between serum calcium and vascular disease have been reported, but the consistency of these findings is unknown. We conducted a systematic review to determine whether circulating calcium concentrations are associated with risks of cardiovascular disease and death in normocalcaemic populations. We conducted PubMed searches up to 18 December 2014 and scrutinized reference lists of papers. Eligible studies related serum calcium to mortality or cardiovascular events in humans. A follow-up of at least one year was required for longitudinal studies. Studies in populations selected on the basis of renal disease or abnormal serum calcium were excluded. Two investigators performed independent data extraction. The results were tabulated and, where possible, meta-analysed. Five of 11 studies reported a statistically significant positive association between serum calcium and mortality. Meta-analysis of eight of these studies showed a hazard ratio of death of 1.13 (1.09, 1.18) per standard deviation of serum calcium. Eight of 13 studies reported a statistically significant positive association between serum calcium and cardiovascular disease. Meta-analysis of eight studies showed a hazard ratio of cardiovascular disease of 1.08 (1.04, 1.13) per standard deviation of serum calcium. For two studies reporting odds ratios, the pooled odds ratio per standard deviation was 1.22 (1.11, 1.32). When hazard ratios adjusted for cardiovascular risk factors were meta-analysed, the pooled hazard ratio was 1.04 (1.01, 1.08). Other studies demonstrated associations between serum calcium and stroke and between serum calcium and direct measurements of arterial disease and calcification. These observational data indicate that serum calcium is associated with vascular disease and death, but they cannot determine causality. PMID:26749423

  10. Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity.

    Directory of Open Access Journals (Sweden)

    Julia M Kröpfl

    Full Text Available A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15. The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI, cortisol (Co and interleukin-6 (IL-6. Additionally, the influence of exercise-induced NE and blood lactate (La on CPC functionality was analyzed in a randomly selected group of subjects (n = 6 in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.

  11. Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

    Science.gov (United States)

    Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

    2015-12-01

    Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue.

  12. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Gemma Chiva-Blanch

    Full Text Available Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger

  13. Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.

    Science.gov (United States)

    Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Kajimura, Junko; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

    2016-01-01

    It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels. PMID:26720799

  14. Deficit of circulating stem – progenitor cells in opiate addiction: a pilot study

    Directory of Open Access Journals (Sweden)

    Davidson Peter

    2007-07-01

    Full Text Available Abstract A substantial literature describes the capacity of all addictive drugs to slow cell growth and potentiate apoptosis. Flow cytometry was used as a means to compare two lineages of circulating progenitor cells in addicted patients. Buprenorphine treated opiate addicts were compared with medical patients. Peripheral venous blood CD34+ CD45+ double positive cells were counted as haemopoietic stem cells (HSC's, and CD34+ KDR+ (VEGFR2+ cells were taken as endothelial progenitor cells (EPC's. 10 opiate dependent patients with substance use disorder (SUD and 11 non-addicted (N-SUD were studied. The ages were (mean + S.D. 36.2 + 8.6 and 56.4 + 18.6 respectively (P 0.15, OR = 0.09, 95% C.I. 0.01–0.97, a finding of some interest given the substantially older age of the N-SUD group. These laboratory data are thus consistent with clinical data suggesting accelerated ageing in addicted humans and implicate the important stem cell pool in both addiction toxicology and ageing. They carry important policy implications for understanding the fundamental toxicology of addiction, and suggest that the toxicity both of addiction itself and of indefinite agonist maintenance therapies may have been seriously underestimated.

  15. Lipid lowering and HDL raising gene transfer increase endothelial progenitor cells, enhance myocardial vascularity, and improve diastolic function.

    Directory of Open Access Journals (Sweden)

    Stephanie C Gordts

    Full Text Available BACKGROUND: Hypercholesterolemia and low high density lipoprotein (HDL cholesterol contribute to coronary heart disease but little is known about their direct effects on myocardial function. Low HDL and raised non-HDL cholesterol levels carried increased risk for heart failure development in the Framingham study, independent of any association with myocardial infarction. The objective of this study was to test the hypothesis that increased endothelial progenitor cell (EPC number and function after lipid lowering or HDL raising gene transfer in C57BL/6 low density lipoprotein receptor deficient (LDLr(-/- mice may be associated with an enhanced relative vascularity in the myocardium and an improved cardiac function. METHODOLOGY/PRINCIPAL FINDINGS: Lipid lowering and HDL raising gene transfer were performed using the E1E3E4-deleted LDLr expressing adenoviral vector AdLDLr and the human apolipoprotein A-I expressing vector AdA-I, respectively. AdLDLr transfer in C57BL/6 LDLr(-/- mice resulted in a 2.0-fold (p<0.05 increase of the circulating number of EPCs and in an improvement of EPC function as assessed by ex vivo EPC migration and EPC adhesion. Capillary density and relative vascularity in the myocardium were 28% (p<0.01 and 22% (p<0.05 higher, respectively, in AdLDLr mice compared to control mice. The peak rate of isovolumetric relaxation was increased by 12% (p<0.05 and the time constant of isovolumetric relaxation was decreased by 14% (p<0.05 after AdLDLr transfer. Similarly, HDL raising gene transfer increased EPC number and function and raised both capillary density and relative vascularity in the myocardium by 24% (p<0.05. The peak rate of isovolumetric relaxation was increased by 16% (p<0.05 in AdA-I mice compared to control mice. CONCLUSIONS/SIGNIFICANCE: Both lipid lowering and HDL raising gene transfer have beneficial effects on EPC biology, relative myocardial vascularity, and diastolic function. These findings raise concerns over the

  16. Homing of circulating blood endothelial progenitor cells after myocardial infarction is mediated by Akt-SDF-1-signal pathway

    Institute of Scientific and Technical Information of China (English)

    赵岚

    2013-01-01

    Objective To investigate the expressions of protein kinase B(Akt) and stromal cell-derived factor-1(SDF-1) and their relations with circulating blood endothelial progenitor cell homing after myocardial infarction(MI). Methods MI was induced in the

  17. Role of Endothelin in Uteroplacental Circulation and Fetal Vascular Function

    OpenAIRE

    Paradis, Alexandra; Zhang, Lubo

    2013-01-01

    Endothelins are 21-amino acid peptides involved in vascular homeostasis. Three types of peptide have been identified, with endothelin-1 (ET-1) being the most potent vasoconstrictor currently known. Two endothelin receptor sub-types are found in various tissues, including the brain, heart, blood vessel, lung, and placenta. The ETA-receptor is associated with vasoconstriction in vascular smooth muscle. Conversely, the ETB-receptor can elicit a vasoconstrictor effect in vascular smooth muscle an...

  18. Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

    Directory of Open Access Journals (Sweden)

    Tsai Tzu-Hsien

    2012-07-01

    Full Text Available Abstract Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs and left ventricular ejection fraction (LVEF. Methods High fat diet (45 Kcal% fat was given to 8-week-old C57BL/6 J mice (n = 8 for 20 weeks to induce obesity (group 1. Another age-matched group (n = 8 were fed with control diet for 20 weeks as controls (group 2. The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling.

  19. Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

    Science.gov (United States)

    Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

    2011-04-01

    Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects.

  20. Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

    Science.gov (United States)

    Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

    2011-04-01

    Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects. PMID:20494372

  1. Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle like cells and form vascular networks in vivo.

    Science.gov (United States)

    Ferreira, Lino S; Gerecht, Sharon; Shieh, Hester F; Watson, Nicki; Rupnick, Maria A; Dallabrida, Susan M; Vunjak-Novakovic, Gordana; Langer, Robert

    2007-08-01

    We report that human embryonic stem cells contain a population of vascular progenitor cells that have the ability to differentiate into endothelial-like and smooth muscle (SM)-like cells. Vascular progenitor cells were isolated from EBs grown in suspension for 10 days and were characterized by expression of the endothelial/hematopoietic marker CD34 (CD34+ cells). When these cells are subsequently cultured in EGM-2 (endothelial growth medium) supplemented with vascular endothelial growth factor-165 (50 ng/mL), they give rise to endothelial-like cells characterized by a cobblestone cell morphology, expression of endothelial markers (platelet endothelial cell-adhesion molecule-1, CD34, KDR/Flk-1, vascular endothelial cadherin, von Willebrand factor), incorporation of acetylated low-density lipoprotein, and formation of capillary-like structures when placed in Matrigel. In contrast, when CD34+ cells are cultured in EGM-2 supplemented with platelet-derived growth factor-BB (50 ng/mL), they give rise to SM-like cells characterized by spindle-shape morphology, expression of SM cell markers (alpha-SM actin, SM myosin heavy chain, calponin, caldesmon, SM alpha-22), and the ability to contract and relax in response to common pharmacological agents such as carbachol and atropine but rarely form capillary-like structures when placed in Matrigel. Implantation studies in nude mice show that both cell types contribute to the formation of human microvasculature. Some microvessels contained mouse blood cells, which indicates functional integration with host vasculature. Therefore, the vascular progenitors isolated from human embryonic stem cells using methods established in the present study could provide a means to examine the mechanisms of endothelial and SM cell development, and they could also provide a potential source of cells for vascular tissue engineering.

  2. Circulating endothelial progenitor cell and platelet microparticle impact on platelet activation in hypertension associated with hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Nicoleta Alexandru

    Full Text Available AIM: The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs and platelet microparticles (PMPs on blood platelet function in experimental hypertension associated with hypercholesterolemia. METHODS: Golden Syrian hamsters were divided in six groups: (i control, C; (ii hypertensive-hypercholesterolemic, HH; (iii 'prevention', HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv 'regression', HHfin-EPCs, HH treated with EPCs after HH feeding; (v HH treated with PMPs, HH-PMPs, and (vi HH treated with EPCs and PMPs, HH-EPCs-PMPs. RESULTS: Compared to HH group, the platelets from HHin-EPCs and HHfin-EPCs groups showed a reduction of: (i activation, reflected by decreased integrin 3β, FAK, PI3K, src protein expression; (ii secreted molecules as: SDF-1, MCP-1, RANTES, VEGF, PF4, PDGF and (iii expression of pro-inflammatory molecules as: SDF-1, MCP-1, RANTES, IL-6, IL-1β; TFPI secretion was increased. Compared to HH group, platelets of HH-PMPs group showed increased activation, molecules release and proteins expression. Compared to HH-PMPs group the combination EPCs with PMPs treatment induced a decrease of all investigated platelet molecules, however not comparable with that recorded when EPC individual treatment was applied. CONCLUSION: EPCs have the ability to reduce platelet activation and to modulate their pro-inflammatory and anti-thrombogenic properties in hypertension associated with hypercholesterolemia. Although, PMPs have several beneficial effects in combination with EPCs, these did not improve the EPC effects. These findings reveal a new biological role of circulating EPCs in platelet function regulation, and may contribute to understand their cross talk, and the mechanisms of atherosclerosis.

  3. Prognostic relevance of circulating endothelial progenitor cells in patients with chronic heart failure.

    Science.gov (United States)

    Koller, Lorenz; Hohensinner, Philipp; Sulzgruber, Patrick; Blum, Steffen; Maurer, Gerald; Wojta, Johann; Hülsmann, Martin; Niessner, Alexander

    2016-08-01

    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; pHR 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. PMID:27412580

  4. Changes of circulating progenitor cells and circulating endothelial progenitor cells in patients With sepsis%脓毒症患者外周血祖细胞和内皮祖细胞数量的变化

    Institute of Scientific and Technical Information of China (English)

    童朝阳; 宋振举; 姚晨玲; 邵勉; 黄培志

    2009-01-01

    目的 检测脓毒症患者外周血单个核细胞(peripheral blood mononuelear cell,PBMC)中祖细胞和血管内皮祖细胞(endothelial progenitor cells,EPC)相对数量的变化,探讨感染性休克和非休克患者外周血EPC变化的特点.方法 收集2007年8月至2008年2月复大学附属中山医院急诊科收治的脓毒症患者27例进行前瞻性研究,其中感染性休克患者12例、非休克患者15例,另选10例健康成年人作为正常对照,ICU非脓毒症患者10例作为ICU对照.Ficoll梯度离心法分离外周血PBMC,通过流式细胞仪检测外周血PBMC标记的CDl33,CIY34和血管内皮牛长因子受体-2(vascular endothelialgrowth factor receptor-2.VEGFR-2)的表达情况,计算祖细胞以及内皮祖细胞的相对数量.组间比较采用单因素方差分析.结果 健康成年人外周血祖细胞、EPC数量较少,分别占PBMC的0.25%.4-0.14%和0.09%.4-0.02%;ICU非脓毒症患者祖细胞和EPC数量分别占PBMC的0.38%.4-0.29%和0.12%.4-O.02%,与正常对照组相比无明显的变化(P>0.05);脓毒症非休克组患者外周血祖细胞、EPC的数量明显增加,分别占PBMC的0.57%±0.12%和0.22%±0.10%,与正常对照组相比差异具有统计学意义(P<0.05);感染性休克患者外周血祖细胞和EPE的数量明显减少,分别占PBMC的0.20%.4-0.12%和0.04%±O.01%,与非休克组、ICU对照组和正常对照组相比差异均具有统计学意义(Pcirculaling progenitor cells and endothelial progenitor cells(EPCs)in non-septic and septic shock patients using flow cytometry.Method A total of 27 sepsis patients hospitalized in emergency

  5. Decreased Number of Circulating Endothelial Progenitor Cells (CD133+/KDR+) in Patients with Psoriatic Arthritis.

    Science.gov (United States)

    Batycka-Baran, Aleksandra; Paprocka, Maria; Baran, Wojciech; Szepietowski, Jacek C

    2016-08-23

    Cardiovascular diseases are a major cause of mortality in patients with psoriatic arthritis (PsA), but the precise mechanism of increased cardiovascular risk is unknown. Endothelial dysfunction plays a crucial role in the development of atherosclerosis. Circulating endothelial progenitor cells (CEPCs) contribute to endothelial regeneration and their level may be affected by chronic inflammation. The aim of this study was to evaluate the number of CEPCs in patients with PsA (n = 24) compared with controls (n = 26). CEPCs were identified as CD133+/ KDR+ cells in peripheral blood, using flow cytometry. A significantly decreased number of CEPCs was observed in patients with PsA (p number of these cells was significantly, inversely correlated with the severity of skin and joint involvement (Psoriasis Area and Severity Index (PASI), DAS28) and the level of C-reactive protein. We hypothesize that the reduced number of CEPCs may indicate and contribute to the increased cardiovascular risk in patients with PsA.

  6. Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity.

    Science.gov (United States)

    Kröpfl, Julia M; Stelzer, Ingeborg; Mangge, Harald; Pekovits, Karin; Fuchs, Robert; Allard, Nathalie; Schinagl, Lukas; Hofmann, Peter; Dohr, Gottfried; Wallner-Liebmann, Sandra; Domej, Wolfgang; Müller, Wolfram

    2014-01-01

    A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality. PMID:25180783

  7. Circulating hyaluronate: concentration in different vascular beds in man

    DEFF Research Database (Denmark)

    Bentsen, K D; Henriksen, Jens Henrik Sahl; Laurent, T C

    1986-01-01

    The plasma concentration of hyaluronate (hyaluronic acid; HA) was measured in different vascular beds in order to determine regional kinetics of endogenous HA in fasting, supine subjects with normal (n = 6) or moderately decreased kidney function (n = 9). In both groups hepatic venous HA was...

  8. Number and function of peripheral blood endothelial progenitor cells in Henoch-Schönlein purpura nephritis children with different degrees of renal vascular lesions

    OpenAIRE

    DANG, XI-QIANG; HE, XIAO-JIE; CHEN, HAI-XIA; HE, QING-NAN; Yi, Zhu-Wen

    2012-01-01

    The aim of this study was to explore the correlation between different degrees of renal vascular lesions in children with Henoch-Schönlein purpura nephritis (HSPN) and changes in progenitor cell number and function in peripheral blood. Forty-eight HSPN patients were divided into three groups, mild, moderate and severe, according to the degree of renal vascular lesions. Peripheral blood mononuclear cells were isolated and cultured. Endothelial progenitor cells (EPCs) were identified by immunof...

  9. Trichostatin A enhances vascular repair by injected human endothelial progenitors through increasing the expression of TAL1-dependent genes.

    Science.gov (United States)

    Palii, Carmen G; Vulesevic, Branka; Fraineau, Sylvain; Pranckeviciene, Erinija; Griffith, Alexander J; Chu, Alphonse; Faralli, Hervé; Li, Yuhua; McNeill, Brian; Sun, Jie; Perkins, Theodore J; Dilworth, F Jeffrey; Perez-Iratxeta, Carol; Suuronen, Erik J; Allan, David S; Brand, Marjorie

    2014-05-01

    A major goal of cell therapy for vascular diseases is to promote revascularization through the injection of endothelial stem/progenitor cells. The gene regulatory mechanisms that underlie endothelial progenitor-mediated vascular repair, however, remain elusive. Here, we identify the transcription factor TAL1/SCL as a key mediator of the vascular repair function of primary human endothelial colony-forming cells (ECFCs). Genome-wide analyses in ECFCs demonstrate that TAL1 activates a transcriptional program that promotes cell adhesion and migration. At the mechanistic level, we show that TAL1 upregulates the expression of migratory and adhesion genes through recruitment of the histone acetyltransferase p300. Based on these findings, we establish a strategy that enhances the revascularization efficiency of ECFCs after ischemia through ex vivo priming with the histone deacetylase inhibitor TSA. Thus, small molecule epigenetics drugs are effective tools for modifying the epigenome of stem/progenitor cells prior to transplantation as a means to enhance their therapeutic potential. PMID:24792117

  10. Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker

    OpenAIRE

    Tatjana M H Niers; Richel, Dick J.; Meijers, Joost C.M.; Schlingemann, Reinier O.

    2011-01-01

    BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. METHODOLOGY: We determined VEGF levels in PECT, a medi...

  11. Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial.

    Science.gov (United States)

    Jeong, Han Saem; Kim, Sohyeon; Hong, Soon Jun; Choi, Seung Cheol; Choi, Ji-Hyun; Kim, Jong-Ho; Park, Chi-Yeon; Cho, Jae Young; Lee, Tae-Bum; Kwon, Ji-Wung; Joo, Hyung Joon; Park, Jae Hyoung; Yu, Cheol Woong; Lim, Do-Sun

    2016-04-01

    Administration of black raspberry (Rubus occidentalis) is known to improve vascular endothelial function in patients at a high risk for cardiovascular (CV) disease. We investigated short-term effects of black raspberry on circulating endothelial progenitor cells (EPCs) and arterial stiffness in patients with metabolic syndrome. Patients with metabolic syndrome (n = 51) were prospectively randomized into the black raspberry group (n = 26, 750 mg/day) and placebo group (n = 25) during the 12-week follow-up. Central blood pressure, augmentation index, and EPCs, such as CD34/KDR(+), CD34/CD117(+), and CD34/CD133(+), were measured at baseline and at 12-week follow-up. Radial augmentation indexes were significantly decreased in the black raspberry group compared to the placebo group (-5% ± 10% vs. 3% ± 14%, P raspberry group compared to the placebo group (19 ± 109/μL vs. -28 ± 57/μL, P raspberry group compared to the placebo group (-0.5 ± 1.4 pg/mL vs. -0.1 ± 1.1 pg/mL, P raspberry group. The use of black raspberry significantly lowered the augmentation index and increased circulating EPCs, thereby improving CV risks in patients with metabolic syndrome during the 12-week follow-up.

  12. Rosiglitazone promotes development of a novel adipocyte population from bone marrow–derived circulating progenitor cells

    OpenAIRE

    Crossno, Joseph T.; Majka, Susan M.; Grazia, Todd; Gill, Ronald G.; Klemm, Dwight J.

    2006-01-01

    Obesity and weight gain are characterized by increased adipose tissue mass due to an increase in the size of individual adipocytes and the generation of new adipocytes. New adipocytes are believed to arise from resident adipose tissue preadipocytes and mesenchymal progenitor cells. However, it is possible that progenitor cells from other tissues, in particular BM, could also contribute to development of new adipocytes in adipose tissue. We tested this hypothesis by transplanting whole BM cell...

  13. Quantification of circulating endothelial progenitor cells using the modified ISHAGE protocol.

    Directory of Open Access Journals (Sweden)

    Caroline Schmidt-Lucke

    Full Text Available AIMS: Circulating endothelial progenitor cells (EPC, involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data. METHODS AND RESULTS: In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS, EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45(dimCD34(+ cells were quantified for KDR. A minimum of 100 CD34(+ events were collected. For comparison, CD45(+CD34(+ and CD45(-CD34(+ were analysed simultaneously. The number of CD45(dimCD34(+KDR(+ cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend. An inverse correlation of CD45(dimCD34(+KDR(+ with disease activity (r = -0.475, p<0.001 was confirmed. Only CD45(dimCD34(+KDR(+ correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005. In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45(dimCD34(+KDR(+ EPC (p<0.05. CD45(+CD34(+KDR(+ and CD45(-CD34(+KDR(+ were indifferent between the three groups. CONCLUSION: Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in

  14. Circulation, bone scans, and tetracycline labeling in microvascularized and vascular bundle implanted rib grafts

    International Nuclear Information System (INIS)

    The circulation in microvascularized rib grafts has been compared with that in conventional rib grafts and in those augmented by a direct vascular bundle implantation into the bone grafts. A new experimental model has been designed to correlate vascular perfusion, bone scan patterns, tetracycline labeling, and histological findings in these bone grafts. Posterior microvascularized rib grafts were found to have a circulatory pattern identical to that of the normal rib. Failed microvascularized rib grafts were revascularized more slowly than conventional rib grafts. Vascular bundles implanted into rib grafts remained patent and increased the rate of revascularization. The stripping or preservation of periosteum had no observable effects on the rate or pattern of conventional rib graft revascularization. The circulation in rib grafts was accurately reflected in technetium 99 bone scans, as was the patency of the anastomoses of microvascularized rib grafts and of implanted vascular bundles. In contrast, tetracycline labeling was repeatedly observed in avascular areas of bone grafts and, therefore, is not a reliable indicator of bone graft circulation

  15. Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development

    Science.gov (United States)

    Holoyda, Kathleen A.; Hou, Xiaogang; Fowler, Kathryn L.; Grikscheit, Tracy C.

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Methods VEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration. Results Increased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2. Conclusions Manipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future

  16. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function.

    Directory of Open Access Journals (Sweden)

    Maria Tikhonenko

    Full Text Available OBJECTIVE: The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs. We propose that n-3 polyunsaturated fatty acid (PUFA deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs. RESEARCH DESIGN AND METHODS: Type 2 diabetic rats on control or docosahexaenoic acid (DHA-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL-1β, IL-6, intracellular adhesion molecule (ICAM-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined. RESULTS: DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation. CONCLUSIONS: In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function.

  17. Adiponectin levels are associated with the number and activity of circulating endothelial progenitor cells in patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang YING; Dan-dan ZHONG; Geng XU; Miao-yan CHEN; Qing-yu CHEN

    2009-01-01

    Objective: To study the relationship between plasma adiponectin concentration and the functional activities of circulating endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). Methods: Circulating EPCs were enumerated as AC133+/KDR+ cells via flow cytometry and identified by co-staining with Dii-acLDL and fluorescein isothiocy-anate (FITC)-conjugated lectin under a fluorescent microscope. The migratory capacity of EPCs was measured by modified Boyden chamber assay. Adhesion capacity was performed to count adherent cells after replating EPCs on six-well culture dishes coated with fibronectin. Results: The number of circulating EPCs (AC133+/KDR+ cells) decreased significantly in CAD patients, compared with control subjects [(74.2±12.3) vs (83.5±12.9) cells/ml blood, P<0.0\\]. In addition, the number of EPCs also decreased in CAD patients after ex vivo cultivation [(54.4±8.6) vs (71.9±11.6) EPCs/field, P<0.01]. Both circulating EPCs and differentiated EPCs were positively correlated with plasma adiponectin concentration. The functional activities of EPCs from CAD patients, such as migratory and adherent capacities, were also impaired, compared with control subjects, and positively correlated with plasma adiponectin concentration. Conclusion: The study demonstrates that the impairment of the number and functional activities of EPCs in CAD patients is correlated with their lower plasma adiponectin concentrations.

  18. Cilostazol Enhances Mobilization of Circulating Endothelial Progenitor Cells and Improves Endothelium-Dependent Function in Patients at High Risk of Cardiovascular Disease.

    Science.gov (United States)

    Chao, Ting-Hsing; Chen, I-Chih; Lee, Cheng-Han; Chen, Ju-Yi; Tsai, Wei-Chuan; Li, Yi-Heng; Tseng, Shih-Ya; Tsai, Liang-Miin; Tseng, Wei-Kung

    2016-08-01

    This is the first study to investigate the vasculoangiogenic effects of cilostazol on endothelial progenitor cells (EPCs) and flow-mediated dilatation (FMD) in patients at high risk of cardiovascular disease (CVD). This double-blind, placebo-controlled study included 71 patients (37 received 200 mg/d cilostazol and 34 received placebo for 12 weeks). Use of cilostazol, but not placebo, significantly increased circulating EPC (kinase insert domain receptor(+)CD34(+)) counts (percentage changes: 149.0% [67.9%-497.8%] vs 71.9% [-31.8% to 236.5%], P = .024) and improved triglyceride and high-density lipoprotein cholesterol levels (P = .002 and P = .003, respectively). Plasma levels of vascular endothelial growth factor (VEGF)-A165 and FMD significantly increased (72.5% [32.9%-120.4%] vs -5.8% [-46.0% to 57.6%], P = .001; 232.8% ± 83.1% vs -46.9% ± 21.5%, P = .003, respectively) in cilostazol-treated patients. Changes in the plasma triglyceride levels significantly inversely correlated with the changes in the VEGF-A165 levels and FMD. Cilostazol significantly enhanced the mobilization of EPCs and improved endothelium-dependent function by modifying some metabolic and angiogenic markers in patients at high risk of CVD. PMID:27401788

  19. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Lipsic, Erik; van der Meer, Peter; van der Harst, Pirn; Oeseburg, Hisko; Sarvaas, Gideon J. Du Marchie; Koster, Johan; Voors, Adriaan A.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Schoemaker, Regien G.

    2007-01-01

    Aims Erythropoietin (EPO) improves cardiac function and induces neovascutarization in chronic heart failure (CHF), although the exact mechanism has not been elucidated. We studied the effects of EPO on homing and incorporation of endothelial progenitor cells (EPC) into the myocardial microvasculatur

  20. Late Release of Circulating Endothelial Cells and Endothelial Progenitor Cells after Chemotherapy Predicts Response and Survival in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jeanine M. Roodhart

    2010-01-01

    Full Text Available We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor cells (CE(PCs and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS. Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(PC by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(PCs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(PCs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(PC was found (P < .01, independent of the type of chemotherapy. Changes in CE(PC levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(PC is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.

  1. Circulating vascular endothelial growth factor six months after primary surgery as a prognostic marker in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Werther, Kim; Sørensen, Steen; Christensen, Ib Jarle;

    2003-01-01

    High preoperative circulating vascular endothelial growth factor (VEGF) is predictive of poor prognosis in patients with colorectal cancer (CRC). However, postoperative circulating VEGF has not yet been evaluated as a prognostic marker in CRC patients. In 318 consecutive patients who had undergone...

  2. Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

    Directory of Open Access Journals (Sweden)

    Chen Yung-Lung

    2012-07-01

    Full Text Available Abstract Background and aim We tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs, angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control. Methods 8-week-old C57BL/6J mice (n = 27 were equally divided into group 1 (fed with 22-week control diet, group 2 (22-week high fat diet, and group 3 (14-week high fat diet, followed by 8-week control diet. Critical limb ischemia (CLI was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks. Results Heart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p  Conclusion Obesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.

  3. Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice

    DEFF Research Database (Denmark)

    Bentzon, Jacob Fog; Weile, Charlotte; Sondergaard, Claus S;

    2006-01-01

    Recent studies of bone marrow (BM)-transplanted apoE knockout (apoE-/-) mice have concluded that a substantial fraction of smooth muscle cells (SMCs) in atherosclerosis arise from circulating progenitor cells of hematopoietic origin. This pathway, however, remains controversial. In the present st...

  4. Acute Changes in Peripheral Vascular Tonus and Systemic Circulation during Static Stretching.

    Science.gov (United States)

    Inami, Takayuki; Baba, Reizo; Nakagaki, Akemi; Shimizu, Takuya

    2015-01-01

    This study aimed to investigate the acute effect of static stretching (SS) on peripheral vascular tonus and to clarify the effect of SS on systemic circulation. Twenty healthy young male volunteers performed a 1-min SS motion of the right triceps surae muscle, repeated five times. The peripheral vascular tonus (|d/a| ratio) was obtained using second derivatives of the photoplethysmogram readings before, during, and after SS. Heart rate and blood pressure (BP) were also measured. The |d/a| ratio and BP were transiently, but significantly, elevated during SS and returned to baseline immediately after SS. Furthermore, we observed a significant correlation between the amount of change in the |d/a| ratio and the ankle range of motion during SS (r = 0.793 to 0.832, P = 0.01). These responses may be caused by mechanical stress during SS. PMID:25833293

  5. YAP is oppositely regulated in iPSC-induced cardiovascular progenitor cell and vascular smooth muscle cell differentiation

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-yu; FAN Xiao-fang; DING Lu; CHEN Dan-yang; ZHAO Ru; LI Lan; GONG Yong-sheng

    2016-01-01

    AIM:To explore whether YAP protein is important in induced pluripotent stem cell ( iPSC)-induced cardiovascular progenitor cell and/or vascular smooth muscle differentiation .METHODS:Using episomal vector based reprogramming , we generated human iPSCs from donor fibroblasts .We used both this iPSCs and human H 1 embryonic stem cells to differentiate into vascular smooth muscle cells (VSMCs) through cardiovascular progenitor cells (CVPC).Western blotting, qPCR and immunofluorescence microscopy were used to check the expression of YAP and related genes during this differentiation process .RESULTS:The results showed that iPSCs expressed pluripotent stem cell markers, such as Oct4, Nanog, Sox2, TRA-1-60 and SSEA3, and could form teratoma in SCID mice.YAP was highly expressed in pluripotent stem cells , but dramatically decreased when CVPC differentiation started .YAP gradually increased dur-ing CVPC three-day differentiation.The TAZ and YAP binding partner TEAD1, but not TEAD2 and TEAD4, have similar expression pattern in CVPC differentiation .Immunofluorescence result confirmed that YAP was activated and accumulated in nucleus .Interesting-ly, both YAP and phosphorylated YAP expression decreased to very low level after CVPC differentiated into VSMCs in 7 days.TEAD4 and TAZ also decreased, while TEAD1, TEAD2 and TEAD3 expression did not change during VSMC differentiation .CONCLU-SION:YAP and TEAD1 expression increased during CVPC differentiation , while YAP and TEAD4 expression decreased from CVPC to VSMCs differentiation , which suggested YAP might have different function during diverse cell differentiation .

  6. Histamine receptors expressed in circulating progenitor cells have reciprocal actions in ligation-induced arteriosclerosis.

    Science.gov (United States)

    Yamada, Sohsuke; Wang, Ke-Yong; Tanimoto, Akihide; Guo, Xin; Nabeshima, Atsunori; Watanabe, Takeshi; Sasaguri, Yasuyuki

    2013-09-01

    Histamine is synthesized as a low-molecular-weight amine from L-histidine by histidine decarboxylase (HDC). Recently, we demonstrated that carotid artery-ligated HDC gene-deficient mice (HDC(-/-)) showed less neointimal formation than wild-type (WT) mice, indicating that histamine participates in the process of arteriosclerosis. However, little is known about the roles of histamine-specific receptors (HHRs) in arteriosclerosis. To define the roles of HHRs in arteriosclerosis, we investigated intimal remodeling in ligated carotid arteries of HHR-deficient mice (H1R(-/-) or H2R(-/-)). Quantitative analysis showed that H1R(-/-) mice had significantly less arteriosclerogenesis, whereas H2R(-/-) mice had more, as compared with WT mice. Bone marrow transplantation from H1R(-/-) or H2R(-/-) to WT mice confirmed the above observation. Furthermore, the increased expression of monocyte chemoattractant protein (MCP-1), platelet-derived growth factor (PDGF), adhesion molecules and liver X receptor (LXR)-related inflammatory signaling factors, including Toll-like receptor (TLR3), interleukin-1 receptor (IL-1R) and tumor necrosis factor receptor (TNF-R), was consistent with the arteriosclerotic phenotype of H2R(-/-) mice. Peripheral progenitor cells in H2R(-/-) mice accelerate ligation-induced arteriosclerosis through their regulation of MCP-1, PDGF, adhesion molecules and LXR-related inflammatory signaling factors. In contrast, peripheral progenitor cells act to suppress arteriosclerosis in H1R(-/-) mice, indicating that HHRs reciprocally regulate inflammation in the ligation-induced arteriosclerosis.

  7. Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.

    Science.gov (United States)

    Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

    2016-05-01

    Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34+Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. PMID:27169377

  8. Variations of circulating endothelial progenitor cells and transforming growth factor-beta-1 (TGF-β1) during thoracic radiotherapy are predictive for radiation pneumonitis

    International Nuclear Information System (INIS)

    The vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP). This study investigated the variations of circulating endothelial progenitor cells (EPCs) and transforming growth factor-beta-1 (TGF-β1) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non–small-cell lung cancer (NSCLC) and analyzed the correlation between these variations with the occurrence of RP. From November 2008 to November 2009, eighty-four consecutive patients receiving 3D-CRT for stage III disease were evaluated prospectively. Circulating EPCs and TGF-β1 levels were measured at baseline, every 2 weeks during, and at the end of treatment. RP was evaluated prospectively at 6 weeks after 3D-CRT. Thirty-eight patients (47.5%) experienced score 1 or more of RP. The baseline levels of EPCs and TGF-β1 were analyzed, no difference was found between patients with and without RP during and after 3D-CRT. By serial measurement of TGF-β1 and EPCs levels, we found that the mean levels of EPCs in the whole population remained stable during radiotherapy, but the mean levels of TGF-β1 increased slowly during radiotherapy. TGF-β1 and EPCs levels were all significantly higher at week 2, week 4 and week 6 in patients with RP than that in patients without RP, respectively. During the period of radiation treatment, TGF-β1 levels began to increase in the first 2 weeks and became significantly higher at week 6 (P < 0.01). EPCs levels also began to increase in the first 2 weeks and reached a peak at week 4. Using an ANOVA model for repeated-measures, we found significant associations between the levels of TGF-β1 and EPCs during the course of 3D-CRT and the risk of developing RP (P < 0.01). Most of the dosimetric factors showed a significant association with RP. Early variations of TGF-β1 and EPCs levels during 3D-CRT are significantly associated with the risk of RP. Variations of circulating TGF-β1

  9. Lung-homing of endothelial progenitor cells and airway vascularization is only partially dependant on eosinophils in a house dust mite-exposed mouse model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nirooya Sivapalan

    Full Text Available Asthmatic responses involve a systemic component where activation of the bone marrow leads to mobilization and lung-homing of progenitor cells. This traffic may be driven by stromal cell derived factor-1 (SDF-1, a potent progenitor chemoattractant. We have previously shown that airway angiogenesis, an early remodeling event, can be inhibited by preventing the migration of endothelial progenitor cells (EPC to the lungs. Given intranasally, AMD3100, a CXCR4 antagonist that inhibits SDF-1 mediated effects, attenuated allergen-induced lung-homing of EPC, vascularization of pulmonary tissue, airway eosinophilia and development of airway hyperresponsiveness. Since SDF-1 is also an eosinophil chemoattractant, we investigated, using a transgenic eosinophil deficient mouse strain (PHIL whether EPC lung accumulation and lung vascularization in allergic airway responses is dependent on eosinophilic inflammation.Wild-type (WT BALB/c and eosinophil deficient (PHIL mice were sensitized to house dust mite (HDM using a chronic exposure protocol and treated with AMD3100 to modulate SDF-1 stimulated progenitor traffic. Following HDM challenge, lung-extracted EPCs were enumerated along with airway inflammation, microvessel density (MVD and airway methacholine responsiveness (AHR.Following Ag sensitization, both WT and PHIL mice exhibited HDM-induced increase in airway inflammation, EPC lung-accumulation, lung angiogenesis and AHR. Treatment with AMD3100 significantly attenuated outcome measures in both groups of mice. Significantly lower levels of EPC and a trend for lower vascularization were detected in PHIL versus WT mice.This study shows that while allergen-induced lung-homing of endothelial progenitor cells, increased tissue vascularization and development lung dysfunction can occur in the absence of eosinophils, the presence of these cells worsens the pathology of the allergic response.

  10. Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Luciana Teofili

    2015-05-01

    Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

  11. Circulating endothelial progenitor cells do not contribute to regeneration of endothelium after murine arterial injury

    DEFF Research Database (Denmark)

    Hagensen, Mette; Raarup, Merete Krog; Mortensen, Martin Bødtker;

    2012-01-01

    into endothelial cells (ECs). We tested this theory in a murine arterial injury model using carotid artery transplants and fluorescent reporter mice. METHODS AND RESULTS: Wire-injured carotid artery segments from wild-type mice were transplanted into TIE2-GFP transgenic mice expressing green fluorescent protein...... (GFP) in ECs. We found that the endothelium regenerated with GFP(+) ECs as a function of time, evolving from the anastomosis sites towards the centre of the transplant. A migration front of ECs at Day 7 was verified by scanning electron microscopy and by bright-field microscopy using recipient TIE2-lac......Z mice with endothelial β-galactosidase expression. These experiments indicated migration of flanking ECs rather than homing of circulating cells as the underlying mechanism. To confirm this, we interposed non-injured wild-type carotid artery segments between the denuded transplant and the TIE2-GFP...

  12. Circulating endothelial progenitor cells: a new approach to anti-aging medicine?

    Directory of Open Access Journals (Sweden)

    Patel Amit N

    2009-12-01

    Full Text Available Abstract Endothelial dysfunction is associated with major causes of morbidity and mortality, as well as numerous age-related conditions. The possibility of preserving or even rejuvenating endothelial function offers a potent means of preventing/treating some of the most fearful aspects of aging such as loss of mental, cardiovascular, and sexual function. Endothelial precursor cells (EPC provide a continual source of replenishment for damaged or senescent blood vessels. In this review we discuss the biological relevance of circulating EPC in a variety of pathologies in order to build the case that these cells act as an endogenous mechanism of regeneration. Factors controlling EPC mobilization, migration, and function, as well as therapeutic interventions based on mobilization of EPC will be reviewed. We conclude by discussing several clinically-relevant approaches to EPC mobilization and provide preliminary data on a food supplement, Stem-Kine, which enhanced EPC mobilization in human subjects.

  13. Bone marrow–derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice

    Science.gov (United States)

    Koh, Young Jun; Kang, Shinae; Lee, Hyuek Jong; Choi, Tae-Saeng; Lee, Ho Sub; Cho, Chung-Hyun; Koh, Gou Young

    2007-01-01

    Little is known about whether bone marrow–derived circulating progenitor cells (BMDCPCs) can transdifferentiate into adipocytes in adipose tissues or play a role in expanding adipocyte number during adipose tissue growth. Using a mouse bone marrow transplantation model, we addressed whether BMDCPCs can transdifferentiate into adipocytes under standard conditions as well as in the settings of diet-induced obesity, rosiglitazone treatment, and exposure to G-CSF. We also addressed the possibility of transdifferentiation to adipocytes in a murine parabiosis model. In each of these settings, our findings indicated that BMDCPCs did not transdifferentiate into either unilocular or multilocular adipocytes in adipose tissues. Most BMDCPCs became resident and phagocytic macrophages in adipose tissues — which resembled transdifferentiated multilocular adipocytes by appearance, but displayed cell surface markers characteristic for macrophages — in the absence of adipocyte marker expression. When exposed to adipogenic medium in vitro, bone marrow cells differentiated into multilocular, but not unilocular, adipocytes, but transdifferentiation was not observed in vivo, even in the contexts of adipose tissue regrowth or dermal wound healing. Our results suggest that BMDCPCs do not transdifferentiate into adipocytes in vivo and play little, if any, role in expanding the number of adipocytes during the growth of adipose tissues. PMID:18060029

  14. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  15. Endothelial progenitor cells in cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    Poay; Sian; Sabrina; Lee; Kian; Keong; Poh

    2014-01-01

    Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.

  16. Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production

    Directory of Open Access Journals (Sweden)

    Khazaei Majid

    2011-02-01

    Full Text Available Abstract Background Epidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Obesity increases the expression of leptin, a multifunctional peptide produced predominantly by adipocytes which may promote tumor growth. Several recently experiments have suggested that the tumors growth is in need of endothelial progenitor cell (EPC dependent generation of new blood vessels. Our objectives in the present study were to examine the effects of leptin on melanoma growth, circulating EPCs number and plasma levels of nitric oxide metabolites (NOx. Methods 2 × 106 B16F10 melanoma cells were injected to thirty two C57BL6 mice subcutaneously. The mice were randomly divided into 4 groups (n = 8 in 8th day. Two groups were received twice daily intraperitoneal(i.p injections of either PBS or recombinant murine leptin (1 μg/g initial body weight. Two groups were received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week the animals were euthanized and blood samples and tumors were analyzed. Results The tumor weight, EPC numbers and NOx level in leptin, PBS, 9F8, and IgG group were (3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2,1.7 ± 0.3 g, (222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26/ml of blood, and (22.47 ± 5.5, 12.30 ± 1.5, 6.26 ± 0.84, 15.75 ± 6.3 μmol/L respectively. Tumors weight and size, circulating EPC numbers and plasma levels of NOx were significantly more in the leptin than 9f8 and both control groups (p Conclusions In conclusion, our observations indicate that leptin causes melanoma growth likely through increased NO production and circulating EPC numbers and consequently vasculogenesis.

  17. Circulating renalase, catecholamines, and vascular adhesion protein 1 in hypertensive patients.

    Science.gov (United States)

    Maciorkowska, Dominika; Zbroch, Edyta; Malyszko, Jolanta

    2015-11-01

    The aim of the study was to estimate and correlate circulating levels of renalase, vascular adhesion protein-1 (VAP-1), catecholamines in patients with primary hypertension. The renalase, VAP-1, and catecholamines concentration was estimated in 121 hypertensive patients. The correlation between renalase, VAP-1 levels and catecholamine concentration in blood, blood pressure control, pharmacological therapy, and medical history were taken in to consideration. The median office blood pressure was 145.5/86 mm Hg and was significantly higher than the median home blood pressure measurement value, which was 135/80 mm Hg, P hypertension comparing to healthy individuals (3.83 μg/mL and 248.37 ng/mL, P blood was observed (r = 0.549; P Hypertensive patients with diabetes mellitus had almost statistically significant higher VAP-1 concentration compared with hypertensive patients without diabetes mellitus (Me = 403.22 ng/mL vs. Me = 326,68 ng/mL, P = .064). In multiple regression analysis, renalase was predicted by plasma dopamine and norepinephrine as also diastolic office blood pressure and left ventricle ejection fraction. Circulating renalase and VAP-1 levels are elevated in patients with poor blood pressure control. Its correlation with noradrenalin concentration need further studies to find out the role of renalase as also VAP-1 in pathogenesis and treatment of hypertension. PMID:26403854

  18. Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

    Science.gov (United States)

    Farace, F; Gross-Goupil, M; Tournay, E; Taylor, M; Vimond, N; Jacques, N; Billiot, F; Mauguen, A; Hill, C; Escudier, B

    2011-01-01

    Background: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45−CD31+CD146+7-amino-actinomycin (7AAD)− cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45dimCD34+VEGFR2+7AAD− progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45dimCD34+VEGFR2+7AAD− progenitor cells, plasma factors, as well as day 1–day 14 changes in CEC, CD45dimCD34+VEGFR2+7AAD− progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined. Results: No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45dimCD34+VEGFR2+7AAD− progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007). Conclusion: Monitoring CD45dimCD34+VEGFR2+ progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome. PMID:21386843

  19. Circulating vascular endothelial growth factor is unaffected by acute hyperglycemia and hyperinsulinemia in type 1 diabetes mellitus

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Oomen, Peter H. N.; Sluiter, Wim J.

    2007-01-01

    Background: Circulating levels of vascular endothelial growth factor (VEGF) may predict microvascular complications in type 1 diabetes mellitus and are elevated when metabolic control is poor. We tested whether serum VEGF is influenced by prevailing glucose and insulin levels. Methods: In 15 type 1

  20. Mobilization of stem and progenitor cells in cardiovascular diseases

    OpenAIRE

    Wojakowski, W; Landmesser, U.; Bachowski, R; Jadczyk, T; M. Tendera

    2012-01-01

    Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the p...

  1. Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation.

    Directory of Open Access Journals (Sweden)

    Iván eRodríguez

    2014-09-01

    Full Text Available Physiological vascular function regulation is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the main risk factors of cardiovascular pathology, where the imbalance between the synthesis of vasodilator and vasoconstrictor molecules is common in the development of vascular disorders in systemic and placental circulation. In the placenta, an organ without autonomic innervations, the local control of vascular tone is critical for maintenance of fetal growth and mechanisms that underlie shear stress response induced by blood flow are essential during pregnancy. In this field, shear stress induced by moderate exercise is one of the most important mechanisms to improve vascular function through nitric oxide (NO synthesis and stimulation of mechanical response of endothelial cells triggered by ion channels, caveolae, endothelial NO synthase (eNOS and vascular endothelial growth factor (VEGF, among others. The demand for oxygen and nutrients by tissues and organs, especially in placentation and pregnancy, determines blood flow parameters and physiological adaptations of vascular beds for covering metabolic requirements. In this regard, moderate exercise versus sedentarism shows potential benefits for improving vascular function associated with the enhancement of molecular mechanisms induced by shear stress. In this review, we collect evidence about molecular bases of physiological response to shear stress in order to highlight the relevance of moderate exercise-training for vascular health in adult and fetal life.

  2. Improved homing of endothelial progenitor cells by the bispecific protein GPVI-CD133

    OpenAIRE

    Schönberger, T.; H. Langer; Gauß, A; Hafner, R; von der Ruhr, J; Schumm, M.; Bühring, HJ; van Zandvoort, M; Jung, G; Skutella, T.; Gawaz, M

    2011-01-01

    We designed a bifunctional protein, capable of capturing circulating endothelial progenitor cells to collagen-rich vascular lesions. The protein consists of the soluble platelet collagen receptor glycoprotein VI and an antibody to CD133. This construct substantially mediates EPC homing to vascular lesions. Furthermore, it augments reendothelialization of vascular lesions and reduces the extent of myocardial infarction. Therefore, this bifunctional protein could be a potential new therapeutic ...

  3. Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker.

    Directory of Open Access Journals (Sweden)

    Tatjana M H Niers

    Full Text Available BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (cVEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. METHODOLOGY: We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC and 12 patients with renal cell carcinoma (RCC. In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6, non-RCC: 6.2 IU/10(6 platelets, p = 0.001. In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001, and not related to platelet VEGF concentration. CONCLUSIONS: Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in

  4. Assessment of Cord Blood Vascular Endothelial Growth Factor Levels and Circulating CD34+ Cells in Preterm Infants with Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Azza Tawfeek Moawed, Nihad Ahmed El Nashar

    2012-04-01

    Full Text Available Respiratory distress syndrome (RDS secondary to surfactant deficiency is a common cause of mobility and mortality in premature infants. Vascular endothelial growth factor (VEGF is a major angiogenic factor and prime regulator of endothelial cells proliferation. So, VEGF may contribute to surfactant secretion and pulmonary maturation. Additionally, circulating CD34+ stem – progenitor cells are elevated along with its mobilizing cytokines in neonatal RDS. Aim of work: This study aimed to elucidate the role of cord blood VEGF and the circulating CD34+ cells in preterm infants with and without RDS. Patients & method: This study was conducted on 55 preterm neonates divided into 25 preterm (15 males/ 10 females without RDS with mean age of 31.60 ± 1.56 weeks and 30 preterm neonates with RDS (18 males/ 12 females with mean age of 29.95 ± 1.09 weeks . Twenty healthy neonates (14 males/ 6 females served as controls with mean age of 38.20 ± 3.57 weeks. All neonates were subjected to full history taking; thorough clinical examination and laboratory investigations including determination of VEGF levels in cord blood samples using ELISA and circulating CD34+ cells in peripheral blood by flowcytometery. Results:The results of this study revealed that cord blood VEGF levels were significantly decreased in preterms with RDS versus preterms without RDS and controls with p values of both < 0.0001. Furthermore, the circulating CD34+ cells were significantly increased in preterm infants with RDS versus preterm infants without RDS and controls (p < 0.05 & < 0.0001 respectively. Premature rupture of the membrane, gender of the newborn, birth weight and antenatal steroid administration had neither significant effect on the cord blood VEGF nor on the number of CD34+ cells. There was inverse significant correlation between GA and the number of CD34+ cells. Conclusion:It was concluded that low cord blood VEGF is associated with RDS and its level negatively

  5. Association Between Circulating Early Endothelial Progenitors and CD4+CD25+ Regulatory T Cells: A Possible Cross-talk between Immunity and Angiogenesis?

    Directory of Open Access Journals (Sweden)

    Shmuel Schwartzenberg

    2005-01-01

    Full Text Available Regulatory T-cells (Treg are a recently defined subset of CD4+ cells that can suppress inflammation and induce tolerance. Phenotypically, T-regs are characterized by a high level of expression of the IL-2 receptor alpha chain, CD25. Endothelial progenitor cells (EPCs can transform into mature endothelial cells and promote vessel formation by inducing postnatal angiogenesis and vasculogenesis. Herein, we tested the hypothesis that an association exists between circulating EPC and Tregs that could potentially allude to cross talk between immunity and angiogenesis. Peripheral blood mononuclear cells were isolated by Ficoll density-gradient centrifugation from 28 subjects. Circulating number of EPCs at various developmental stages (CD133+CD34+, CD133+VEGFR2+, CD34+VEGFR2+, total CD4+ and Treg CD4+CD25high numbers were determined by FACS analysis. We found a positive correlation between early progenitor cell (CD133+CD34+ number and Tregs, but no correlation between differentiated EPCs and Tregs, or between CD4+ and any of the EPCs sampled. Early EPCs (CD133+CD34+ did not correlate with CD34+/KDR or with CD133/KDR cells. Circulating numbers of early but not ‘mature’ EPC correlate with Tregs but not CD4 numbers. This finding may suggest a novel role for Tregs in promoting EPC recruitment or delaying EPC maturation.

  6. Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

    OpenAIRE

    Farace, F.; Gross-Goupil, M; Tournay, E; Taylor, M; Vimond, N.; Jacques, N; Billiot, F.; Mauguen, A.; Hill, C.; Escudier, B

    2011-01-01

    Background: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) a...

  7. Endothelial progenitor cells in mothers of low-birthweight infants: a link between defective placental vascularization and increased cardiovascular risk?

    LENUS (Irish Health Repository)

    King, Thomas F J

    2013-01-01

    Offspring birthweight is inversely associated with future maternal cardiovascular mortality, a relationship that has yet to be fully elucidated. Endothelial progenitor cells (EPCs) are thought to play a key role in vasculogenesis, and EPC numbers reflect cardiovascular risk.

  8. Growth factor-and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization

    Institute of Scientific and Technical Information of China (English)

    Philip V.Peplow

    2014-01-01

    Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes speciifc growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli-al progenitor cells migrate and home to speciifc sites following ischemic stroke via growth factor/cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch-emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovas-cularization following ischemic stroke.

  9. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progeni

  10. Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome.

    Science.gov (United States)

    Berezin, Alexander E; Kremzer, Alexander A; Berezina, Tatyana A; Martovitskaya, Yulia V; Gronenko, Elena A

    2016-09-01

    Metabolic syndrome (MetS) is defined as cluster of multiple metabolic and cardiovascular (CV) abnormalities included abdominal obesity, high-normal blood pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has a growing prevalence worldwide. We investigated whether an elevated level of osteoprotegerin (OPG) predicts imbalance between different phenotypes of circulating endothelial (EPCs) and mononuclear (MPCs) progenitor cells in MetS patients. We have analyzed data regarding dysmetabolic disorder subjects without known CV disease), as well as with known type two diabetes mellitus. All patients have given their informed written consent for participation in the study. This article contains data on the independent predictors of depletion in numerous of circulating EPCs and MPCs in MetS patients. The data are supplemental to our original research article describing detailed associations of elevated OPG level in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk factors. PMID:27508223

  11. Pulmonary Vascular Stiffness: Measurement, Modeling, and Implications in Normal and Hypertensive Pulmonary Circulations

    OpenAIRE

    Hunter, Kendall S.; Lammers, Steven R.; Shandas, Robin

    2011-01-01

    This article introduces the concept of pulmonary vascular stiffness, discusses its increasingly recognized importance as a diagnostic marker in the evaluation of pulmonary vascular disease, and describes methods to measure and model it clinically, experimentally, and computationally. It begins with a description of systems-level methods to evaluate pulmonary vascular compliance and recent clinical efforts in applying such techniques to better predict patient outcomes in pulmonary arterial hyp...

  12. Prognostic significance of preoperative circulating vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma:A prospective study

    Institute of Scientific and Technical Information of China (English)

    Kuo-Shyang Jeng; I-Shyan Sheen; Yi-Ching Wang; Shu-Ling Gu; Chien-Ming Chu; Shou-Chuan Shih; Po-Chuan Wang; Wen-Hsing Chang; Horng-Yuan Wang

    2004-01-01

    AIM: To investigate the prognostic value of vascular endothelial growth factor messenger RNA (VEGF mRNA) in the peripheral blood (PB) of patients with hepatocellular carcinoma (HCC) undergoing curative resection.METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA in the PB was determined prospectively in 50 controls and in 50 consecutive patients undergoing curative resection for HCC.RESULTS: Among the isoforms of VEGF mRNA, VEGF165 and VEGF121 were expressed. By multivariate analysis, a higher level of VEGF165 in preoperative PB correlated with a risk of HCC recurrence with borderline significance (P=0.050) and significantly with recurrence-related mortality (P=0.048);while VEGF121 did not. Other significant predictors of HCC recurrence included cellular dedifferentiation (P=0.033),an absent or incomplete capsule (P=0.020), vascular permeation (P=0.018), and daughter nodules (P=0.006).The other significant parameter of recurrence related mortality was cellular dedifferentiation (P=0.053). The level of circulating VEGF mRNA, however, did not significantly correlate with tumor size, cellular differentiation, capsule,daughter nodules, vascular permeation, necrosis and hemorrhage of tumors.CONCLUSION: The preoperative level of circulating VEGF mRNA, especially isoform VEGF165, plays a significant role in the prediction of postoperative recurrence of HCC.

  13. Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    contained considerable amounts of VEGF. In isolated lymphocytes and monocytes, VEGF was not present in measurable amounts. The number of neutrophils was significantly (p<0.0001) correlated to VEGF concentrations in lysed whole blood, but not to VEGF concentrations in plasma or serum. The number of platelets...... clotting. CONCLUSION: Circulating neutrophils contain considerable amounts of VEGF that contribute to high VEGF levels in lysed whole blood. VEGF in circulating platelets contributes to high VEGF levels in serum and lysed whole blood. Allowing whole blood samples to clot for between 2 and 6 h before serum......AIM: The sources of increased vascular endothelial growth factor (VEGF) concentrations in peripheral blood from cancer patients are not known in detail. The aim of the present study was to evaluate correlations between the VEGF content in isolated leucocyte subpopulations and VEGF concentrations in...

  14. Endothelial Progenitor Cells Promote Directional Three-Dimensional Endothelial Network Formation by Secreting Vascular Endothelial Growth Factor

    OpenAIRE

    Yoshinori Abe; Yoshiyuki Ozaki; Junichi Kasuya; Kimiko Yamamoto; Joji Ando; Ryo Sudo; Mariko Ikeda; Kazuo Tanishita

    2013-01-01

    Endothelial progenitor cell (EPC) transplantation induces the formation of new blood-vessel networks to supply nutrients and oxygen, and is feasible for the treatment of ischemia and cardiovascular diseases. However, the role of EPCs as a source of proangiogenic cytokines and consequent generators of an extracellular growth factor microenvironment in three-dimensional (3D) microvessel formation is not fully understood. We focused on the contribution of EPCs as a source of proangiogenic cytoki...

  15. Circulating hematopoietic progenitors and CD34+ cells predicted successful hematopoietic stem cell harvest in myeloma and lymphoma patients: experiences from a single institution

    Directory of Open Access Journals (Sweden)

    Yu JT

    2016-02-01

    Full Text Available Jui-Ting Yu,1,2,* Shao-Bin Cheng,3,* Youngsen Yang,1 Kuang-Hsi Chang,4 Wen-Li Hwang,1 Chieh-Lin Jerry Teng,1,5,6 1Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, 2Division of Hematology/Medical Oncology, Tungs' Taichung MetroHarbor Hospital, 3Division of General Surgery, Department of Surgery, 4Department of Medical Research and Education, Taichung Veterans General Hospital, 5Department of Life Science, Tunghai University, 6School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China *These authors contributed equally to this work Background: Previous studies have shown that the numbers of both circulating hematopoietic progenitor cell (HPC and CD34+ cell are positively correlated with CD34+ cell harvest yield. However, the minimal numbers of both circulating HPCs and CD34+ cells required for performing an efficient hematopoietic stem cell (HSC harvest in lymphoma and myeloma patients have not been defined in our institution. Patients and methods: Medical records of 50 lymphoma and myeloma patients undergoing peripheral blood HSC harvest in our institution were retrospectively reviewed. The minimal and optimal HSC harvest yield required for the treatment was considered to be ≥2×106 CD34+ cells/kg and ≥5×106 CD34+ cells/kg, respectively. Results: The minimally required or optimal HSC yield obtained was not influenced by age (≥60 years, sex, underlying malignancies, disease status, multiple rounds of chemotherapy, or history of radiotherapy. The numbers of both circulating HPC and CD34+ cell were higher in patients with minimally required HSC yields (P=0.000 for HPC and P=0.000 for CD34+ cell and also in patients with optimal HSC yields (P=0.011 for HPC and P=0.006 for CD34+ cell. The cell count cutoff for obtaining minimally required HSC harvest was determined to be 20/mm3 for HPCs and 10/mm3 for CD34+ cells. Furthermore, the cell count cutoff for obtaining

  16. [Physical and physiological principles of calculating vascular resistance in cardiovascular circulation].

    Science.gov (United States)

    Hennig, E

    1992-01-01

    After reconstructive vascular surgery the quality of perfusion and the risk of failure can be predicted, if the distal outflow resistance of the graft is known. The laws of the hydrodynamics for the calculation of flow resistance in tubes are discussed with respect to their validity in the circulatory system. Because of great differences between the physiological realities and the physical assumption, and problems in monitoring some of the parameters of the equations, the calculation of the physiological vascular resistance according to the a.m. laws is not possible. With "Ohms law" of the hydrodynamic the calculation of the outflow resistance distal of a graft is possible if the flow through the bypass and the pressure losses in the outflow bed are known. Easier to perform is the measurement of the pressure-time integral generated by the injection of a standardized volume into the graft and the calculation of the outflow resistance with the help of a microprocessor. PMID:1529426

  17. Usefulness of circulating vascular endothelial growth factor and neutrophil elastase as diagnostic markers of disseminated intravascular coagulation in non-cancer patients

    OpenAIRE

    Joo, Shin Young; Kim, Ji-Eun; Kim, Ju Young; Han, Kyou-Sup; Kim, Hyun Kyung

    2010-01-01

    Background Disseminated intravascular coagulation (DIC) is characterized by platelet and neutrophil activation. Platelets are the major source of circulating vascular endothelial growth factor (VEGF). Endostatin, an anti-angiogenic factor, is a fragment of collagen that is released from the extracellular matrix via the active cleavage of neutrophil elastase, thereby increasing the circulating level of endostatin. Hypercoagulable conditions such as DIC may induce the release of VEGF and neutro...

  18. The role of lipid dysregulation and vascular risk factors in glaucomatous retrobulbar circulation

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    Monika Modrzejewska

    2015-03-01

    Full Text Available The aim of this study was to evaluate selected lipid-related and vascular factors and their effect on retrobulbar hemodynamics in glaucoma. Fifty-six patients with primary open angle glaucoma (POAG [POAG group; mean age 68.32 years (SD±0.21] and 54 patients in control group [CG, mean age 68.1 years (SD±5.34] were examined. Peak systolic velocity, end-diastolic velocity, mean velocity, pulsatility index, and resistive index of the ophthalmic artery, the central retinal artery and the posterior ciliary arteries were measured by Color Doppler Imaging. Selected lipid-related, systemic and local vascular parameters were evaluated. Statistical methods included Shapiro-Wilk, Student-t and Mann-Whitney U tests, and Spearman rank correlations. In POAG group systolic arterial blood pressure, diastolic arterial blood pressure, total cholesterol, low density lipoprotein cholesterol (LDL-ch, and intraocular pressure were significantly higher; while ocular perfusion pressure, high density lipoprotein cholesterol (HDL-ch and diastolic ocular perfusion pressure were significantly lower (p≤0.05. Color Doppler Imaging confirmed blood flow abnormalities in all investigated arteries. In addition, significant correlations of HDL-ch, LDL-ch and triglycerides (TG with peak systolic velocity, end-diastolic velocity and mean velocity were found in individual arteries (p≤0.05. Also, significant associations of systolic arterial blood pressure, ocular perfusion pressure, systolic oclular perfusion pressure and diastolic ocular perfusion pressure with peak systolic velocity, end-diastolic velocity, mean velocity and resistive index were revealed in the posterior ciliary arteries (p≤0.05. Dysregulation of lipid-related and vascular factors, as well as statistical correlation between the above and retrobulbar blood flow indices, might imply their role in vasoconstrictive processes during glaucomatous endotheliopathy.

  19. The resistance-compliance product of the pulmonary circulation varies in health and pulmonary vascular disease.

    Science.gov (United States)

    Hadinnapola, Charaka; Li, Qiuju; Su, Li; Pepke-Zaba, Joanna; Toshner, Mark

    2015-04-01

    Pulmonary vascular resistance (PVR) is traditionally used to describe pulmonary hemodynamic characteristics. However, it does not take into account pulmonary artery compliance (Ca) or pulsatile flow. The product of PVR and Ca is known as RC time. Previous studies assert that the PVR-Ca relationship is fixed and RC time is constant between health and disease states. We hypothesized that RC time was not constant in health and pulmonary vascular disease. Right heart catheterizations performed in Papworth Hospital over a 6 year period were analyzed. Subjects were divided into those with normal pulmonary hemodynamics (NPH group; n = 156) and pulmonary arterial hypertension (PAH group; n = 717). RC time and the right ventricle (RV) oscillatory power fraction were calculated. RC time for the NPH group (0.47 ± 0.13 sec) is significantly lower than the PAH group (0.56 ± 0.16 sec; P < 0.0001). The RV oscillatory power fraction is lower in the NPH group (P < 0.0001). RC time correlates inversely with the RV oscillatory power fraction in each group. We conclude, there is an inverse relationship between PVR and Ca, however, this relationship is not always fixed. Consequently, RC time is significantly lower in health compared to disease with elevated pulmonary artery pressures. PAH leads to a decrease in cardiac efficiency. PMID:25902784

  20. Circulating CD133+CD34+ progenitor cells inversely correlate with soluble ICAM-1 in early ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Frank Joseph

    2011-08-01

    Full Text Available Abstract Background and Purpose Both endothelial progenitor cells (EPC and markers of neuroinflammation are candidate biomarkers for stroke severity and outcome prediction. A relationship between EPC and neuroinflammatory markers in early stroke is not fully elucidated. The objectives were to investigate correlations between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E-selectin, tumor necrosis factor (TNF-α, interleukin (IL-6, endothelin (ET-1, markers of tissue injury (matrix metalloproteinases (MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP-1 in early stroke patients. Methods We prospectively recruited symptomatic patients with ischemic cerebrovascular disease. We assessed stroke severity by using of acute (diffusion-weighted imaging (DWI and final lesion volumes (fluid attenuated inversion recovery (FLAIR. We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9, TIMP-1 and plasma TNF-α, IL-6, ET-1 by ELISA, and quantified EPC in mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD age 62(14, with admission National Institutes of Health Stroke Scale (NIHSS 10(8 selected from 175 patients with imaging confirmed ischemic stroke. Non-parametric statistics, univariate and multivariate analysis were used. Results Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r = -0.6, p Conclusion Our study showed that high ICAM-1 is associated with low CD133+CD34+subset of EPC. Biomarkers of neuroinflammation may predict tissue injury and stroke severity in early ischemia.

  1. Circulating level of microRNA-126 may be a potential biomarker for recovery from smoking-related vascular damage in middle-aged habitual smokers

    Directory of Open Access Journals (Sweden)

    Tomonori Sugiura

    2015-06-01

    Conclusions: Endothelial damage was improved and plasma levels of circulating miR-126 were increased after 8 weeks of smoking cessation. These findings suggested a potential use of miR-126 as a biomarker for recovery from smoking-induced vascular damage.

  2. Surface expression of CXCR4 on circulating CD133+ progenitor cells is associated with plaque instability in subjects with carotid artery stenosis

    Directory of Open Access Journals (Sweden)

    Sadikovic Suwad

    2009-12-01

    Full Text Available Abstract Background Circulating progenitor cells (PCs are considered to contribute to the remodeling of atherosclerotic plaques. Their surface receptor CXCR4 plays an important role in the recruitment of PCs to their target. This study compares the mobilization of PCs and their functional characteristics in asymptomatic subjects with stable and with unstable carotid plaques. This could provide insight into plaque remodeling and help to develop biomarkers for plaque stability. Methods In 31 subjects with asymptomatic carotid artery stenosis we analyzed the number of CD133+ PCs, VEGFR2+CD34+ PCs and the surface expression of CXCR4 on CD133+ PCs by flow cytometry. Subjects underwent bilateral carotid MRI in a 1.5-T scanner in order to allow the categorization of plaques, following the modified criteria of the American Heart Association. Results The number of CD133+ PCs and VEGFR2+CD34+ PCs showed no significant difference between subjects with stable and unstable carotid plaques. The expression of CXCR4 on CD133+ PCs was higher in subjects with unstable plaques than in subjects with stable plaques (p = 0.009. Conclusions This study demonstrates an association between functional characteristics of circulating CD133+ PCs and plaque stability in subjects with asymptomatic carotid artery stenosis. The higher expression of CXCR4 on CD133+ PCs suggests a difference in the recruitment of PCs to the injured tissue in subjects with unstable plaques and subjects with stable plaques. As surface expression of CXCR4 on CD133+ PCs differs in subjects with unstable and with stable plaques, CXCR4 is a promising candidate for a serological biomarker for plaque stability.

  3. A modular mock circulation for hydromechanical studies on valves, stenoses, vascular grafts and cardiac assist devices.

    Science.gov (United States)

    Schima, H; Baumgartner, H; Spitaler, F; Kuhn, P; Wolner, E

    1992-07-01

    P6vices for hydrodynamic simulation are required in a variety of studies such as device evaluation, cardiovascular modeling and for student training. Most studies today use different, incompatible circuits, which must be redesigned for every new application. To obtain a universal apparatus, a unitized system with standard connectors was developed. Three types of connectors were selected: 1" flange connectors, 1/2" tubing connectors and Luer-connectors with a 2 mm lumen. The complete system consists of reservoirs, throttles, valve holders, adapters for Doppler ultrasound probes, and converters to link these basic diameters. The apparatus can be driven by membrane, centrifugal and geared pumps. The system has successfully been used in echocardiographic studies of stenosis and valvular insufficiency, for pulse propagation in vascular grafts, and to test the hydraulic performance of cardiac assist devices. Flow rates between 0.1 and 30 l/min and pressure gradients up to 250 mmHg were achieved. In practical use, the system can be adapted to suit various investigations, with minimal expense. Standardization of the parts and connectors results in simple documentation and good reproducibility. PMID:1516993

  4. Vascular Stem/Progenitor Cell Migration Induced by Smooth Muscle Cell-Derived Chemokine (C-C Motif) Ligand 2 and Chemokine (C-X-C motif) Ligand 1 Contributes to Neointima Formation.

    Science.gov (United States)

    Yu, Baoqi; Wong, Mei Mei; Potter, Claire M F; Simpson, Russell M L; Karamariti, Eirini; Zhang, Zhongyi; Zeng, Lingfang; Warren, Derek; Hu, Yanhua; Wang, Wen; Xu, Qingbo

    2016-09-01

    Recent studies have shown that Sca-1(+) (stem cell antigen-1) stem/progenitor cells within blood vessel walls may contribute to neointima formation, but the mechanism behind their recruitment has not been explored. In this work Sca-1(+) progenitor cells were cultivated from mouse vein graft tissue and found to exhibit increased migration when cocultured with smooth muscle cells (SMCs) or when treated with SMC-derived conditioned medium. This migration was associated with elevated levels of chemokines, CCL2 (chemokine (C-C motif) ligand 2) and CXCL1 (chemokine (C-X-C motif) ligand 1), and their corresponding receptors on Sca-1(+) progenitors, CCR2 (chemokine (C-C motif) receptor 2) and CXCR2 (chemokine (C-X-C motif) receptor 2), which were also upregulated following SMC conditioned medium treatment. Knockdown of either receptor in Sca-1(+) progenitors significantly inhibited cell migration. The GTPases Cdc42 and Rac1 were activated by both CCL2 and CXCL1 stimulation and p38 phosphorylation was increased. However, only Rac1 inhibition significantly reduced migration and p38 phosphorylation. After Sca-1(+) progenitors labeled with green fluorescent protein (GFP) were applied to the adventitial side of wire-injured mouse femoral arteries, a large proportion of GFP-Sca-1(+) -cells were observed in neointimal lesions, and a marked increase in neointimal lesion formation was seen 1 week post-operation. Interestingly, Sca-1(+) progenitor migration from the adventitia to the neointima was abrogated and neointima formation diminished in a wire injury model using CCL2(-/-) mice. These findings suggest vascular stem/progenitor cell migration from the adventitia to the neointima can be induced by SMC release of chemokines which act via CCR2/Rac1/p38 and CXCR2/Rac1/p38 signaling pathways. Stem Cells 2016;34:2368-2380.

  5. Dual role of circulating endothelial progenitor cells in stent struts endothelialisation and neointimal regrowth: A substudy of the IN-PACT CORO trial

    Energy Technology Data Exchange (ETDEWEB)

    De Maria, Giovanni Luigi [Institute of Cardiology, Catholic University of the Sacred Heart, Rome (Italy); Porto, Italo, E-mail: italo.porto@gmail.com [Institute of Cardiology, Catholic University of the Sacred Heart, Rome (Italy); Interventional Cardiology Unit, San Donato Hospital, Arezzo (Italy); Burzotta, Francesco; Brancati, Marta Francesca; Trani, Carlo; Pirozzolo, Giancarlo; Leone, Antonio Maria; Niccoli, Giampaolo [Institute of Cardiology, Catholic University of the Sacred Heart, Rome (Italy); Prati, Francesco [Department of Interventional Cardiology, San Giovanni Hospital, Rome (Italy); Crea, Filippo [Institute of Cardiology, Catholic University of the Sacred Heart, Rome (Italy)

    2015-01-15

    Background: Endothelialisation is a crucial event after percutaneous coronary intervention (PCI). Endothelial progenitor cells (EPCs) are bone marrow derived elements with reparative properties. We aimed to assess the relationship between circulating EPC levels and stent neointimal hyperplasia (NIH) using frequency domain optical coherence tomography (FD-OCT). Methods: Patients undergoing elective PCI to native vessels and randomised to bare metal stent (BMS) alone versus BMS plus drug coated balloon (DCB) were included. At six months, angiographic follow-up and FD-OCT were performed to measure percentage neointimal hyperplasia volume obstruction (%NIHV), and percentage of uncovered stent struts (%US). Venous blood samples were obtained before the procedure and at six months to detect CD34+CD45dimKDR + EPC levels. Results: Twenty patients were enrolled. A significant relationship was observed between baseline EPC levels and %NIHV (R: 0.63, p: 0.03) and %US (R: − 0.56, p: 0.01) at follow-up. Both EPC levels and DCB use were independently related to %NIHV (β: 0.55; p < 0.001 and β: − 0.51; p: 0.001, respectively), while only EPC levels were independently associated to %US (β: − 0.52; p: 0.01). Higher %NIHV (p: 0.004) and lower %US (p: 0.005) were observed in patients with stable or increasing EPC level. Conclusion: Our study shows a relationship between EPC levels and stent strut coverage, supporting a dual role for these cells in favouring stent endothelialisation but also NIH growth. - Highlights: • Substudy of IN-PACT CORO trial comparing, by adoption of optical coherence tomography, the amount of neointimal growth and stent struts coverage at six months of follow up, in elective patients randomised to conventional PCI with bare metal stent implantation (BMS group) or to stent implantation with pre or postdilation with a drug coated balloon (BMS + DCB group) • Lower neointimal regrowth observed in BMS + DCB group • First in vivo demonstration that

  6. Dual role of circulating endothelial progenitor cells in stent struts endothelialisation and neointimal regrowth: A substudy of the IN-PACT CORO trial

    International Nuclear Information System (INIS)

    Background: Endothelialisation is a crucial event after percutaneous coronary intervention (PCI). Endothelial progenitor cells (EPCs) are bone marrow derived elements with reparative properties. We aimed to assess the relationship between circulating EPC levels and stent neointimal hyperplasia (NIH) using frequency domain optical coherence tomography (FD-OCT). Methods: Patients undergoing elective PCI to native vessels and randomised to bare metal stent (BMS) alone versus BMS plus drug coated balloon (DCB) were included. At six months, angiographic follow-up and FD-OCT were performed to measure percentage neointimal hyperplasia volume obstruction (%NIHV), and percentage of uncovered stent struts (%US). Venous blood samples were obtained before the procedure and at six months to detect CD34+CD45dimKDR + EPC levels. Results: Twenty patients were enrolled. A significant relationship was observed between baseline EPC levels and %NIHV (R: 0.63, p: 0.03) and %US (R: − 0.56, p: 0.01) at follow-up. Both EPC levels and DCB use were independently related to %NIHV (β: 0.55; p < 0.001 and β: − 0.51; p: 0.001, respectively), while only EPC levels were independently associated to %US (β: − 0.52; p: 0.01). Higher %NIHV (p: 0.004) and lower %US (p: 0.005) were observed in patients with stable or increasing EPC level. Conclusion: Our study shows a relationship between EPC levels and stent strut coverage, supporting a dual role for these cells in favouring stent endothelialisation but also NIH growth. - Highlights: • Substudy of IN-PACT CORO trial comparing, by adoption of optical coherence tomography, the amount of neointimal growth and stent struts coverage at six months of follow up, in elective patients randomised to conventional PCI with bare metal stent implantation (BMS group) or to stent implantation with pre or postdilation with a drug coated balloon (BMS + DCB group) • Lower neointimal regrowth observed in BMS + DCB group • First in vivo demonstration that

  7. FLAIR vascular hyperintensities and dynamic 4D angiograms for the estimation of collateral blood flow in posterior circulation occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Foerster, Alex; Wenz, Holger; Kerl, Hans Ulrich; Al-Zghloul, Mansour; Habich, Sonia; Groden, Christoph [University of Heidelberg, Department of Neuroradiology, Universitaetsmedizin Mannheim, Mannheim (Germany)

    2014-09-15

    The objectives of this paper are to assess collateral blood flow in posterior circulation occlusion by MRI-based approaches (fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs), collateralization on dynamic 4D angiograms) and investigate its relation to ischemic lesion size and growth. In 28 patients with posterior cerebral artery (PCA) and 10 patients with basilar artery (BA) occlusion, MRI findings were analyzed, with emphasis on distal FVH and collateralization on dynamic 4D angiograms. In PCA occlusion, distal FVH was observed in 18/29 (62.1 %), in BA occlusion, in 8/10 (80 %) cases. Collateralization on dynamic 4D angiograms was graded 1 in 8 (27.6 %) patients, 2 in 1 (3.4 %) patient, 3 in 12 (41.4 %) patients, and 4 in 8 (27.6 %) patients with PCA occlusion and 0 in 1 (10 %) patient, 2 in 3 (30 %) patients, 3 in 1 (10 %) patient, and 4 in 5 (50 %) patients with BA occlusion. FVH grade showed neither correlation with initial or follow-up diffusion-weighted image (DWI) lesion size nor DWI-perfusion-weighted imaging (PWI) mismatch ratio. Collateralization on dynamic 4D angiograms correlated inversely with initial DWI lesion size and moderately with the DWI-(PWI) mismatch ratio. The combination of distal FVH and collateralization grade on dynamic 4D angiograms correlated inversely with initial as well as follow-up DWI lesion size and highly with the DWI-PWI mismatch ratio. In posterior circulation occlusion, FVH is a frequent finding, but its prognostic value is limited. Dynamic 4D angiograms are advantageous to examine and graduate collateral blood flow. The combination of both parameters results in an improved characterization of collateral blood flow and might have prognostic relevance. (orig.)

  8. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

    Full Text Available Age is a significant risk factor for the development of vascular diseases, such as atherosclerosis. Although pharmacological treatments, including statins and anti-hypertensive drugs, have improved the prognosis for patients with cardiovascular disease, it remains a leading cause of mortality in those aged 65 years and over. Furthermore, given the increased life expectancy of the population in developed countries, there is a clear need for alternative treatment strategies. Consequently, the relationship between aging and progenitor cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs play an integral role in the cellular repair mechanisms for endothelial regeneration and maintenance. However, EPCs are subject to age-associated changes that diminish their number in circulation and function, thereby enhancing vascular disease risk. A great deal of research is aimed at developing strategies to harness the regenerative capacity of these cells.In this review, we discuss the current understanding of the cells termed ‘EPCs’, examine the impact of age on EPC-mediated repair and identify therapeutic targets with potential for attenuating the age-related decline in vascular health via beneficial actions on EPCs.

  9. Effects of Replenishing Qi, Promoting Blood Circulation and Resolving Phlegm on Vascular Endothelial Function and Blood Coagulation System in Senile Patients with Hyperlipemia

    Institute of Scientific and Technical Information of China (English)

    Yang Huimin; Han Libei; Sheng Tong; He Qiong; Liang Jinpu

    2006-01-01

    Objective: To observe the curative effect of the method of replenishing qi, promoting blood circulation and resolving phlegm on senile hyperlipemia and its effects on vascular endothelial function and blood coagulation system. Method: 96 patients with senile hyperlipemia were randomly divided into a treatment group and a of blood lipid, vascular endothelial function, blood coagulation system and safety. Results: After treatment,the treatment group was obviously superior to the control group (P<0.05) in reducing plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as well as in the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-keto-PGF1α), D-dimer (D-D) and fibrinogen (FIB). Conclusion: Danshen Jueming Granules have the effect of regulating metabolism of blood lipid, and improving vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.

  10. Fluid flow along venous adventitia in rabbits: is it a potential drainage system complementary to vascular circulations?

    Directory of Open Access Journals (Sweden)

    Hong-yi Li

    Full Text Available BACKGROUND: Our previous research and other studies with radiotracers showed evidence of a centripetal drainage pathway, separate from blood or lymphatic vessels, that can be visualized when a small amount of low molecular weight tracer is injected subcutaneously into a given region on skin of humans. In order to further characterize this interesting biological phenomenon, animal experiments are designed to elucidate histological and physiologic characteristics of these visualized pathways. METHODS: Multiple tracers are injected subcutaneously into an acupuncture point of KI3 to visualize centripetal pathways by magnetic resonance imaging or fluorescein photography in 85 healthy rabbits. The pathways are compared with venography and indirect lymphangiography. Fluid flow through the pathways is observed by methods of altering their hydrated state, hydrolyzing by different collagenases, and histology is elucidated by optical, fluorescein and electron microscopy. RESULTS: Histological and magnetic imaging examinations of these visualized pathways show they consist of perivenous loose connective tissues. As evidenced by examinations of tracers' uptake, they appear to function as a draining pathway for free interstitial fluid. Fluorescein sodium from KI3 is found in the pathways of hind limbs and segments of the small intestines, partial pulmonary veins and results in pericardial effusion, suggesting systematical involvement of this perivenous pathway. The hydraulic conductivity of these pathways can be compromised by the collapse of their fiber-rich beds hydrolyzed by either of collagenase type I, III, IV or V. CONCLUSIONS: The identification of pathways comprising perivenous loose connective tissues with a high hydraulic conductivity draining interstitial fluid in hind limbs of a mammal suggests a potential drainage system complementary to vascular circulations. These findings may provide new insights into a systematically distributed collagenous

  11. Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells.

    Directory of Open Access Journals (Sweden)

    Dilyana Todorova

    Full Text Available BACKGROUND: Circulating CD34(+ cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN could target progenitor cell injury by Natural Killer (NK cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+-derived Endothelial Colony Forming Cells (ECFC can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+ progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+ cells expressing FKN was identified as an independent variable inversely correlated to CD34(+ progenitor cell count. We further showed that treatment of CD34(+ circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+ progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients.

  12. Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study

    OpenAIRE

    2015-01-01

    Introduction Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselected cohorts of SSc and MCTD. Methods Sera of SSc patients (N = 298) and MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included. Blood donors were included a...

  13. Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density and improve heart function in a rat cellular cardiomyoplasty model

    Institute of Scientific and Technical Information of China (English)

    SDAVANI; NMERSIN; BROYER; BKANTELIP; JPKANTELIP

    2004-01-01

    AIM: Cellular cardiomyoplasty is promising for improving postinfarcted cardiac function. Over the past decade, a variety of cell types have been proposed including mononuclear bone marrow cells. The latter contains different lineages including mesenchymal stem cells (MSCs). The aim of this study was to analyse the differentiation pathways of engrafted syngenic mesenchymal progenitor cells (MPCs) obtained in culture from bone marrow

  14. Correlation between Circulating Levels of Pro-Inflammatory Cytokines TNF-alpha and Vascular Calcification Inhibitor Matrix Gla Protein in Obese Men

    Directory of Open Access Journals (Sweden)

    Trilis Yulianti

    2010-12-01

    Full Text Available BACKGROUND: Adult obesity is rapidly increasing in the world including Indonesia. Tumor necrosis factor α (TNF-α was chronically elevated in obese adipose tissue. TNF-α, a pleiotropic cytokine and also a regulator of bone formation, may might represent an important link between obesity and vascular calcification. Elegant genetic studies in mice and human have highlighted the important roles for Matrix Gla Protein (MGP as an inhibitor of vascular calcification. The aim of this study was to examine the correlation between circulating levels of pro-inflammatory cytokines TNF-α and vascular calcification inhibitor MGP in obese men. METHODS: This was an observational cross-sectional study including 40 central obese men (waist circumference ≥90 cm aged 31-60 years old. Serum MGP and serum TNF-α concentrations were quantified by ELISA principle. Fasting plasma glucose was assessed using hexokinase methods, triglyceride by GPO-PAP methods, and creatinine by Jaffe methods. All assays were performed according to the manufacture instruction. Statistical analysis was performed with SPSS for windows ver 16. Univariate analysis were performed to analyze mean, maximum, minimum value and SD. Pearson correlation statistic were performed to determine the correlation between variables. Significance value were define as alpha level=0.05 based on two-tailed tests. RESULTS: The cross-sectional study (n=40 showed that the advancing age was correlated with plasma TNF-α concentration (r = 0.348; p = 0.028. The mean concentration of TNF-α and MGP were 8.323 and 8.368, respectively. We found a significant negative correlation between TNF-α with MGP (r=-0.425; p=0.006 and a significant correlation between TNF-α and triglyceride (r=0.375; p=0.017. CONCLUSIONS: Circulating level of TNF-α was inversely correlated with MGP concentration in obese men. This finding suggested that high level TNF-α leads to low MGP concentration obese men, hence, limits inhibitory

  15. Characteristics of vascular lesions in patients with posterior circulation infarction according to age and region of infarct

    Institute of Scientific and Technical Information of China (English)

    Daopei Zhang; Shuling Zhang; Hongtao Zhang; Yuming Xu

    2012-01-01

    Patients with posterior circulation infarction underwent CT angiography and magnetic resonance angiography. Intracranial and extracranial vasculopathy was evaluated according to age group and location of stroke. Patients aged > 60 years and 60 years than 60 years, whereas vertebrobasilar artery developmental anomalies occurred with similar frequency in patients aged 60 years. Patients with infarction of the brainstem or cerebellum were more likely to have vertebral artery stenosis or occlusion, basilar artery stenosis or occlusion, vertebral artery dominance or tortuosity, and basilar artery tortuosity, and patients with infarction of the thalamus, medial temporal, or occipital lobes were more likely to have stenosis or occlusion of the vertebral or basilar arteries. Vertebrobasilar artery tortuosity, vertebral artery dominance (hypoplasia), and congenital variations of the vertebrobasilar system may lead to posterior circulation infarction at different locations in different age groups.

  16. Acute response of circulating vascular regulating microRNAs during and after high-intensity and high-volume cycling in children

    Directory of Open Access Journals (Sweden)

    Yvonne eKilian

    2016-03-01

    Full Text Available Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126 and the VEGF mRNA following an acute bout of HIIT and HVT in children. Methods: Twelve healthy competitive young male cyclists (14.4 ± 0.8 yrs; 57.9 ± 9.4 ml·min-1·kg-1 peak oxygen uptake performed one session of high intensity 4x4 min intervals (HIIT at 90-95% peak power output, each interval separated by 3 min of active recovery, and one high volume session (HVT consisting of a constant load exercise for 90 min at 60% peak power output. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min, and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126 and VEGF mRNA.Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre values, whereas HIIT showed no significant influence on the miRNAs compared to pre values. VEGF mRNA significantly increased during and after HIIT (d1, 30`, 60`, 180` and HVT (d3, 0`, 60`. Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126 in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.

  17. Circulating Vascular Endothelial Growth Factor (VEGF Levels in Advanced Stage Cancer Patients Compared to Normal Controls and Diabetes Mellitus Patients with Critical Ischemia

    Directory of Open Access Journals (Sweden)

    Yoka H. Kusumanto

    2007-01-01

    Full Text Available Anti-angiogenic therapy is emerging as a valuable tool in the treatment of patients with cancer. As VEGF is a central target in anti-angiogenic therapy, its levels in the circulation might be relevant in selecting tumor types or patients likely to respond to this treatment. Additional VEGF has been recognized as a key factor in the pathogenesis of diabetic retinopathy. Recently anti-angiogenic therapy has been advocated in this situation. We measured VEGF levels in whole blood in 42 patients with high grade (n = 26 and low grade (n = 16 end stage cancer, and in 28 healthy controls and 37 patients with diabetes related vascular disease. Only 2/26 patients in the group of high grade cancer had signifi cantly elevated VEGF levels, 1/16 in the low grade group and 1/28 in the healthy control group. In contrast, in 10/37 diabetic patients the mean VEGF levels were significantly elevated compared to the other groups. The mean level in these diabetic patients was significantly elevated compared to the other groups. These data indicate the limitation of the use of circulating VEGF levels as a potential selection criterion for anti-angiogenic therapy in cancer patients and suggest further studies into its application in the management of diabetic complications.

  18. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.

    Science.gov (United States)

    Rudzitis-Auth, Jeannette; Nenicu, Anca; Nickels, Ruth M; Menger, Michael D; Laschke, Matthias W

    2016-08-01

    The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis. PMID:27315780

  19. Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Preis, Sarah R; Beiser, Alexa;

    2015-01-01

    .04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (β for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2...... remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03. CONCLUSIONS: Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations...

  20. Innovative Flow Cytometry Allows Accurate Identification of Rare Circulating Cells Involved in Endothelial Dysfunction

    Science.gov (United States)

    Boraldi, Federica; Bartolomeo, Angelica; De Biasi, Sara; Orlando, Stefania; Costa, Sonia; Cossarizza, Andrea; Quaglino, Daniela

    2016-01-01

    Introduction Although rare, circulating endothelial and progenitor cells could be considered as markers of endothelial damage and repair potential, possibly predicting the severity of cardiovascular manifestations. A number of studies highlighted the role of these cells in age-related diseases, including those characterized by ectopic calcification. Nevertheless, their use in clinical practice is still controversial, mainly due to difficulties in finding reproducible and accurate methods for their determination. Methods Circulating mature cells (CMC, CD45-, CD34+, CD133-) and circulating progenitor cells (CPC, CD45dim, CD34bright, CD133+) were investigated by polychromatic high-speed flow cytometry to detect the expression of endothelial (CD309+) or osteogenic (BAP+) differentiation markers in healthy subjects and in patients affected by peripheral vascular manifestations associated with ectopic calcification. Results This study shows that: 1) polychromatic flow cytometry represents a valuable tool to accurately identify rare cells; 2) the balance of CD309+ on CMC/CD309+ on CPC is altered in patients affected by peripheral vascular manifestations, suggesting the occurrence of vascular damage and low repair potential; 3) the increase of circulating cells exhibiting a shift towards an osteoblast-like phenotype (BAP+) is observed in the presence of ectopic calcification. Conclusion Differences between healthy subjects and patients with ectopic calcification indicate that this approach may be useful to better evaluate endothelial dysfunction in a clinical context. PMID:27560136

  1. 后循环缺血患者血管病变DSA分析%Analysis of Vascular Lesions in Patients with Posterior Circulation Ischemia by Digital Subtraction Angiography(DSA)

    Institute of Scientific and Technical Information of China (English)

    韩晶

    2013-01-01

    Objective:To discuss the posterior circulation ischemia and cerebral blood supply artery lesions by digital subtraction angiography (DSA) inspection.Methods:All 76 patients with posterior circulation ischemia in DSA vascular imaging examination,and the lesion vessels for comprehensive analysis.Results:90.79%patients with vascular lesions, according to the classification of the vascular lesions parts, the most common is posterior circulation lesions with 47 cases (68.11%), in which 32 cases with posterior circulation occlusion or stenosis only,8 cases with other lesions only (including dissection,hypoplasia,variation,tortuosity etc.),7 cases with posterior circulation occlusion or stenosis and other lesion,followed by 9 cases (13.03%)with anterior and posterior circulation lesions, 8 cases (11.59%)with anterior circulation lesions,5 cases (7.24%)with the start of subclavian artery lesions and posterior circulation lesions. The common sites of posterior circulation vascular occlusion/narrow were vertebral artery first segment (V1) (42lesions, 60%), intracranial VA(V4) (7 lesions, 10%),basilar artery(BA) (6 lesions, 8.57%). Conclusion:PCI mainly involving the posterior circulation artery lesions, the common sites of posterior circulation vascular occlusions or narrows were extracranial VA,intracranial VA and BA, steal syndrome and posterior circulation vessel variation is one of the causes of PCI, so DSA is the gold standard in the diagnosis of posterior circulation ischemic vascular lesions.%目的:通过数字减影全脑血管造影(DSA)检查探讨后循环缺血与供血脑动脉病变的关系。方法:对76例后循环缺血患者进行DSA全脑血管造影检查,并对其病变血管进行综合性分析。结果:90.79%患者存在血管病变,按血管病变部位分类最常见的是单纯后循环血管病变47例(68.11%),其次是前后循环均受累9例(13.03%),单纯前循环病变8例(11.59%),锁骨下动脉起始处病变伴后循环病变5例(7

  2. Comparative analysis of circulating endothelial progenitor cells in age-related macular degeneration patients using automated rare cell analysis (ARCA and fluorescence activated cell sorting (FACS.

    Directory of Open Access Journals (Sweden)

    Emil Anthony T Say

    Full Text Available BACKGROUND: Patients with age-related macular degeneration (ARMD begin with non-neovascular (NNV phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs, defined as CD34(+VEGR2(+ using traditional fluorescence activated cell sorting (FACS, are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA, a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion. METHODS: We obtained peripheral venous blood samples in 23 subjects with NNV-ARMD or treatment naïve NV-ARMD. Strict criteria were used to exclude subjects with known angiogenic diseases to minimize confounding results. Blood samples were analyzed in masked fashion in two separate laboratories. EPCs were independently enumerated using ARCA and FACS within 24 hours of blood sample collection, and p<0.2 was considered indicative of a trend for this proof of concept study, while statistical significance was established at 0.05. RESULTS: We measured levels of CD34(+VEGFR2(+ EPCs suggestive of a trend with higher values in patients with NV compared to NNV-ARMD (p = 0.17 using ARCA. Interestingly, CD34(+VEGR2(+ EPC analysis using FACS did not produce similar results (p = 0.94. CONCLUSIONS: CD34(+VEGR2(+ may have predictive value for EPC enumeration in future ARCA studies. EPC measurements in a small sample

  3. The CMV early enhancer/chicken beta actin (CAG) promoter can be used to drive transgene expression during the differentiation of murine embryonic stem cells into vascular progenitors

    DEFF Research Database (Denmark)

    Alexopoulou, Annika N; Couchman, John R; Whiteford, James

    2008-01-01

    BACKGROUND: Mouse embryonic stem cells cultured in vitro have the ability to differentiate into cells of the three germ layers as well as germ cells. The differentiation mimics early developmental events, including vasculogenesis and early angiogenesis and several differentiation systems are being...... used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult....... RESULTS: CCE mouse embryonic stem cells were differentiated on collagen type IV for 4-5 days, Flk1+ mesodermal cells were sorted and replated either on collagen type IV in the presence of VEGFA to give rise to endothelial cells and smooth muscle cells or in collagen type I gels for the formation...

  4. Endothelial progenitor cells with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    KONG Xiao-dong; ZHANG Yun; LIU Li; SUN Ning; ZHANG Ming-yi; ZHANG Jian-ning

    2011-01-01

    Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer's disease (AD).Endothelial progenitor cells (EPCs) have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.Methods A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, rianjin Medical University. Consecutive patients with newly diagnosed AD (n=30),patients with vascular dementia (VaD, n=34), and healthy elderly control subjects with normal cognition (n=40) were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.Results There were no significant statistical differences of clinical data in AD, VaD and control groups (P >0.05). The patients with AD showed decreased CD34-positive (CD34+) or CD133-positive (CD133+) levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34+CD133+ EPCs(CD34 and CD133 double positive endothelial progenitor cells) than the control subjects (P <0.05). In the patients with AD, a lower CD34+CD133+ EPCs count was independently associated with a lower Mini-Mental State Examination score (r=0.514, P=0.004). Patients with VaD also showed a significant decrease in CD34+CD133+ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than

  5. Progenitor Cells and Podocyte Regeneration

    Science.gov (United States)

    Shankland, Stuart J.; Pippin, Jeffrey W.; Duffield, Jeremy S.

    2014-01-01

    The very limited ability of adult podocytes to proliferate in vivo is clinically significant because: podocytes form a vascular barrier which is functionally critical to the nephron; podocyte hypoplasia is a characteristic of disease; and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density is almost certainly reliant on regeneration by podocyte progenitors. However such putative progenitors have remained elusive until recently. In this review we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing ‘progenitor’ markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo with evidence from animal models suggesting a more limited role of PEC-capacity to serve as podocyte progenitors in adults. We will highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles including those which produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis. PMID:25217270

  6. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia

    Directory of Open Access Journals (Sweden)

    Andrea Piccin

    2015-11-01

    Full Text Available Introduction: Circulating microparticles (MP have been described in sickle cell anaemia (SCA; however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC, free protein S (PS, nitric oxide (NO, endothelin-1 (ET-1 and adrenomedullin (ADM in a large cohort of paediatric patients. Method: A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU therapy; 15 on transfusion; 17 controls (HbAA of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV, CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor, CD201 (endothelial PC receptor, CD62E, CD36 (TSP-1, CD47 (TSP-1 receptor, CD31 (PECAM, CD144 (VE-cadherin. Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured. Results: Total MP AV was lower in crisis (1.26×106 ml−1; 0.56–2.44×106 and steady state (1.35×106 ml−1; 0.71–3.0×106 compared to transfusion (4.33×106 ml−1; 1.6–9.2×106, p0.9, p<0.05 between total numbers of AV-positive MP (MP AV and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05 (platelet activation marker, and also a lower correlation between percentage of MP expressing CD201 (%MP CD201 and %MP CD14 (R=0.627, p<0.001. %MP CD201 was higher in crisis (11.6% compared with HbAA (3.2%, p<0.05; %MP CD144 was higher in crisis (7.6% compared with transfusion (2.1%, p<0.05; %CD14 (0.77% was higher in crisis compared with transfusion (0.0%, p<0.05 and steady state (0.0%, p<0.01; MP CD14 was detectable in a higher number of samples (92% in crisis compared with the rest (40%; %MP CD235a was higher in crisis (17.9% compared with transfusion (8.9%, HU (8.7% and steady state (9.9%, p<0.05; %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L−1 (0.31–0

  7. Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Jia-Yin Sun

    2013-05-01

    Full Text Available OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05 and better left ventricle function (p<0.01. CONCLUSIONS: The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients.

  8. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    Science.gov (United States)

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release. PMID:27454856

  9. Characterization of a Distinct Population of Circulating Human Non-Adherent Endothelial Forming Cells and Their Recruitment via Intercellular Adhesion Molecule-3

    OpenAIRE

    Appleby, Sarah L.; Cockshell, Michaelia P.; Pippal, Jyotsna B.; Thompson, Emma J.; Barrett, Jeffrey M.; Katie Tooley; Shaundeep Sen; Wai Yan Sun; Randall Grose; Ian Nicholson; Vitalina Levina; Ira Cooke; Gert Talbo; Lopez, Angel F.; Bonder, Claudine S.

    2012-01-01

    Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+) popul...

  10. Reduced circulating endothelial progenitor cells is a risk factor of coronary slow flow%循环内皮祖细胞与冠状动脉慢血流的关系

    Institute of Scientific and Technical Information of China (English)

    李全忠; 韩金杰; 陈华; 莫新玲; 夏中华; 钱宗杰

    2013-01-01

    Objective To explore if reduced number of circulating endothelial progenitor cells (EPCs) is a risk factor for patients with coronary slow flow (CSF).Methods Thirty patients with CSF and 30 age and gender matched control subjects with normal coronary angiography were included in the study.Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation and plated on fibronectin-coated culture dishes.EPCs were characterized as adherent cells double positive for DiI-AcLDLuptake and lectin-binding by converted fluorescence microscope (× 200).Results Smoking,diabetes mellitus,hypertension and the levels of plasma lipoprotein profile were similar between the two groups (all P > 0.05).The number of EPCs was significantly lower in patients with CSF compared with control subjects (35.7 ± 5.9 vs.53.2 ± 5.9,P < 0.01).TIMI frame counts was correlated with circulating EPCs number (OR =0.424,95% CI 0.358-0.621,P < 0.01) and not associated with gender,age,smoking,diabetes mellitus,hypertension and the levels of plasma lipoprotein profile.Conclusion Decreased circulating EPCs is an independent risk factor for CSF.%目的 观察冠状动脉慢血流(CSF)患者循环内皮祖细胞(EPC)数量与CSF之间的关系,探讨CSF发病的可能机制.方法 选择冠状动脉造影结果正常和CSF患者各30例,采用密度梯度离心法从外周血获取单个核细胞,通过FITC标记荆豆凝集素和DiI标记的乙酰化低密度脂蛋白双染色、倒置荧光显微镜(200倍视野)鉴定EPC并对EPC进行计数.应用t检验和卡方检验比较两组患者临床资料的差异,并采用logistic回归分析法对相关因素进行分析.结果 两组患者的年龄、性别、高血压、糖尿病、吸烟史所占比例及血脂水平差异均无统计学意义,CSF患者外周血EPC数量明显少于正常对照组(35.7±5.9比53,2±5.9,t=10.3,P<0.01).logistic回归分析显示,性别、年龄、吸烟史、高血压史、糖尿病

  11. Effect of exercise on markers of vascular health in renal transplant recipients.

    Science.gov (United States)

    Piťha, J; Králová Lesná, I; Stávek, P; Mahrová, A; Racek, J; Sekerková, A; Teplan, V; Štollová, M

    2015-01-01

    The cornerstone of cardiovascular risk management is lifestyle intervention including exercise which could exert favorable impact also in renal transplant recipients. Nevertheless, reliable assessment of the effect of lifestyle interventions is complicated and the available data in this population are not consistent. The aim of the study was to evaluate the effect of physical activity on selected laboratory markers of vascular health including circulating stem cells, endothelial progenitor cells, microparticles, and plasma asymmetric dimethyl arginine in renal transplant recipients. Nineteen men and 7 women were recruited in 6-month program of standardized and supervised exercise. Control group consisted of 23 men and 13 women of similar age and body mass index not included into the program. One year after the transplantation, the main difference between intervention and control group was found in the change of endothelial progenitor cells (p=0.006). Surprisingly, more favorable change was seen in the control group in which endothelial progenitor cells significantly increased compared to the intervention group. The explanation of this finding might be a chronic activation of reparative mechanisms of vascular system in the population exposed to multiple risk factors which is expressed as relatively increased number of endothelial progenitor cells. Therefore, their decrease induced by exercise might reflect stabilization of these processes.

  12. Effect of Perindopril on Vascular Endothelial Function and Endothelial Progenitor Cells of Patients with Coronary Artery Disease%培哚普利对冠心病患者血管内皮功能及EPCs水平的影响

    Institute of Scientific and Technical Information of China (English)

    刘微

    2016-01-01

    目的:观察培哚普利对冠心病患者血管内皮功能及内皮祖细胞( EPCs)水平的影响。方法将90例冠心病患者随机分为对照组和研究组,每组45例,对照组患者给予常规对症支持治疗,研究组患者在对照组治疗的基础上加用培哚普利治疗,治疗12 w后,比较两组患者肱动脉內皮依赖性血管舒张功能( FMD)及外周血EPCs水平变化。结果与治疗前比较,两组患者治疗后肱动脉FMD和EPCs明显升高,差异具有统计学意义( P<0.05)。与对照组治疗后比较,研究组治疗后肱动脉FMD和EPCs显著升高,差异具有统计学意义( P<0.05)。结论培哚普利在冠心病患者临床治疗中能较好的促进内皮祖细胞动员和血管内皮功能改善,值得临床推广应用。%Objective To observe the effect of perindopril on the endothelial progenitor cells ( EPCs) and vascular endothelial function of patients with coronary artery disease. Methods 90 patients with coronary artery disease were randomly divided into control group and research group, with 45 cases in each group. The control group was given conventional therapy, while the other group re-ceived perindopril apart from the regular treatment. After 12 weeks’ treatment, the change of the flow-mediated-dilation ( FMD) func-tion of the brachial artery and EPCs from the peripheral blood of the two groups was compared. Results Compared with the indexes before treatment, the FMD and EPCs of the two groups after treatment increased obviously, with statistically significant difference ( P<0. 05). Compared with the control group, the FMD and EPCs of the research group after treatment increased significantly, and the difference was statistically significant (P<0. 05). Conclusion Perindopril can help mobilize EPCs and improve the endothelial func-tion in the treatment for patients with coronary artery disease, which makes it worthy of application.

  13. Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia

    Science.gov (United States)

    Dong, Yu; Sun, Qi; Liu, Teng; Wang, Huanyuan; Jiao, Kun; Xu, Jiahui; Liu, Xin; Liu, Huirong; Wang, Wen

    2016-01-01

    In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that

  14. Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia.

    Science.gov (United States)

    Dong, Yu; Sun, Qi; Liu, Teng; Wang, Huanyuan; Jiao, Kun; Xu, Jiahui; Liu, Xin; Liu, Huirong; Wang, Wen

    2016-01-01

    In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that

  15. 血管内皮祖细胞在人工血管移植后内皮化中的作用及其机制%Roles and mechanisms of endothelial progenitor cells in the post-transplant tacho-endothelialization of vascular prosthesis

    Institute of Scientific and Technical Information of China (English)

    李杰; 吕伟明; 李晓曦

    2007-01-01

    OBJECTIVE:To review the relationship between endothelial progenitor cells and the re-endothelialization of vascular prosthesis in order to find out some effective ways to solve the most frequent complications of asotransplantation,thrombogenesis and intima hyperplasia.DATA SOURCES:A computer-based online search was conducted to identify articles related to endothelial progenitor cells and the re-endothelialization of vascular prosthesis published in Pubmed,Ovid and MD Consult database from January 2000 to December 2006 using the key words of "endothelial progenitor cells,vascular prosthesis,endothelialization".Meanwhile,CNKI database was searched for related papers published between January 2000and December 2006,the keywords were "endothelial progenitor cells,vascular prosthesis,endothelialization" in Chinese.STUDY SELECTION:The literatures included all the related papers about the roles of endothelial progenitor cells in the re-endothelialization of vascular prosthesis.Inclusive criteria:the study types were randomized controlled trials,drug stress test and clinical drug effect test; the samples were both human and animals.Exclusive criteria:Reviews and literatures without controls were excluded.DATA EXTRACTION:Totally 115 related literatures were collected,and 24 were accorded with the inclusive criteria.The excluded were 91 papers of reviews and repeated trials or drug effect studies.DATA SYNTHESIS:These related literatures,including not only animal experiments but also clinical detections,analyzed the relationship between endothelial progenitor cells and the re-endothelialization of vascular prosthesis and correlative promoting mechanisms.CONCLUSION:It is concluded that endothelial progenitor cells play an important role in the endothelialization after vascular prosthesis is grafted in vivo.%目的:阐述近年来国内外关于血管内皮祖细胞促进人工血管移植后内皮化进程的机制,以期为l临床解决人工血管移植后血栓形成和内

  16. The effect of moderate-intensity acute aerobic exercise duration on the percentage of circulating CD31+ cells in lymphocyte population

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    Mariani Santosa

    2016-04-01

    Full Text Available Background: The increasing number of circulating CD31+ endothelial progenitor cells is one of the important factors for maintaining vascular homeostasis. Exercise will effectively increase the number of circulating CD31+ endothelial progenitor cells. This study aims to determine the effect of moderate-intensity acute aerobic exercise duration on the percentage of circulating CD31+ cells in untrained healthy young adult subjects.Methods: This study was an experimental study. Untrained healthy volunteers (n=20 performed ergocycle at moderate-intensity (64–74% maximum heart rate for 10 minutes or 30 minutes. Immediately before and 10 minutes after exercise, venous blood samples were drawn. The percentage of CD31+ cells in peripheral blood was analyzed using flow cytometry. Data was statistically analyzed using student t-test.Results: There were no significant differences in the mean percentage of circulating CD31+ cells before and after exercise for 10 minutes and 30 minutes (p>0.05. However, there was a different trend in the percentage of circulating CD31+ cells after exercise for 10 minutes and 30 minutes. In the 10 minutes duration, 50% of subjects showed increase. Whereas in the 30 minutes duration, 80% of subjects showed increase.Conclusion: The percentage of circulating CD31+ cells before and after exercise for 10 minutes was not different compared to 30 minutes. However, data analysis shows that majority of subjects (80% had increased in the percentage of circulating CD31+ cells after 30 minutes exercise.

  17. Effects of Hemodynamic Forces on the Vascular Differentiation of Stem Cells: Implications for Vascular Graft Engineering

    Science.gov (United States)

    Diop, Rokhaya; Li, Song

    Although the field of vascular tissue engineering has made tremendous advances in the past decade, several complications have yet to be overcome in order to produce biocompatible small-diameter vascular conduits with long-term patency. Stem cells and progenitor cells represent potential cell sources in the development of autologous (or allogeneic), nonthrombogenic vascular grafts with mechanical properties comparable to native blood vessel. However, a better understanding of the effects of mechanical forces on stem cells and progenitor cells is needed to properly utilize these cells for tissue engineering applications. In this chapter, we discuss the current understanding of the effects of hemodynamic forces on the differentiation and function of adult stem cells, embryonic stem cells, and progenitor cells. We also review the use of stem cells and progenitor cells in vascular graft engineering.

  18. Differentiation of Murine Bone Marrow-Derived Smooth Muscle Progenitor Cells Is Regulated by PDGF-BB and Collagen.

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    Clifford Lin

    Full Text Available Smooth muscle cells (SMCs are key regulators of vascular disease and circulating smooth muscle progenitor cells may play important roles in vascular repair or remodelling. We developed enhanced protocols to derive smooth muscle progenitors from murine bone marrow and tested whether factors that are increased in atherosclerotic plaques, namely platelet-derived growth factor-BB (PDGF-BB and monomeric collagen, can influence the smooth muscle specific differentiation, proliferation, and survival of mouse bone marrow-derived progenitor cells. During a 21 day period of culture, bone marrow cells underwent a marked increase in expression of the SMC markers α-SMA (1.93 ± 0.15 vs. 0.0008 ± 0.0003 (ng/ng GAPDH at 0 d, SM22-α (1.50 ± 0.27 vs. 0.005 ± 0.001 (ng/ng GAPDH at 0 d and SM-MHC (0.017 ± 0.004 vs. 0.001 ± 0.001 (ng/ng GAPDH at 0 d. Bromodeoxyuridine (BrdU incorporation experiments showed that in early culture, the smooth muscle progenitor subpopulation could be identified by high proliferative rates prior to the expression of smooth muscle specific markers. Culture of fresh bone marrow or smooth muscle progenitor cells with PDGF-BB suppressed the expression of α-SMA and SM22-α, in a rapidly reversible manner requiring PDGF receptor kinase activity. Progenitors cultured on polymerized collagen gels demonstrated expression of SMC markers, rates of proliferation and apoptosis similar to that of cells on tissue culture plastic; in contrast, cells grown on monomeric collagen gels displayed lower SMC marker expression, lower growth rates (319 ± 36 vs. 635 ± 97 cells/mm2, and increased apoptosis (5.3 ± 1.6% vs. 1.0 ± 0.5% (Annexin 5 staining. Our data shows that the differentiation and survival of smooth muscle progenitors are critically affected by PDGF-BB and as well as the substrate collagen structure.

  19. [The role of circulating immune complexes and the status of argyrophilic membranes of the vascular walls in the development of brain edema in patients with meningococcal meningoencephalitis].

    Science.gov (United States)

    Gebesh, V V; Iarosh, O A

    1991-01-01

    Based on clinical and immunological examinations of 60 patients with MME and 30 normal persons, the dynamics of the blood CIC content was studied depending on the time and gravity of the disease. The discovered changes in argyrophilic membranes of the vascular walls are determined to a considerable measure by the pathogenic action of CIC on microvessels, which entails the derangement of blood-brain barrier function and contributes to the development of acute purulent meningitis. PMID:1647627

  20. Vascular Cures

    Science.gov (United States)

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  1. Expression of platelet-bound stromal-cell derived factor-1 (SDF-1) and number of CD34(+) progenitor cells in patients with congestive heart failure.

    Science.gov (United States)

    Jorbenadze, Rezo; Schleicher, Erwin; Bigalke, Boris; Stellos, Konstantinos; Gawaz, Meinrad

    2014-01-01

    Platelet-bound stromal cell-derived factor-1 (SDF-1) plays a crucial role in attachment of circulating CD34(+) progenitor cells to the vascular wall, facilitating tissue healing after injury. However there is no evidence about expression of platelet-bound SDF-1 in patients with congestive heart failure (CHF). The aim of our study was to evaluate expression of platelet-bound SDF-1 and number of CD34(+) progenitor cells in patients with CHF. Forty-eight patients with idiopathic dilated cardiomyopathy (DCM) and 61 patients with ischaemic cardiomyopathy (ICM) were consecutively enrolled into the study. Blood taken from 109 consecutive patients was studied for surface expression of platelet-bound SDF-1 and number of CD34(+) progenitor cells by flow cytometry. The highest expression of platelet-bound SDF-1 was observed in patients with severe impairment of left ventricular systolic function compared with patients with mild or moderate impairment of left ventricular systolic function (mild vs. moderate vs. severe impairment of left ventricular systolic function: MFI ± SD: 35.6 ± 34 vs. 101.45 ± 73 vs. 124.86 ± 86.7, Kruskal-Wallis p number of CD34(+) progenitor cells was the highest in severe impairment of left ventricular systolic function (mild vs. moderate vs. severe impairment of left ventricular systolic function: mean ± SD: 260.4 ± 177.5 vs. 580.7 ± 340.5 vs. 640.82 ± 370.6, Kruskal-Wallis p number of circulating CD34(+) progenitor cells (r = 0.454, p number of CD34(+) cells were higher in patients with DCM compared with patients with ICM (p cells are especially increased in patients with severe impairment of left ventricular systolic function in CHF.

  2. Effects on cerebral circulation of decimeter wave therapy and variable magnetic field in patients with hemiparesis of vascular and traumatic origin

    Energy Technology Data Exchange (ETDEWEB)

    Strelkova, N.I.; Gavrilkov, A.T.; Dyuzhilova, N.F.; Strel' tsova, Ye.N.

    1981-08-01

    Both the artherosclerotic process in the case of cerebrovascular accident and cerebral trauma lead to impairment of cerebral hemodynamics, blood and spinal fluid circulation, macroscopic and microscopic disturbances. Electromagnetic waves in the decimeter range (decimeter waves - DMW) and a variable magnetic field (VMF) were used to treat these processes. Treatment was delivered directly to the region of the cerebral lesion, on the basis of the penetrating capacity of DMW and VMF to a relatively great depth (7 to 9 and 4 to 7 cm, respectively). Results of these treatments are discussed.

  3. 循环血液中内皮祖细胞在充血性心力衰竭患者中的表达%Expression of endothelial progenitor cells with the blood circulation in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    余东彪; 吴继雄

    2012-01-01

    目的 研究内皮祖细胞在充血性心力衰竭患者中的表达情况,并进一步研究其与心衰严重程度的相关性.方法 选择心衰患者96例(纽约心功能分级:Ⅰ级22例,Ⅱ级25例,Ⅲ级26例,Ⅳ级23例)及健康正常人25例(对照组),以CD34、CD45为表面标记,用流式细胞仪测量外周血中的内皮祖细胞数,并同时测量脑钠肽(BNP).结果 心衰患者较对照组BNP水平升高(P<0.01),且心衰的严重程度与BNP呈正相关;在心功能Ⅰ级、Ⅱ级心衰患者中,内皮祖细胞较健康对照组明显升高(P<0.01);心功能Ⅲ级、Ⅳ级患者较健康对照组降低(P<0.05或<0.01).结论 内皮祖细胞在心衰患者中呈现一个双向性改变,即在心衰晚期阶段外周血内皮祖细胞表达较对照组明显下降,而在心衰早期阶段较对照组明显升高,提示受损的内皮祖细胞招募可能参与严重心衰患者的病理生理过程.%Objective To investigate the pattern of endothelial progenitor cells during congestive heart failure and their correlation with the severity. Methods 96 patients with heart failure (NYHA Class Ⅰ: 22 cases, Ⅱ: 25 cases, Ⅲ: 26 cases, Ⅳ: 23 cases) and 25 cases of normal control group were measured CD34, CD45, peripheral blood endothelial progenitor cells number with flow cytometric and simultaneously measured brain natriuretic peptide (BNP) level. Results The heart failure patients increased significantly BNP levels than the control group, and the severity of the heart failure with BNP was positively correlated. Endothelial progenitor cells were increased in NYHA Class I and NYHA Class Ⅱ compared with that in controls ( P < 0. 01 ). Endothelial progenitor cells were significantly decreased in NYHA Class Ⅳ and NYHA Class Ⅲ compared with that in controls (P < 0.05 or P < 0.01). Conclusions Endothelial progenitor cells in the heart failure patients show a biphasic response, with elevation and depression in the early and

  4. Early Vascular Damage in Young Women with DM-1 and Its Relation to Anti-Müllerian Hormone: A Cross-Sectional Study

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    Annelien C. de Kat

    2016-01-01

    Full Text Available Vascular function is suggested to be associated with ovarian reserve, but the relationship with microvascular function has never been studied. In this cross-sectional pilot study, the relationship of microvascular damage markers with AMH was studied in premenopausal women. Twenty-two regularly cycling women with type 1 diabetes (DM-1 and a reference group of 20 healthy regularly cycling women were included, from whom blood was drawn in the early follicular phase of the menstrual cycle. The main outcome was the correlation between circulating progenitor cells (CPCs, markers for early vascular damage, and AMH, a marker for ovarian reserve. Secondary endpoints for early vascular impairment were circulating angiogenic cells and additional biomarkers. Median AMH levels were 2.2 µg/L [1.2–3.5] in the DM-1 group and 2.1 µg/L [0.85–3.8] in the reference group. CPCs were significantly decreased in women with DM-1; 1204±537 CD34+/CD45dim cells were counted in the DM-1 group, compared to 2264±1124 in the reference group. CPCs and other markers of early vascular damage were not correlated with AMH levels in a multivariable analysis. These results underscore previous findings of early vascular damage in DM-1 and suggest that there may not be a relationship between vascular function and ovarian reserve. Trial Registration. This trial is registered with Clinicaltrials.gov NCT01665716.

  5. The role of endothelial progenitor cells in transient ischemic attack patients for future cerebrovascular events

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    Rokhsareh Meamar

    2016-01-01

    Full Text Available Background: The role of endothelial progenitor cells (EPCs in the maintenance of vascularization following ischemic brain after experimental stroke has been established. Accordingly, in this study, we evaluated the role of circulating EPCs in transient ischemic attack (TIA patients for future cerebrovascular (CV events. Materials and Methods: The level of circulating EPCs (staining markers: CD34, CD309 were determined using flow cytometry at 24 h after TIA in thirty consecutive patients. The EPCs level was also evaluated once in thirty healthy volunteers. Over a period of 12 months, all patients were evaluated by an experienced neurologist for recurrent TIA, stroke or death induced by CV disorders. Results: Circulating EPCs increased in patients group following the first attack of TIA when compared with controls. By analysis of covariance, cardiovascular event history, hyperlipidemia, and statin therapy remained significant independent predictors of EPCs. The mean (standard deviation duration of follow-up was 10.5 (3.1 months (range, 2–12 months. During follow-up, a total of three patients died due to CV accident and four patients experienced again recurrent TIA. By analyzing data with Cox regression, EPC did not predict the future CV events in TIA patients. Conclusion: Increased incidence of future CV events did not occur in those patients with elevated EPCs in the first attack of TIA. The significant predicting factors of EPCs were cardiovascular event history, hyperlipidemia, and statin therapy.

  6. Endothelial Progenitor Cells Predict Cardiovascular Events after Atherothrombotic Stroke and Acute Myocardial Infarction. A PROCELL Substudy.

    Directory of Open Access Journals (Sweden)

    Elisa Cuadrado-Godia

    Full Text Available The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI or atherothrombotic stroke (AS. We were interested in the prognostic role of endothelial progenitor cells (EPC and circulating endothelial cells (CEC.Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA, stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT, atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis.During follow-up, 19 patients (12.66% had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death. Vascular events were associated with age (P = 0.039, carotid IMT≥0.9 (P = 0.044, and EPC count (P = 0.041 in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22-87.34, P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21-13.95, P = 0.023].Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk.

  7. Progenitor cells in arteriosclerosis: good or bad guys?

    Science.gov (United States)

    Campagnolo, Paola; Wong, Mei Mei; Xu, Qingbo

    2011-08-15

    Accumulating evidence indicates that the mobilization and recruitment of circulating or tissue-resident progenitor cells that give rise to endothelial cells (ECs) and smooth muscle cells (SMCs) can participate in atherosclerosis, neointima hyperplasia after arterial injury, and transplant arteriosclerosis. It is believed that endothelial progenitor cells do exist and can repair and rejuvenate the arteries under physiologic conditions; however, they may also contribute to lesion formation by influencing plaque stability in advanced atherosclerotic plaque under specific pathologic conditions. At the same time, smooth muscle progenitors, despite their capacity to expedite lesion formation during restenosis, may serve to promote atherosclerotic plaque stabilization by producing extracellular matrix proteins. This profound evidence provides support to the hypothesis that both endothelial and smooth muscle progenitors may act as a double-edged sword in the pathogenesis of arteriosclerosis. Therefore, the understanding of the regulatory networks that control endothelial and smooth muscle progenitor differentiation is undoubtedly fundamental both for basic research and for improving current therapeutic avenues for atherosclerosis. We update the progress in progenitor cell study related to the development of arteriosclerosis, focusing specifically on the role of progenitor cells in lesion formation and discuss the controversial issues that regard the origins, frequency, and impact of the progenitors in the disease.

  8. PULMONARY CIRCULATION AT EXERCISE

    OpenAIRE

    R. Naeije; CHESLER, N

    2012-01-01

    The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associ...

  9. [The best of vascular medicine in 2005].

    Science.gov (United States)

    Mounier-Vehier, C; Stephan, D; Becker, F; Beregi, J P; Haulon, S; Kownator, S; Marboeuf, P; Sevestre, M A; Constans, J

    2006-01-01

    It is illusory to think that one year is long enough to establish all the truths that will guide our clinical practice in vascular medicine. On the contrary, one year was long enough to contradict what the preceding twelve months had set out to demonstrate. Consequently, promising trials in the treatment of abdominal aortic aneurysms by endoprostheses have been the object of contradictory debate with regards to the long-term benefits. In fundamental research, circulating progenitors of endothelial cells have been shown to be a marker of atherosclerosis, but is it a better marker than LDL-cholesterol values? The demonstration that these progenitors are of value in the treatment of essential ischaemia of the lower limbs is awaited. Finally, ximelagatran, a direct thrombin antagonist, seemed to have all the qualities of an ideal anticoagulant: easy to use, safe... until the report of raised hepatic enzymes, the clinical relevance of which remains to be determined. In the good news section: the Systolic Pressure Index, an unquestioned marker of arterial disease. Its reduction was known to be correlated with the prevalence of cardiovascular complications. However, it has now been shown that an increase in the index is also associated with cardiovascular complications, a real U-shaped curve. Renal arterial stenosis should be considered in patients with left ventricular failure presenting with flash pulmonary oedema. In the absence of cardiac pathology, BNP would seem to be a good biological marker of haemodynamically significant renal arterial stenosis. Finally, should superficial femoral artery stenosis be treated by an active stent. To date, there is no formal proof. PMID:16479963

  10. Obstructive sleep apnea and endothelial progenitor cells

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    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

  11. 血管内皮生长因子和雌二醇促进血管内皮祖细胞分化生成血管的对比研究%Comparative study of vascular endothelial growth factor and estradiol in promoting endothelial progenitor cells differentiation and generation blood vessels

    Institute of Scientific and Technical Information of China (English)

    董勇; 李文志; 辛毅; 孙智

    2013-01-01

    Objective To compare the ability of vascular endothelial growth factor (VEGF) and estradiol in promoting endothelial progenitor cells differentiation and generation blood vessels under common doses. Methods To isolate and culture human peripheral blood EPCs first, then to mixe with the matrigel and transplante to the lower abdomens of nine nude mice.to divide the nine nude mice into three groups according to a random grouping, to inject VEGF.estradiol and saline at a regular time,to observe and record the growing status of vascular tissue regularly.to draw the vascular tissue after six weeks, to observe the organizational structure by HE staining, then contrast with the groups. Results The vascular tissue volume groups injected of drugs have significant difference with the groups injected of saline.they have bigger volume to contrast the groups injected of saline, but he vascular tissue volume between the groups injected of drugs is no significant difference. By drawning HE staining, the vascular tissues have proliferational mussy blood vessels.The vascular density of the groups injected of drugs is significantly greater than the groups injected of saline, but he vascular density between the groups injected of drugs is small. Conclusion VEGF and estradiol can promote EPCs differentiation and generation blood vessels.their respective promoting EPCs differentiation and generation blood vessels potency is no significant difference under common doses.%目的:对比研究常规剂量下血管内皮生长因子(VEGF)和雌二醇对血管内皮祖细胞(EPCs)分化生成血管的促进作用.方法:分离培养人外周血EPCs,与基质胶混匀后注射到9只裸鼠双侧下腹部,另设2只注射等体积培养液与基质胶的混合液.将9只注射细胞的裸鼠随机分为3组,每组分别定期局部注射VEGF、雌二醇,生理盐水,定期观察记录血管组织块的生长状况.移植6周后取材,测量计算血管组织块的体积、HE染色观察血管

  12. Comparison of modified chandler, roller pump, and ball valve circulation models for in vitro testing in high blood flow conditions: application in thrombogenicity testing of different materials for vascular applications.

    Science.gov (United States)

    van Oeveren, Wim; Tielliu, Ignace F; de Hart, Jurgen

    2012-01-01

    Three different models, a modified Chandler loop, roller pump, and a new ball valve model (Hemobile), were compared with regard to intrinsic damage of blood components and activation of platelets. The Hemobile was used for testing of polymer tubes. High flow was not possible with the Chandler loop. The roller pump and the Hemobile could be adjusted to high flow, but he pump induced hemolysis. Platelet numbers were reduced in the roller pump and Chandler loop (P testing vascular graft materials, and allowed different circuits circulated simultaneously at 37°C. ePTFE, Dyneema Purity UHMWPE fiber and PET fiber based tubes, all showed hemolysis below 0.2% and reduced platelet count and function. Binding of fibrin and platelets was higer on PET, inflammatory markers were lowest on Dyneema Purity UHMWPE. We concluded that the Hemobile minimally affects blood and could be adjusted to high blood flows, simulating arterial shear stress. The Hemobile was used to measure hemocompatibility of graft material and showed Dyneema Purity UHMWPE fiber in many ways more hemocompatible than ePTFE and PET. PMID:22649450

  13. Circulating endothelial cells in cardiovascular disease.

    Science.gov (United States)

    Boos, Christopher J; Lip, Gregory Y H; Blann, Andrew D

    2006-10-17

    Quantification of circulating endothelial cells (CECs) in peripheral blood is developing as a novel and reproducible method of assessing endothelial damage/dysfunction. The CECs are thought to be mature cells that have detached from the intimal monolayer in response to endothelial injury and are a different cell population to endothelial progenitor cells (EPCs). The EPCs are nonleukocytes derived from the bone marrow that are believed to have proliferative potential and may be important in vascular regeneration. Currently accepted methods of CEC quantification include the use of immunomagnetic bead separation (with cell counting under fluorescence microscopy) and flow cytometry. Several recent studies have shown increased numbers of CECs in cardiovascular disease and its risk factors, such as unstable angina, acute myocardial infarction, stroke, diabetes mellitus, and critical limb ischemia, but no change in stable intermittent claudication, essential hypertension, or atrial fibrillation. Furthermore, CEC quantification at 48 h after acute myocardial infarction has been shown to be an accurate predictor of major adverse coronary events and death at both 1 month and 1 year. This article presents an overview of the pathophysiology of CECs in the setting of cardiovascular disease and a brief comparison with EPCs. PMID:17045885

  14. [Vascular parkinsonism].

    Science.gov (United States)

    Marxreiter, F; Winkler, J

    2016-07-01

    Parkinsonism may result from cerebral vascular disorders that feature white matter lesions and small vessel pathology. Vascular Parkinsonism typically presents as lower body Parkinsonism with predominant gait impairment. Urinary incontinence and cognitive decline are additional features of the disease. There is a considerable overlap between vascular Parkinsonism and vascular dementia. We review the clinical characteristics of vascular Parkinsonism and discuss the current treatment approaches, as well as the role of brain imaging for the diagnostic workup. . PMID:27299942

  15. Literature Study of Vascular Dementia Treated with Nourishing Kidney and Activating Blood Circulation for Medication Rules%补肾活血法治疗血管性痴呆用药规律文献研究

    Institute of Scientific and Technical Information of China (English)

    伍大华; 祝皓

    2011-01-01

    目的 通过对补肾活血法为主治疗血管性痴呆(VD)内服方用药的统计,总结归纳出补肾活血治疗VD的用药规律,为临床用药及相关研究提供依据.方法 以频数分析为主统计1995-2010年中国知网数据库、维普数据库、万方数据库中以补肾活血法为主治疗VD的论文,归纳总结补肾活血法治疗VD的用药规律.结果 在药物使用频次上,补肾活血法使用药物频数大于50的为何首乌、川芎、丹参、枸杞、熟地黄、水蛭.在药物药性方面,用药以温性最多,其积分为1.377,其余依次为寒、微温、微寒等.在用药药味方面,苦、甘、辛三昧积分明显高于其他诸味,分别为3.608、3.929、3.295.结论 何首乌、枸杞、熟地黄为补肾药中的核心药物,川芎、丹参、水蛭为活血药中的核心药物.补肾活血用药温性药物多于寒性,药味以苦、甘、辛为主.%Objective: To summarize the law of evidence to general regularity by studying the TCM literature of vascular dementia(VD) mainly explore typification of statistics and to offers reference for clinical medication rules. Methods: The frequency statistic was by prossessing databases of CNKI,VIP,WAN FANG during 1994-2010 which were mainly related to the treatment with nourishing kidney and activating blood circulation of TCM literature of VD and summarizing the medication rules of VD. Results: The frequency of Shou wu,River xiong,Salvia miltiorrhiza,Chinese wolfberry.Ripe dihuang,and Leeches used in nourishing kidney and activating blood circulation were more than 50. Drug of temperature nature was used mostly which integral was 1.377. Using frequency of bitter,grape and michael essien were obviously higher than the other which integral respectively was 3.929, 3.608,3.295. Conclusion: For VD, Shou wu,Chinese wolfberry and Ripe dihuang are anchor drugs in the treatment of ourishing kidney.River xiong,Salvia miltiorrhiza and Leeches are anchor drugs in the treatment

  16. Effects of Angiotensin Ⅱ on Vascular Endothelial Growth Factor Expression in Early Endothelial Progenitor Cells from Human Peripheral Blood%血管紧张素Ⅱ对外周血早期内皮祖细胞血管内皮生长因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    孙文文; 任国庆; 汪奕斌; 张浩

    2011-01-01

    Aim To investigate the effect of angiotensin Ⅱ on vascular endothelial growth factor expression of early endothelial progenitor cells. Methods Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7 days of culture, several groups of attached cells were incubated with angiotensin Ⅱ (to make a series of concentrations: 10-3 mol/L, 10 -5 mol/L, 10-7 mol/L vehicle control for 24 h), angiotensin Ⅱ + valsartan, angiotensin Ⅱ + PD123319. The cells were observed under inverted microscope, and characterized as adherent cells double positive for DiL DL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. The early endothelial progenitor cells were further documented by demonstrating the expression of cell markers with flow cytometry. Enzyme-linked immunospecific assay (ELISA) were used to assess vascular endothelial growth factor expression. Results Our data indicated that angiotensin Ⅱ can significantly increase the vascular endothelial growth factor expression, with a maximum at 10-3 mol/L after 24 hours (P <0. 05); These effects can be attenuated by pre-treatment with valsartan but not PD123319.Conclusion It is suggested that angiotensin Ⅱ induces vascular endothelial growth factor protein secretion via the angiotensin Ⅱ receptor-1 but not angiotensin Ⅱ receptor-2.%目的 观察血管紧张素Ⅱ对外周血早期内皮祖细胞血管内皮生长因子表达的影响.方法 密度梯度离心法获取外周血单个核细胞,培养7天,收集贴壁细胞,随机分对照组、血管紧张素Ⅱ各浓度 (10-3 mol/L、10-5 mol/L、10-7 mol/L) 组、血管紧张素Ⅱ+缬沙坦组、血管紧张素Ⅱ+ PD123319组.多波长激光共聚焦显微镜鉴定FITC标记荆豆凝集素Ⅰ和 DiI标记的乙酰化低密度脂蛋白双染色阳性为早期内皮祖细胞,流式细胞仪

  17. Fabrication of endothelial progenitor cell capture surface via DNA aptamer modifying dopamine/polyethyleneimine copolymer film

    Science.gov (United States)

    Li, Xin; Deng, Jinchuan; Yuan, Shuheng; Wang, Juan; Luo, Rifang; Chen, Si; Wang, Jin; Huang, Nan

    2016-11-01

    Endothelial progenitor cells (EPCs) are mainly located in bone marrow and circulate, and play a crucial role in repairmen of injury endothelium. One of the most promising strategies of stents designs were considered to make in-situ endothelialization in vivo via EPC-capture biomolecules on a vascular graft to capture EPCs directly from circulatory blood. In this work, an EPC specific aptamer with a 34 bases single strand DNA sequence was conjugated onto the stent surface via dopamine/polyethyleneimine copolymer film as a platform and linker. The assembled density of DNA aptamer could be regulated by controlling dopamine percentage in this copolymer film. X-ray photoelectron spectroscopy (XPS), water contact angle (WCA) and fluorescence test confirmed the successful immobilization of DNA aptamer. To confirm its biofunctionality and cytocompatibility, the capturing cells ability of the aptamer modified surface and the effects on the growth behavior of human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs) were investigated. The aptamer functionalized sample revealed a good EPC-capture ability, and had a cellular friendly feature for both EPC and EC growth, while not stimulated the hyperplasia of SMCs. And, the co-culture experiment of three types of cells confirmed the specificity capturing of EPCs to aptamer modified surface, rather than ECs and SMCs. These data suggested that this aptamer functionalized surface may have a large potentiality for the application of vascular grafts with targeted endothelialization.

  18. Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells.

    Science.gov (United States)

    Zhao, Jing; Mitrofan, Claudia-Gabriela; Appleby, Sarah L; Morrell, Nicholas W; Lever, Andrew M L

    2016-01-01

    Late outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo expansion before they could provide a practical cell therapy and it is currently unclear if they would home and engraft to an injury site. Using an in vitro flow system we studied LO-EPC under simulated injury conditions including EC activation, ischaemia, disrupted EC integrity, and exposed basement membrane. Perfused LO-EPC adhered to discontinuous EC paracellularly at junctional regions between adjacent cells under shear stress 0.7 dyn/cm(2). The interaction was not adhesion molecule-dependent and not enhanced by EC activation. LO-EPC expressed high levels of the VE-Cadherin which may explain these findings. Ischaemia reperfusion injury decreased the interaction with LO-EPC due to cell retraction. LO-EPC interacted with exposed extracellular matrix (ECM) proteins, fibronectin and vitronectin. The interaction was mediated by integrins α5β3, αvβ1, and αvβ3. This study has demonstrated that an injured local environment presents sufficient adhesive signals to capture flow perfused LO-EPC in vitro and that LO-EPC have properties consistent with their potential role in vascular repair. PMID:27413378

  19. Fetal Circulation

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Fetal Circulation Updated:Jul 8,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  20. Effect of Chinese Drugs for Promoting Blood Circulation and Eliminating Blood Stasis on Vascular Endothelial Growth Factor Expression in Rabbits with Glucocorticoid-induced Ischemic Necrosis of Femoral Head

    Institute of Scientific and Technical Information of China (English)

    QI Zhen-xi; CHEN Lei

    2009-01-01

    Objective:To probe into the mechanism of Chinese drugs for promoting blood circulation and eliminating blood stasis in the prevention and treatment of glueocorticoid-induced ischemic necrosis of femoral head.Methods: Thirty New Zealand adult white rabbits were randomly divided into a normal control group (n=5)and a model group (n=25). Hydroxyprednisone acetate was intramuscularly administered to the rabbits in the model group in a dosage of 7.5 mg/kg, twice per week for 6 weeks, to induce ischemic necrosis of femoral head and normal saline of the equal volume was intramuscularly administered to the rabbits in the normal control group, twice per week for 6 weeks. Then, the 5 rabbits from the normal control group and 5 rabbits selected randomly from the model group were sacrificed and the changes in histopathology and the expression of Vascular Endothelial Growth Factor (VEGF) were observed. The other 20 rabbits in the model group were randomly divided into the treatment group 1 and the treatment group 2, and the control group 1 and the control group 2, 5 rabbits in every group. Taohong Siwu Tang (桃红四物汤 Decoction of Four Drugs with Addition of Peach Kernel and Safflower) was orally administered to the rabbits in the treatment group 1 and the treatment group 2 in a dosage of 7 ml/kg, once daily and normal saline of the equal volume was orally administered to the rabbits in the control groupl and the control group, 2 once daily. After 10 weeks the rabbits in the treatment group 1 and the control group 1 were sacrificed and after 13 weeks the rabbits in the treatment group 2 and the control group 2 were sacrificed, and the expression of VEGF was detected in these rabbits. Results: The expression of VEGF was significantly enhanced in rabbits of the model group as compared with the normal control group (P<0.01), and gradually reduced with the lapse of time. The expression of VEGF in the control groups was significantly reduced as compared with the treatment

  1. Effect of Low Level Ionizing Radiation on Endothelial Progenitor Cells in Atherosclerotic Patients with Lower Limb Ischemia

    International Nuclear Information System (INIS)

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality throughout the developed world (Williamson et al., 2012). Coronary artery disease (CAD) or atherosclerotic heart disease is a chronic life-threatening disease, which characterized by reducing blood supply to the heart as a result of the accumulation of atheromatous plaques within the walls of the arteries supplying the myocardium. Progressive atherosclerosis in the coronary arteries may lead to intimal thickening and eventual artery occlusion. Coronary artery occlusion can cause acute myocardial ischemia as a result of reduced oxygen supply or increased oxygen demand (Luthje and Andreas, 2008). Convincing evidence indicates that atherosclerosis is associated with endothelial dysfunction at the early stage of the disease process (Chiang et al., 2012). The endothelium is a dynamic cell layer that represents a physiological barrier between circulating blood and the surrounding tissues. Impaired endothelial function is a critical event in the initiation of atherosclerotic plaque development and thus may lead to vasoconstriction, vascular smooth muscle proliferation, hypercoagulability, thrombosis, and eventually, adverse cardiovascular events (Berger and Lavie, 2011). Asahara et al., (1997) described endothelial progenitor cells (EPC) in human peripheral blood. EPC are immature endothelial circulating cells mobilized from the bone marrow. These cells are involved in Introduction and aim of the work repairing the damaged endothelium and in facilitating neovascularization after ischemia (Rouhl et al., 2008). The role of EPC in health and disease is not understood completely. Most studies of healthy subjects and patients with coronary artery disease (CAD) report that the number and function of circulating EPC decrease with age and with the presence of classical vascular risk factors (Fadini et al., 2007). Recent studies suggested that EPCs play an important role in the risk of vascular

  2. GRB Progenitors and Environment

    OpenAIRE

    Lazzati, Davide

    2005-01-01

    The study and knowledge of the environment of Gamma-Ray Bursts is of great interest from many points of view. For high redshift (z>0.5) events, the structure of the ambient medium is one of the best indicators of the nature and properties of the progenitor. It also tells us about the last stages of the pre-explosion evolution of the progenitor. In addition, it is interesting in its own as a sample of the interstellar medium in a high redshift galaxy. Measures of the density and structure of t...

  3. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  4. Enhancing endothelial progenitor cell for clinical use

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Circulating endothelial progenitor cells (EPCs) havebeen demonstrated to correlate negatively with vascularendothelial dysfunction and cardiovascular risk factors.However, translation of basic research into the clinicalpractice has been limited by the lack of unambiguousand consistent definitions of EPCs and reduced EPCcell number and function in subjects requiring them forclinical use. This article critically reviews the definitionof EPCs based on commonly used protocols, their valueas a biomarker of cardiovascular risk factor in subjectswith cardiovascular disease, and strategies to enhanceEPCs for treatment of ischemic diseases.

  5. 紫绀型先天性心脏病病人循环内皮祖细胞的数量及功能变化%Changes of circulating endothelial progenitor cells in patients with cyanotic congenital heart diseases

    Institute of Scientific and Technical Information of China (English)

    刘哲亮; 吴忠仕; 胡建国; 陈勇; 胡野荣; 李伟

    2008-01-01

    Objective To investigate alterations of endothelial progenitor cells (EPCs) from peripheral blood in patients with cyanotic congenital heart diseases.Methods 20 ml venous blood was obtained from patients with tetralogy of Fallot (TOF) and ventricular septal defect (VSD).The mononuclear cells were isolated by Ficoll density gradient centrifugation and cultured in Medium 199 containing 20 % fetal bovine serum (FBS) and bovine pituitary exrtract (BPE) for expansion and differentiation.The expression of EPC-specific antigens on cell surface,such as CD133,KDR,CD34,CD31 and vWF were analyzed by immunocytochemistry after 10 days.Cultured cells were further characterized by uptake of Dil-AcLDL,lectin staining by UEA-1,and flow cytometry for quantification of CD133+/KDR+ cells. Transmission electron microscopy was used to identify distinctive organelles of EPCs,namely immature mitochondria and weibel-Palade bodies.Modified Boyden chamber assay and MTT assay was used to measure the migration and proliferation of EPCs.The adhesion assay was performed by replating on fibronectin-coated dishes and then quantifying the number of adherent cells.Results The number of EPCs was significantly increased in patients with TOF compared with that of control subjects [Colony numbers (14.7±3.1) vs.8.2±1.3]/×100 field,DiI-AcLDL+/UEA-I+ (72.2±9.7) vs.(51.2±3.8)/×200 field,CD133+/KDR+ cells (0.66±0.20)% vs.(0.18±0.08)%,P<0.01).The functional activity of EPCs such as proliferation [Optical Density (OD) value 0.34±0.02 vs. 0.27±0.01],migration[(140.6±9.2) vs.(91.8±8.6)/×200 field)] and adhesive capacity [(149.0±11.6)vs.(112.6±7.0)/×200 field)] was also significantly higher in patients with TOF.Conclusion EPC quantity and functional activity are significantly increased in patient with cyanotic congenital heart diseases.%目的 探讨紫绀型先天性心脏病病人外周血内皮祖细胞(endothelial progenitor cell,EPC)的数量及功能特点.方法 选取法洛四联症

  6. The effects of smoking on levels of endothelial progenitor cells and microparticles in the blood of healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Fariborz Mobarrez

    Full Text Available BACKGROUND: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs and circulating microparticles (MPs following the smoking of one cigarette by young, healthy intermittent smokers. MATERIALS AND METHODS: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. RESULTS: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin. CD144 (VE-cadherin or HMGB1 release did not significantly change during active smoking. CONCLUSION: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.

  7. What "helps" tumors evade vascular targeting treatment?

    Institute of Scientific and Technical Information of China (English)

    SI Zhi-chao; LIU Jie

    2008-01-01

    Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were "angiogenesis", "vascular targeting treatment" and "endothelial progenitor cells".Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells.Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature's resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor.Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included.This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment.Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.

  8. Association among circulating endothelial progenitor cells, insulin resistance and severity of coronary lesions in patients with coronary artery disease%冠心病患者胰岛素水平与内皮祖细胞及冠状动脉病变的相关性

    Institute of Scientific and Technical Information of China (English)

    钱德慧; 黄岚; 赵晓辉; 周音频; 崔斌; 宋耀明; 李爱民; 付晓岚

    2008-01-01

    目的 探讨冠心病患者不同胰岛素水平与循环内皮祖细胞(EPC)数量、功能及冠状动脉病变程度的关系并探讨相关临床意义.方法 69例经选择性冠状动脉造影证实的冠心病患者,按胰岛素水平高低分为胰岛素抵抗(IR)组和胰岛素敏感(IS)组,另设25例健康对照者.采集研究对象外周血以激酶插入区域受体(KDR)和CD133双阳性为循环EPC标记行流式细胞分析,同时采血进行EPC的分离培养,7 d后鉴定并检测增殖及迁移能力,将各组的一般临床资料,循环EPC数量、迁移、增殖能力指标、稳态模型胰岛素抵抗指数(HOMA-IR)及冠状动脉病变Gensini评分进行统计学分析.结果 IR组循环EPC数量明显少于IS组[(0.34±0.08)‰比(0.47±0.09)‰,P<0.01],HOMA-IR自然对数与循环EPC数量呈负相关(r=-0.291,P=0.01),循环EPC数量与Gensini评分呈负相关(r=-0.3984,P=0.006).IR组的增殖能力和迁移能力均低于IS组减弱(P<0.05).结论 冠心病患者血清胰岛素水平与循环EPC数量呈负相关.循环EPC数量及功能与冠状动脉病变程度呈负相关;IR或高胰岛素血症可能部分通过损害循环EPC的数量及功能,从而影响冠状动脉病变程度.%Objective To investigate the correlation between the number and activity of circulating endothelial progenitor cells (EPCs), insulin resistance and severity of coronary lesions in patients with coronary artery disease (CAD). Methods Patients with coronary angiography evidenced CAD were divided in insulin resistance group ( IR, n = 25 ) and insulin sensitive group ( IS, n = 44) according to insulin level, 25 health volunteers served as control. Circulating EPCs were marked as KDR/CD133<'+ cells via fluorescence- activated cell sorter analysis. EPCs were also isolated from peripheral blood and cultured in vitro for 7 days, identified by DiI-acLDL uptake and lectin staining methods. EPCs migration activities were determined by modified Boyden chamber assay

  9. Vascular smooth muscle cells for use in vascular tissue engineering obtained by endothelial-to-mesenchymal transdifferentiation (EnMT) on collagen matrices

    NARCIS (Netherlands)

    Krenning, Guido; Moonen, Jan-Renier A. J.; van Luyn, Marja J. A.; Harmsen, Martin C.

    2008-01-01

    The discovery of the endothelial progenitor cell (EPC) has led to an intensive research effort into progenitor cell-based tissue engineering of (small-diameter) blood vessels. Herein, EPC are differentiated to vascular endothelial cells and serve as the inner lining of bioartificial vessels. As yet,

  10. 规律运动增加内皮祖细胞数量和功能改善衰老血管弹性*****☆%Regular exercise improves age-related decline in arterial elasticity by enhancing number and activity of endothelial progenitor cells

    Institute of Scientific and Technical Information of China (English)

    杨震; 张媛媛; 夏文豪; 罗初凡; 陈龙; 靳亚飞; 欧志君; 廖新学; 陶军

    2013-01-01

    progenitor cel s as an independent predictor of decreased brachial-ankle pulse wave velocities. Regular exercise-induced enhanced number and activity of circulating endothelial progenitor cel s attenuates age-related decline in arterial elasticity, indicating that the modulation of exercise on circulating endothelial progenitor cel s may be the mechanism underlying exercise-exhibited protection against age-related vascular injury.

  11. Analysis of the Changes in Circulation of Sub-dermal Vascular Network Flap Made from Flap-type Skin Avulsion and Replanted to Origin Site%皮瓣型皮肤撕脱伤修成暴露真皮下血管网皮瓣回植创面的血循环变化分析

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To find out the characteristics of the changes in circulation of sub-dermal vascular network flap made from flap-type skin avulsion Injury and replanted to origin site. Method: Pig skin avulsion model was used in this experiment. Flap's blood circulation was monitored and surviving flap length measured. Result. Flap blood circulation was markedly improved. Conclusion: Sub-dermal vascular network flap made from skin avulsion flap and replanted to origin site can improved the survival length of the flap.%目的:了解皮肤撕脱伤修成暴露真皮下血管网皮瓣回植创面的血循环变化特点和对皮瓣成活的影响。方法:以猪为实验对象,制作皮肤撕脱伤模型,观察皮瓣的血循环变化和成活情况。结果:将撕脱瓣修成暴露真皮下血管网的皮瓣再回植,可以使皮瓣血循环显著改善。结论:将撕脱瓣修成暴露真皮下血管网的皮瓣再回植,可以使皮瓣成活长度显著增加。

  12. Nearshore circulation

    NARCIS (Netherlands)

    Battjes, J.A.; Sobey, R.J.; Stive, M.J.F.

    1990-01-01

    Shelf circulation is driven primarily by wind- and tide-induced forces. It is laterally only weakly constrained so that the geostrophic (Coriolis) acceleration is manifest in the response. Nearshore circulation on the other hand is dominated by wave-induced forces associated with shallow-water. wave

  13. Neural progenitor cells regulate microglia functions and activity.

    Science.gov (United States)

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  14. The Vascular Microenvironment and Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Tracy Frech

    2010-01-01

    Full Text Available The role of the vascular microenvironment in the pathogenesis Systemic Sclerosis (SSc is appreciated clinically as Raynaud's syndrome with capillary nail bed change. This manifestation of vasculopathy is used diagnostically in both limited and diffuse cutaneous subsets of SSc, and is thought to precede fibrosis. The degree of subsequent fibrosis may also be determined by the vascular microenvironment. This paper describes why the vascular microenvironment might determine the degree of end-organ damage that occurs in SSc, with a focus on vascular cell senescence, endothelial progenitor cells (EPC including multipotential mesenchymal stem cells (MSC, pericytes, and angiogenic monocytes. An explanation of the role of EPC, pericytes, and angiogenic monocytes is important to an understanding of SSc pathogenesis. An evolving understanding of the vascular microenvironment in SSc may allow directed treatment.

  15. Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

    Institute of Scientific and Technical Information of China (English)

    DONG Fang; HA Xiao-qin

    2010-01-01

    Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was "endothelial progenitor cells".Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.

  16. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells.

    Science.gov (United States)

    Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S; Felldin, Ulrika; He, Xiaobing; Nichane, Massimo; Yang, Henry; Bu, Lei; Li, Ronald A; Lim, Bing; Chien, Kenneth R

    2016-03-08

    Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1(+) vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo.

  17. 内皮祖细胞与动脉瘤的发生与发展%Endothelial progenitor cells and occurrence and development of aneurysm

    Institute of Scientific and Technical Information of China (English)

    梁超杰; 闵国文; 郭庚

    2013-01-01

    背景:内皮祖细胞具有修复血管损伤及预测早期血管损伤程度的功能。这一生物学特性被引入到动脉瘤的研究之中,为动脉瘤的发生、发展、早期诊断及治疗提供新的思路。  目的:从内皮祖细胞的生物学特性(增殖、迁移、黏附、衰老)及其在外周循环血中的数量和内皮祖细胞用于动脉瘤的相关临床实验资料进行总结分析。  方法:以“内皮祖细胞、前体细胞、动脉瘤、干细胞”,“ endothelial progenitor cel s、precursor、aneurysm、stem cel”为检索词,应用计算机检索期刊万方数据库、中国知网(CNKI)数据库及Pubmed数据库、Springer数据库,Sciencedirect数据库、Ovid数据库。排除与动脉瘤研究无关或内容重复的文献,对纳入文献做进一步分析。  结果与结论:动脉瘤患者的外周循环血中内皮祖细胞数量减少并伴有功能受损。在接受动脉瘤的相关治疗后内皮祖细胞数量上升。内皮祖细胞可早期预测动脉瘤的发生、发展和破裂,也可作为一种治疗方法去阻止动脉瘤的发生。如何将内皮祖细胞广泛的应用到临床当中去预防和防止动脉瘤的发生发展是亟待解决的问题。%BACKGROUND:Endothelial progenitor cells can be used to repair vascular injuries and predict severity of early vascular injuries. These biological characteristics have been recommended to the research of aneurysm, which provide new ideas for studying the occurrence, expansion and early staging diagnosis of aneurysm. OBJECTIVE:To elaborate the effects of endothelial progenitor cells on the aneurysm in the clinical trials based on the biological characteristics of endothelial progenitor cells, including proliferation, migration, adherence and senescence. METHODS:A computer-based search of Wanfang, CNKI, Springer, PubMed, ScienceDirect, and Ovid was performed using the keywords of“endothelial progenitor cells

  18. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  19. Stem cells and progenitor cells in renal disease.

    Science.gov (United States)

    Haller, Hermann; de Groot, Kirsten; Bahlmann, Ferdinand; Elger, Marlies; Fliser, Danilo

    2005-11-01

    Stem cells and progenitor cells are necessary for repair and regeneration of injured renal tissue. Infiltrating or resident stem cells can contribute to the replacement of lost or damaged tissue. However, the regulation of circulating progenitor cells is not well understood. We have analyzed the effects of erythropoietin on circulating progenitor cells and found that low levels of erythropoietin induce mobilization and differentiation of endothelial progenitor cells. In an animal model of 5/6 nephrectomy we could demonstrate that erythropoietin ameliorates tissue injury. Full regeneration of renal tissue demands the existence of stem cells and an adequate local "milieu," a so-called stem cell niche. We have previously described a stem cell niche in the kidneys of the dogfish, Squalus acanthus. Further analysis revealed that in the regenerating zone of the shark kidney, stem cells exist that can be induced by loss of renal tissue to form new glomeruli. Such animal models improve our understanding of stem cell behavior in the kidney and may eventually contribute to novel therapies. PMID:16221168

  20. Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: A case-control pilot study

    NARCIS (Netherlands)

    O. van Oostrom (Olivia); D.P.V. de Kleijn (Dominique); J.O. Fledderus (Joost); M. Pescatori (Mario); A. Stubbs (Andrew); A. Tuinenburg (Attie); S.K. Lim (Sai Kiang); M.C. Verhaar (Marianne)

    2009-01-01

    textabstractBackground: Endothelial progenitor cells play an important role in vascular wall repair. Patients with type 1 diabetes have reduced levels of endothelial progenitor cells of which their functional capacity is impaired. Reduced nitric oxide bioavailability and increased oxidative stress p

  1. Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Hyung Joon; Seo, Ha-Rim [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Jeong, Hyo Eun [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Choi, Seung-Cheol; Park, Jae Hyung; Yu, Cheol Woong; Hong, Soon Jun [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Chung, Seok [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Lim, Do-Sun, E-mail: dslmd@kumc.or.kr [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Two distinct vascular progenitor cells are induced from adult peripheral blood. • ECFCs induce vascular structures in vitro and in vivo. • SMPCs augment the in vitro and in vivo angiogenic potential of ECFCs. • Both cell types have synergistic therapeutic potential in ischemic hindlimb model. - Abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.

  2. Inhibition of Prostaglandin Transporter (PGT Promotes Perfusion and Vascularization and Accelerates Wound Healing in Non-Diabetic and Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Zhongbo Liu

    Full Text Available Peripheral ischemia, resulting from diminished arterial flow and defective local vascularization, is one of the main causes of impaired wound healing in diabetes. Vasodilatory prostaglandins (PGs, including PGE2 and PGI2, regulate blood flow in peripheral tissues. PGs also stimulate angiogenesis by inducing vascular endothelial growth factor. However, PG levels are reduced in diabetes mainly due to enhanced degradation. We hypothesized that inhibition of the prostaglandin transporter (PGT (SLCO2A1, which mediates the degradation of PGs, would increase blood flow and stimulate vascularization, thereby mitigating peripheral ischemia and accelerating wound healing in diabetes. Here we report that inhibiting PGT with intravenously injected PGT inhibitor, T26A, increased blood flow in ischemic hind limbs created in non-diabetic rats and streptozotocin induced diabetic rats. Systemic, or combined with topical, T26A accelerated closure of cutaneous wounds. Immunohistochemical examination revealed that inhibition of PGT enhanced vascularization (marked by larger numbers of vessels formed by CD34+ cells, and accelerated re-epithelialization of cutaneous wounds. In cultured primary human bone marrow CD34+ cells and human epidermal keratinocytes (HEKs either inhibiting or silencing PGT increased migration in both cell lines. Thus PGT directly regulates mobilization of endothelial progenitor cells (EPCs and HEKs, which could contribute to PGT-mediated vascularization and re-epithelialization. At the molecular level, systemic inhibition of PGT raised circulating PGE2. Taken together, our data demonstrate that PGT modulates arterial blood flow, mobilization of EPCs and HEKs, and vascularization and epithelialization in wound healing by regulating vasodilatory and pro-angiogenic PGs.

  3. From progenitor to afterlife

    CERN Document Server

    Chevalier, R A

    2006-01-01

    The sequence of massive star supernova types IIP (plateau light curve), IIL (linear light curve), IIb, IIn (narrow line), Ib, and Ic roughly represents a sequence of increasing mass loss during the stellar evolution. The mass loss affects the velocity distribution of the ejecta composition; in particular, only the IIP's typically end up with H moving at low velocity. Radio and X-ray observations of extragalactic supernovae show varying mass loss properties that are in line with expectations for the progenitor stars. For young supernova remnants, pulsar wind nebulae and circumstellar interaction provide probes of the inner ejecta and higher velocity ejecta, respectively. Among the young remnants, there is evidence for supernovae over a range of types, including those that exploded with much of the H envelope present (Crab Nebula, 3C 58, 0540--69) and those that exploded after having lost most of their H envelope (Cas A, G292.0+1.8).

  4. Vascular progenitor cells in the development of transplant arteriopathy

    NARCIS (Netherlands)

    Hillebrands, JL; Rienstra, H; Onuta, G; Rozing, J

    2005-01-01

    Although advances in graft procurement, preservation, matching and immunosuppression have all contributed to today's outstanding short-term graft survival rates after solid organ transplantation, similar success has not been achieved in preventing chronic transplant dysfunction (CTD) and extending l

  5. 冠心病患者血浆循环miR-126的表达及其对血管内皮细胞的影响%Plasma circulating miR-126 in patients with coronary artery heart disease and its effect on vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    郑志伟; 劳海燕; 余细勇; 陈纪言; 林秋雄; 麦丽萍; 钟诗龙

    2011-01-01

    AIM: To investigate the role of plasma circulating miR - 126 and miR - 16 in the patients with coronary artery heart disease and to explore the influence of miR - 126 on vascular endothelial cells. METHODS: Plasma total RNA was isolated from 52 patients with stable coronary artery disease and 52 healthy volunteers. The circulating miR -126 and miR -16 in those people were detected using specific primers. Endothelial cell line EA. Hy926 was transfected with a miR - 126 inhibitor, and total RNA of the cells was isolated 30 h after transfection to detect the expression level of vascular endothelial growth factor ( VEGF ). RESULTS: The expression of plasma circulating miR - 126 was significantly decreased in the patients with coronary artery heart disease compared with healthy controls ( P 0. 05 ). The expression of VEGF in the endothelial cell line EA. Hy926 transfected with miR - 126 inhibitor was 2.08 times higher than that in negative control cells 30 h after transfection ( P 0.05);(2)内皮细胞株EA.hy926中miR-126被抑制后,血管内皮生长因子的表达为对照组的2.08倍(P<0.05).结论:血浆循环miR-126在冠心病患者表达下降,血浆循环miR-16在人群中的表达较稳定;miR-126通过负性调节血管内皮生长因子的表达,对血管内皮细胞产生调节作用.

  6. Circulation economics

    DEFF Research Database (Denmark)

    Ingebrigtsen, Stig; Jakobsen, Ove

    2006-01-01

    presupposes a perspective integrating economic, natural and cultural values. Third, to organize the interplay between all stakeholders we introduce an arena for communicative cooperation. Originality/value - The paper concludes that circulation economics presupposes a change in paradigm, from a mechanistic...

  7. Endothelial progenitor cell down-regulation in a mouse model of Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    LIU Jun-feng; DU Zhong-dong; CHEN Zhi; LU Dun-xiang; LI Li; GUAN Yun-qian; WAN Sui-gui

    2012-01-01

    Background Cardiovascular complications of Kawasaki disease (KD) are a common cause of heart disease in pediatric populations.Previous studies have suggested a role for endothelial progenitor cells (EPCs) in coronary artery lesions associated with KD.However,long-term observations of EPCs during the natural progression of this disorder are lacking.Using an experimental model of KD,we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.Methods To induce KD,C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE; phosphate buffered saline used as control vehicle).Study groups included:group A (14 days following LCWE injection),group B (56 days following LCWE injection) and group C (controls).Numbers of circulating EPCs (positively staining for both CD34 and FIk-1 while staining negative for CD45) were evaluated using flow cytometry.Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis.In vitro EPC proliferation,adhesion and migration were assessed.Results The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms.Numbers of circulating EPCs decreased significantly in the KD models (groups A and B) compared to controls ((0.017±0.008)% VS.(0.028±0.007)%,P<0.05 and (0.016±0.007)% vs.(0.028±0.007)%,P <0.05).Proliferative,adhesive and migratory properties of EPCs were markedly impaired in groups A and B.Conclusion Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair,resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.

  8. The adventitia: essential regulator of vascular wall structure and function.

    Science.gov (United States)

    Stenmark, Kurt R; Yeager, Michael E; El Kasmi, Karim C; Nozik-Grayck, Eva; Gerasimovskaya, Evgenia V; Li, Min; Riddle, Suzette R; Frid, Maria G

    2013-01-01

    The vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. It is the most complex compartment of the vessel wall and is composed of a variety of cells, including fibroblasts, immunomodulatory cells (dendritic cells and macrophages), progenitor cells, vasa vasorum endothelial cells and pericytes, and adrenergic nerves. In response to vascular stress or injury, resident adventitial cells are often the first to be activated and reprogrammed to influence the tone and structure of the vessel wall; to initiate and perpetuate chronic vascular inflammation; and to stimulate expansion of the vasa vasorum, which can act as a conduit for continued inflammatory and progenitor cell delivery to the vessel wall. This review presents the current evidence demonstrating that the adventitia acts as a key regulator of vascular wall function and structure from the outside in. PMID:23216413

  9. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    Science.gov (United States)

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  10. Multifactorial treatment increases endothelial progenitor cells in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Reinhard, H; Jacobsen, P Karl; Lajer, Marianne;

    2010-01-01

    Endothelial progenitor cells (EPC) augment vascular repair and neovascularisation. Patients with type 2 diabetes have reduced EPC and increased risk of cardiovascular disease (CVD), which is reduced by multifactorial intervention. Our aim, therefore, was to evaluate in type 2 diabetic patients...

  11. Estradiol increases hematopoietic stem and progenitor cells independent of its actions on bone

    NARCIS (Netherlands)

    Illing, Anett; Liu, Peng; Ostermay, Susanne; Schilling, Arndt; de Haan, Gerald; Krust, Andree; Amling, Michael; Chambon, Pierre; Schinke, Thorsten; Tuckermann, Jan P.

    2012-01-01

    Hematopoietic stem and progenitor cells reside in vascular and endosteal niches in the bone marrow. Factors affecting bone remodeling were reported to influence numbers and mobilization of hematopoietic stem cells. We therefore analyzed the effects of estradiol acting anabolic on bone integrity. Her

  12. Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors

    DEFF Research Database (Denmark)

    Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger;

    2016-01-01

    ) and thymus that is located within the vascular niche surrounding PDPN-PDGFRβ+/α-Esam-1+ITGA7+ pericytes. CD34+ adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ...

  13. Progenitors of type Ia supernovae

    CERN Document Server

    Maeda, Keiichi

    2016-01-01

    Natures of progenitors of type Ia Supernovae (SNe Ia) have not yet been clarified. There has been long and intensive discussion on whether the so-called single degenerate (SD) scenario or the double degenerate (DD) scenario, or anything else, could explain a major population of SNe Ia, but the conclusion has not yet been reached. With rapidly increasing observational data and new theoretical ideas, the field of studying the SN Ia progenitors has been quickly developing, and various new insights have been obtained in recent years. This article aims at providing a summary of the current situation regarding the SN Ia progenitors, both in theory and observations. It seems difficult to explain the emerging diversity seen in observations of SNe Ia by a single population, and we emphasize that it is important to clarify links between different progenitor scenarios and different sub-classes of SNe Ia.

  14. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

    Science.gov (United States)

    Chakravarthy, Harshini; Beli, Eleni; Navitskaya, Svetlana; O'Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B; Busik, Julia V

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  15. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

    Directory of Open Access Journals (Sweden)

    Harshini Chakravarthy

    Full Text Available Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs. We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  16. 多灶性后循环缺血患者的病灶分布与血管形态异常及近期预后分析%Multiple infarcts in the posterior circulation: infarcts distribution, vascular malformation and prognosis

    Institute of Scientific and Technical Information of China (English)

    肖力; 何俐; 郑洪波; 杨觅; 杨雪; 王玉才; 张亚男

    2009-01-01

    目的 观察多灶性后循环缺血患者的病灶分布和血管形态异常的特点,评估患者出院时的近期预后及其与病灶分布和血管形态的关系.方法 对34例经过MR/所证实的多灶性后循环缺血患者行主动脉弓及全脑血管DSA,全面分析病灶分布及血管形态异常的特点;同时对患者出院时的近期预后用改良Rankin分级(MRS)评分表进行评估,分析病灶分布及血管形态异常与近期预后的关系.结果 多灶性后循环缺血患者最常被累及的部位是脑桥(22例),最常被累及的区段是中段+远段(12例);34例患者中有26例(76.5%)DSA显示出血管形态异常,最常被累及的动脉是椎动脉起始段(14例)和颅内段(13例)及基底动脉(7例);出院时7例患者(20.6%)存在预后不良,其中6例(17.6%)为重度残疾,1例(2.9%)死亡.近中远段同时受累和基底动脉受累的患者表现出预后不良.结论 血管形态异常是多灶性后循环缺血的重要病理基础和致病因素,病灶区段的分布和数目及血管受累部位是决定预后的关键因素.%Objective To analyze infarcts distribution and vascular malformation in patients with multiple infarcts in the posterior circulation and to investigate their correlation with the disease prognosis.Methods Thirty-four patients who had more than one infarct in the posterior circulation as shown on MRI were enrolled in the study.The digital subtraction angiography (DSA) of aortic arch and whole brain were performed on all patients and the images were analyzed and re-evaluated by two senior clinicians respectively.All the patients were assessed using Modified Rankin Scale (MRS) at discharge and correlation of infarcts distribution and vascular malformation with prognosis was evaluated.Results Infarct lesions most often involved pons (22 patients) and the middle (pons and anterior inferior cerebellum) plus distal territories (rostral brainstem, superior cerebellum and occipital and temporal

  17. Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Caterina Oriana Aragona

    2016-01-01

    Full Text Available Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

  18. Vascular emergencies.

    Science.gov (United States)

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  19. Hypoxia inducible factor-2α regulates the development of retinal astrocytic network by maintaining adequate supply of astrocyte progenitors.

    Directory of Open Access Journals (Sweden)

    Li-Juan Duan

    Full Text Available Here we investigate the role of hypoxia inducible factor (HIF-2α in coordinating the development of retinal astrocytic and vascular networks. Three Cre mouse lines were used to disrupt floxed Hif-2α, including Rosa26(CreERT2, Tie2(Cre, and GFAP(Cre. Global Hif-2α disruption by Rosa26(CreERT2 led to reduced astrocytic and vascular development in neonatal retinas, whereas endothelial disruption by Tie2(Cre had no apparent effects. Hif-2α deletion in astrocyte progenitors by GFAP(Cre significantly interfered with the development of astrocytic networks, which failed to reach the retinal periphery and were incapable of supporting vascular development. Perplexingly, the abundance of strongly GFAP(+ mature astrocytes transiently increased at P0 before they began to lag behind the normal controls by P3. Pax2(+ and PDGFRα(+ astrocytic progenitors and immature astrocytes were dramatically diminished at all stages examined. Despite decreased number of astrocyte progenitors, their proliferation index or apoptosis was not altered. The above data can be reconciled by proposing that HIF-2α is required for maintaining the supply of astrocyte progenitors by slowing down their differentiation into non-proliferative mature astrocytes. HIF-2α deficiency in astrocyte progenitors may accelerate their differentiation into astrocytes, a change which greatly interferes with the replenishment of astrocyte progenitors due to insufficient time for proliferation. Rapidly declining progenitor supply may lead to premature cessation of astrocyte development. Given that HIF-2α protein undergoes oxygen dependent degradation, an interesting possibility is that retinal blood vessels may regulate astrocyte differentiation through their oxygen delivery function. While our findings support the consensus that retinal astrocytic template guides vascular development, they also raise the possibility that astrocytic and vascular networks may mutually regulate each other

  20. Vascular dysfunction in patients with young β-thalassemia: relation to cardiovascular complications and subclinical atherosclerosis.

    Science.gov (United States)

    Adly, Amira Abdel Moneam; El-Sherif, Nayera Hazaa; Ismail, Eman Abdel Rahman; El-Zaher, Yosra Abd; Farouk, Amal; El-Refaey, Asmaa Mohamed; Wahba, Mohammed Samy

    2015-11-01

    We aimed to study the endothelial dysfunction among children and adolescents with transfusion-dependent β-thalassemia using von Willebrand factor antigen (VWF:Ag) and flow cytometric analysis of circulating CD144(+) endothelial microparticles (EMPs) and endothelial progenitor cells (CD34(+)VEGFR2(+)) and assess their relation to iron overload, erythropoietin and chelation therapy as well as echocardiographic parameters and carotid intima-media thickness. The VWF:Ag, EMPs, and CD34(+)VEGFR2(+) cells were significantly higher among patients with β-thalassemia than controls (P < .001). The type of chelation and patients' compliance did not influence the results. No significant correlations were found between the studied vascular markers. Patients with evident heart disease had higher VWF: Ag, EMPs, and CD34(+)VEGFR2(+) cells than those without. Carotid intima-media thickness was increased among patients but not correlated with vascular markers. We suggest that procoagulant EMPs and VWF: Ag are involved in cardiovascular complications in patients with young β-thalassemia. CD34(+)VEGFR2(+) cells were further increased in response to tissue injury contributing to reendothelialization and neovascularization.

  1. What Is Vascular Disease?

    Science.gov (United States)

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  2. Diabetes and Vascular Disease

    Science.gov (United States)

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  3. Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

    Science.gov (United States)

    Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

    2013-12-01

    Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as arterial wall calcification and possible applications to regenerative therapies

  4. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

    Directory of Open Access Journals (Sweden)

    Sarah L Appleby

    Full Text Available Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+ population of non-adherent endothelial forming cells (naEFCs which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38 together with mature endothelial cell markers (VEGFR2, CD144 and CD31. These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8 or myeloid markers (CD11b and CD14 which distinguishes them from 'early' endothelial progenitor cells (EPCs. Functional studies demonstrated that these naEFCs (i bound Ulex europaeus lectin, (ii demonstrated acetylated-low density lipoprotein uptake, (iii increased vascular cell adhesion molecule (VCAM-1 surface expression in response to tumor necrosis factor and (iv in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs. Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  5. Effect of Different Doses of Perindopril on Endothelial Progenitor Cells and Vascular Endothelial Function in Patients With Coronary Artery Disease%培哚普利对冠心病患者循环血内皮祖细胞及血管内皮功能的影响

    Institute of Scientific and Technical Information of China (English)

    谈红; 王雪; 李晓燕; 许琳; 苏莉; 胡瑛; 杨燕; 陈英剑; 张国明

    2015-01-01

    目的:探讨不同剂量培哚普利在冠心病治疗中对循环血内皮祖细胞(EPCs)水平及血管内皮功能的影响。  方法:选取我院经冠状动脉造影确诊为冠心病的患者84例,随机分为对照组(n=27,给予常规药物),小剂量组(n=29,给予常规药物+4 mg培哚普利)和大剂量组(n=28,给予常规药物+8 mg培哚普利)。随访12周,治疗前后各组分别采用流式细胞术检测EPCs水平,采用超声测定肱动脉血管舒张功能(FMD),同时检测高敏C反应蛋白(hs-CRP)、血管紧张素II(Ang II)水平。  结果:治疗12周后,对照组、小剂量组及大剂量组患者较治疗前循环血EPCs、肱动脉FMD均有不同程度的增高,hs-CRP水平均有不同程度的降低( P  结论:培哚普利对循环血EPCs有一定的动员作用,可显著改善血管内皮功能,且较大剂量效果更显著。%Objective: To investigate the effect of different doses of perindopril on peripheral endothelial progenitor cells (EPCs) and vascular endothelial function in patients with coronary artery disease (CAD) . Methods: A total of 84 CAD patients with coronary angiography confirmed diagnosis were divided into 3 groups: Control group, the patients received routine medication, n=27. Low-dose group, the patients received routine medication with perindopril for 4mg, n=29. High-dose group, the patients received routine medication with perindopril for 8mg, n=28. All patients were treated for 12 weeks. The EPCs level was detected by flow cytometry assay, flow-mediated-dilation (FMD) function in brachial artery was measured by ultrasound and plasma levels of high sensitivity C-reactive protein (hs-CRP), angiotensin II (AngII) were examined in all groups. Results: ① After12 weeks of treatment, the EPCs level and FMD function had certain improvement, hs-CRP level decreased in various degrees in all 3 groups, P group showed increased EPCs level and

  6. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  7. Embryonic Heart Progenitors and Cardiogenesis

    Science.gov (United States)

    Brade, Thomas; Pane, Luna S.; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl-Ludwig

    2013-01-01

    The mammalian heart is a highly specialized organ, comprised of many different cell types arising from distinct embryonic progenitor populations during cardiogenesis. Three precursor populations have been identified to contribute to different myocytic and nonmyocytic cell lineages of the heart: cardiogenic mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells (CNCCs). This review will focus on molecular cues necessary for proper induction, expansion, and lineage-specific differentiation of these progenitor populations during cardiac development in vivo. Moreover, we will briefly discuss how the knowledge gained on embryonic heart progenitor biology can be used to develop novel therapeutic strategies for the management of congenital heart disease as well as for improvement of cardiac function in ischemic heart disease. PMID:24086063

  8. Defining the potential for cell therapy for vascular disease using animal models

    OpenAIRE

    Gulati, Rajiv; Simari, Robert D.

    2009-01-01

    Cell-based therapeutics are currently being developed for a wide array of unmet medical needs. As obstructive vascular disease is the major cause of mortality in the world, cell-based strategies aimed at developing novel therapies or improving current therapies are currently under study. These studies are based on the evolving understanding of the biology of vascular progenitor cells, which has in turn led to the availability of well-defined sources of vascular cells for delivery. Crucial to ...

  9. 脱氢野百合碱诱发肺动脉高压犬的循环内皮祖细胞数量和功能变化%Quantitative and functional changes of circulating endothelial progenitor cells in dogs with dehydromonocrotaline-induced pulmonary artery hypertension

    Institute of Scientific and Technical Information of China (English)

    曾春来; 夏良; 马彩艳; 刘善宽; 胡晓晟; 王兴祥; 陈君柱

    2008-01-01

    目的 观察脱氢野百合碱(DHMC)诱发犬肺动脉高压形成前后循环内皮祖细胞数量和功能的变化.方法 10只Beagle犬经右心室注射DHMC诱导肺动脉高压(PAH).注射DHMC前、注射后6周采集静脉血,用流式细胞仪分析AC133和KDR检测双阳性的细胞数量.收集单个核细胞体外培养7 d后进行乙酰化低密度脂蛋白胆固醇(DiLDL)摄取和凝集素-Ⅰ(UEA-Ⅰ)结合反应,并进行体外血管生成试验.计量资料采用(-x)±s表示,采用配对t检验进行统计学分析.结果 10只Beagle犬注射DHMC后9只存活,1只于第2天死亡.注射DHMC后6周肺动脉平均压由(11.3±2.0)mm Hg(1 mm Hg=0.133 kPa)增高到(20.2±1.6)mm Hg(t=10.307,P<0.01).PAH形成前后经流式细胞仪分析的ACl33和KDR双阳性细胞数量分别为(632.8±42.8)个/nil和(206.1±26.8)个/m1(t=25.361,P<0.01);体外培养7 d的细胞中UEA-Ⅰ和DiLDL染色双阳性细胞数量分别为(41±6)个/200倍视野和(22±6)个/200倍视野(t=6.510,P<0.01).体外成血管试验中形成的血管数为(21.1±2.8)支/200倍视野和(11.2±2.8)y./200倍视野(t=7.583,P<0.01).结论 犬肺动脉高压形成后循环内皮祖细胞数最减少,成血管能力下降.%Objective To determine the quantitive and functional changes of circulating endothelial progenitor cells(EPCs)in dogs with dehydromonocrotaline-induced pulmonary artery hypertension(PAH).Metllods Dehydromonocrotaline was injected into the canine right ventricle to induce pulmonary hypertension.Circulating EPCs were enumerated as AC133+,KDR+ cells by fluorescence-activated celi sorter using counting beads,and the number and activity of EPCs after in vitro expansion were determined by acLDL uptake/lectin staining assay and in vitro tubale forming assay.Results Nine of the 10 beagles survived after dehydromonocmtaline iniectiom Six weeks later,mean pulmonary artery pressure increased from(11.3±2.0)mm Hg(1 mm Hg=0.133 kPa) to (20.2±1.6)mm Hg(t=10.307,P<0.01),and

  10. The Pulmonary Circulation and Exercise Responses in the Elderly

    OpenAIRE

    Taylor, Bryan J.; Johnson, Bruce D.

    2010-01-01

    Aging is associated with a progressive deterioration in the structure and function of the pulmonary circulation. Remodeling of the pulmonary vasculature occurs from maturity to senescence that is characterized by an increase in pulmonary vascular stiffness, pulmonary vascular pressures, and pulmonary vascular resistance along with increased heterogeneity of alveolar ventilation and pulmonary perfusion and decreased pulmonary capillary blood volume and membrane diffusing capacity that is consi...

  11. Proatherogenic pathways leading to vascular calcification

    Energy Technology Data Exchange (ETDEWEB)

    Mazzini, Michael J. [Department of Cardiology, Boston University Medical Center, Boston, MA (United States); Schulze, P. Christian [Department of Medicine, Boston University Medical Center, Boston, MA (United States)]. E-mail: christian.schulze@bmc.org

    2006-03-15

    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease.

  12. Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice

    OpenAIRE

    Segal, Mark S.; Sautina, Laura; Li, Shiyu; Diao, YanPeng; Agoulnik, Alexander I.; Kielczewski, Jennifer; McGuane, Jonathan T.; Grant, Maria B.; Conrad, Kirk P.

    2012-01-01

    The ovarian peptide hormone, relaxin, circulates during pregnancy, contributing to profound maternal vasodilation through endothelial and nitric oxide (NO)–dependent mechanisms. Circulating numbers of bone marrow–derived endothelial cells (BMDECs), which facilitate angiogenesis and contribute to repair of vascular endothelium, increase during pregnancy. Thus, we hypothesized that relaxin enhances BMDEC NO production, circulating numbers, and function. Recombinant human relaxin-2 (rhRLX) stimu...

  13. Engineered human vascularized constructs accelerate diabetic wound healing.

    Science.gov (United States)

    Shen, Yu-I; Cho, Hongkwan; Papa, Arianne E; Burke, Jacqueline A; Chan, Xin Yi; Duh, Elia J; Gerecht, Sharon

    2016-09-01

    Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeutic modality for diabetic wound healing. We developed a wound model in immunodeficient rodent and treated it with engineered vascularized constructs from endothelial progenitors or early vascular cells-derived from human induced pluripotent stem cells (hiPSCs) reprogrammed either from healthy donor or type-1 diabetic patient. We found that all vascularized constructs expedited wound closure and reperfusion, with endothelial progenitor constructs having the earliest maximum closure rate followed closely by healthy and diabetic hiPSC-derivative constructs. This was accompanied by rapid granulation layer formation and regression in all vascularized construct groups. Macrophage infiltration into the hydrogel matrix occurred during early stages of healing, seeming to facilitate rapid neovascularization of the wound that could then better persist in the vascularized constructs. Blood perfusion of the human vasculature could be detected after three days, indicating rapid integration with the host vasculature. Overall, we propose a potential therapeutic strategy using allograft or autologous vascularized constructs to treat type-1 diabetic wounds. This approach highlights the unprecedented prospects of designing patient-specific stem cell therapy. PMID:27328431

  14. Retina vascular network recognition

    Science.gov (United States)

    Tascini, Guido; Passerini, Giorgio; Puliti, Paolo; Zingaretti, Primo

    1993-09-01

    The analysis of morphological and structural modifications of the retina vascular network is an interesting investigation method in the study of diabetes and hypertension. Normally this analysis is carried out by qualitative evaluations, according to standardized criteria, though medical research attaches great importance to quantitative analysis of vessel color, shape and dimensions. The paper describes a system which automatically segments and recognizes the ocular fundus circulation and micro circulation network, and extracts a set of features related to morphometric aspects of vessels. For this class of images the classical segmentation methods seem weak. We propose a computer vision system in which segmentation and recognition phases are strictly connected. The system is hierarchically organized in four modules. Firstly the Image Enhancement Module (IEM) operates a set of custom image enhancements to remove blur and to prepare data for subsequent segmentation and recognition processes. Secondly the Papilla Border Analysis Module (PBAM) automatically recognizes number, position and local diameter of blood vessels departing from optical papilla. Then the Vessel Tracking Module (VTM) analyses vessels comparing the results of body and edge tracking and detects branches and crossings. Finally the Feature Extraction Module evaluates PBAM and VTM output data and extracts some numerical indexes. Used algorithms appear to be robust and have been successfully tested on various ocular fundus images.

  15. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul;

    2010-01-01

    with tumor necrosis factor-alpha (TNF alpha) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n = 32, and psoriatic arthritis, n = 17) initiating TNF alpha inhibitor therapy (infliximab, n = 38......The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......Euro parts per thousand 0.001), whereas total aggrecan was lower (662 mu g/l (223-2,219) vs. 816 (399-2,190),p a parts per thousand currency signaEuro parts per thousand 0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p a parts per thousand currency signa...

  16. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Hetland, Merete Lund; Sørensen, Inge Juul;

    2010-01-01

    with tumor necrosis factor-alpha (TNFα) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNFα inhibitor therapy (infliximab, n=38; etanercept, n=8......The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......-2,190), p≤0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p≤0.03) in clinical responders (n=24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p≤0.02) in non-responders (n=13). The study demonstrated...

  17. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Ostergaard, Mikkel; Nielsen, Hans Jørgen;

    2010-01-01

    with tumor necrosis factor-alpha (TNFa) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNFa inhibitor therapy (infliximab, n=38; etanercept, n=8......The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......-2,190), p=0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p=0.03) in clinical responders (n=24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p=0.02) in non-responders (n=13). The study demonstrated...

  18. Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Brenner Benjamin

    2009-10-01

    Full Text Available Abstract Background The function of endothelial progenitor cells (EPCs, which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD, the enzyme that neutralizes superoxide anion (O2-. Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. Methods The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. Results EPCs from diabetic patients generated more O2-, had higher NAD(PH oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Conclusion Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

  19. Society for Vascular Medicine

    Science.gov (United States)

    ... 2017 Learn more Patient Information Pages from Vascular Medicine August 2016 The Vascular Laboratory More info for ... Learn more. Trending Now: Hot Topics in Vascular Medicine Video Series Fibromuscular Dysplasia (FMD) with Drs. Jeffrey ...

  20. High dose ionizing irradiation induces an early and transient increase in peripheral blood hematopoietic progenitor cells; L`exposition aigue aux radiations ionisantes induit un recrutement transitoire des progeniteurs hematopoietiques au niveau du sang peripherique: implications therapeutiques potentielles

    Energy Technology Data Exchange (ETDEWEB)

    Drouet, M.; Mathieu, J.; Grenier, N.; Vetillard, J.; Chauvelot, F.; Thierry, D.; Mestries, J.C.; Herodin, F. [Centre de Recherches du Service de Sante des Armees, La Tronche, 38 - Grenoble (France)]|[Centre de Recherches du Service de Sante des Armees - Centre d`Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)

    1997-12-31

    Nonhuman primates exposed to ionizing radiation exhibit an early and transient increase in peripheral blood committed hematopoietic progenitor cells. The management of bone marrow aplasia secondary to accidental irradiation could be based in part on the re-infusion of those circulating autologous progenitors following a period of ex vivo expansion with cytokines. (authors)

  1. Treatment of transfection hypoxia inducible factor gene into endothelial progenitor cells for vascular regeneration in rat ischemic hind-limb%缺氧诱导因子转染内皮祖细胞治疗大鼠缺血后肢

    Institute of Scientific and Technical Information of China (English)

    王三明; 王花; 彭林; 王深明

    2010-01-01

    Objective To explore whether the overexpression of hypoxia inducible factor (HIF)transfection into endothelial progenitor cells (EPCs) is beneficial on eovascularization of rat ischemic hindlimb and limb survival.Methods SD rat ischemic hind-limb models were established,and randomly divided into three groups,six rats each group.Lipofectamine 2000 mediated Eukaryotic expression vector of HIF was transfected into EPCs from marrow,which then was injected into rats via vena caudalis.Observe how EPCs transfected with HIF gene gathered at the ischemic part and facilitated angiogenesis.Results ( 1 ) General limb disability: limb restoration rate of Group EPC,EPC + HIF were obviously higher than that of Group PBS (P <0.05).(2) Micro vessel density (MVD): compared with Group PBS,there was a marked increase of MVD in Group EPC,HIF at each time point (P < 0.05 ).14 and 21 days after operation,MVD in Group HIF was higher than that in Group EPC (P <0.05).(3) HIF and Vascular endothelial growth factor (VEGF) Expression in ischemic limbs:compared with Group PBS,EPC,Expression of HIF and VEGF protein in Group HIF was significantly increased (P < 0.05).There was obvious increase in expression of HIF and VEGF protein in Group EPC compared with Group PBS ( P < 0.05 ).(4) Blood perfusion:seven days after operation,rat limb perfusion in all groups was reduced; 14,21 days after operation,compared with PBS controlled group,there was notable blood perfusion recovery in Group EPC and HIF ( P < 0.01 ).Blood perfusion of Group EPC was less than that of Group HIF ( P < 0.05 ).Conclusion EPCs transfected with HIF gene had a significant impact on angiogenesis in ischemic.Combined application of HIF gene enhanced the effect of EPCs treatment of augment naturally impaired neovascularization in animal model of experimentally induced limb ischemia.%目的 使用缺氧诱导因子-1α(HIF-1α)转染内皮祖细胞(EPC)治疗大鼠后肢缺血,观察EPC、HIF-1α转染EPC对大鼠缺

  2. The poster as modernist progenitor

    Directory of Open Access Journals (Sweden)

    Katherine Hauser

    2015-12-01

    Full Text Available Ruth E. Iskin’s The Poster: Art, Advertising. Design, and Collecting, 1860s-1900s positions the late-nineteenth-century advertising poster as the progenitor of valued modernist practices typically attached solely to photography and film. Modernist biases separating high art from mass culture account for scholars ignoring posters, however the poster ushered in an innovative reductive graphic style as well as pioneered the notion of multiple originals.

  3. Endothelial Progenitor Cells in Sprouting Angiogenesis: Proteases Pave the Way.

    Science.gov (United States)

    Laurenzana, A; Fibbi, G; Margheri, F; Biagioni, A; Luciani, C; Del Rosso, M; Chillà, A

    2015-01-01

    Sprouting angiogenesis consists of the expansion and remodelling of existing vessels, where the vascular sprouts connect each other to form new vascular loops. Endothelial Progenitor Cells (EPCs) are a subtype of stem cells, with high proliferative potential, able to differentiate into mature Endothelial Cells (ECs) during the neovascularization process. In addition to this direct structural role EPCs improve neovascularization, also secreting numerous pro-angiogenic factors able to enhance the proliferation, survival and function of mature ECs, and other surrounding progenitor cells. While sprouting angiogenesis by mature ECs involves resident ECs, the vasculogenic contribution of EPCs is a high hurdle race. Bone marrowmobilized EPCs have to detach from the stem cell niche, intravasate into bone marrow vessels, reach the hypoxic area or tumour site, extravasate and incorporate into the new vessel lumen, thus complementing the resident mature ECs in sprouting angiogenesis. The goal of this review is to highlight the role of the main protease systems able to control each of these steps. The pivotal protease systems here described, involved in vascular patterning in sprouting angiogenesis, are the matrix-metalloproteinases (MMPs), the serineproteinases urokinase-type plasminogen activator (uPA) associated with its receptor (uPAR) and receptorassociated plasminogen/plasmin, the neutrophil elastase and the cathepsins. Since angiogenesis plays a critical role not only in physiological but also in pathological processes, such as in tumours, controlling the contribution of EPCs to the angiogenic process, through the regulation of the protease systems involved, could yield new opportunities for the therapeutic prospect of efficient control of pathological angiogenesis. PMID:26321757

  4. Vascular endothelial growth factor and remedial angiogenesis%血管内皮生长因子与治疗性血管生成研究进展

    Institute of Scientific and Technical Information of China (English)

    郭敬; 王烈

    2008-01-01

    血管内皮生长因子(vascular endothelial growtll factor,VEGF)是内皮细胞特异的有丝分裂原,有促进内皮细胞增生、增强血管通透性、加速新血管形成的作用.血管生成是一个具有重要生理、病理意义的过程.在人体的创伤愈合、炎症反应、器官再生过程以及肿瘤生长转移、血管增生性疾病中,血管生成有重要作用.治疗性血管生成是指利用成血管诱导因子或内皮祖细胞,模拟体内血管生成机制,促进新生血管形成,改善侧支循环.本文就VEGF和治疗性血管生成研究进展做一综述.%Vascular endothelial growth factor (VEGF) is the endothelial cell-specific mitogen, facili-tates endothelial cell proliferation, increases vascular permeability and accelerates the formation of new blood vessels role. Angiogenesis is an important physiological and pathological significance of the process. In the human wound healing, inflammation, organ regeneration and tumor growth and metastasis, vascular prolifer-ative diseases, angiogenesis is an important role. Therapeutic angiogenesis is the use of inducible factor or vascular endothelial progenitor ceils, simulates in vivo angiogenesis mechanism, promotes angiogenesis and improves the collateral circulation. In this paper, VEGF and therapeutic ansiogenesis research progress were reviewed.

  5. Circulating endothelial cells participate in the in vivo endothelialization of vascular prosthesis: An animal experiment%循环内皮细胞参与人工血管体内内皮化过程的动物实验

    Institute of Scientific and Technical Information of China (English)

    王毅; 陈易人; 戴坤扬; 钮宏文; 伍波; 李里; 戚大川

    2007-01-01

    ,差异有显著性意义(P<0.05).结论:骨髓内皮细胞衬里的ePTFE人工血管在体内能较快完成内皮化过程,能抑制内膜增生;循环内皮细胞作为内皮细胞的潜在来源,具有一定临床应用价值.%BACKGROUND: Experiments have demonstrated that autologous vascular endothelial cells if transplanted onto artificial vascular cavosurface, can enhance the patency rate of vasotransplantation. Whether seeding of prostheses interposition grafts with bone marrow-derived endothelial cells is effective for in vivo endothelialization of artificial vessels remains unclear.OBJECTIVE: To observe the effect of endothelialization of vascular prosthesis by seeding prostheses interposition grafts with bone marrow-derived endothelial cells in animals.DESIGN: A controlled animal experimental study.SETTING: Shanghai Sixth People's Hospital.MATERIALS: This study was carried out in the Shanghai Sixth People's Hospital between September 2000 and October 2001. Twenty hybrid dogs from Shanghai, of either gender, aged 1.0 to 2.0 years old, weighing (18.7±2.3) kg, were involved in this study.METHODS: Bone marrow-derived mononuclear cells were isolated from the dogs. The endothelialization of ePTFE prostheses interposition grafts (4 mm×4 cm and 8 mm×5 cm)was carried out. Common carotid artery transplantation:Ten laboratory dogs were involved. Common carotid artery of 4 cm was resected from each dog. ePTFE prostheses interposition grafts of 4 mm×4 cm was transplanted into the bilateral common carotid artery, and prostheses interposition grafts were performed endothelialization, namely experimental group. Those prostheses interposition grafts, which were not performed endothelialization, were named as control group. Five dogs were used in each group. Patency rate and blood flow rate of transplanted vessels were detected with a color ultrasonograph 2 weeks and 2 months after operation.Inferior caval vein transplantation: Six of the rest 10 dogs were used for experiments. Under the

  6. Hydrogel Surfaces to Promote Attachment and Spreading of Endothelial Progenitor Cells

    OpenAIRE

    Camci-Unal, Gulden; Nichol, Jason William; Bae, Hojae; Tekin, Halil; Bischoff, Joyce; Khademhosseini, Ali

    2012-01-01

    Endothelialization of artificial vascular grafts is a challenging process in cardiovascular tissue engineering. Functionalized biomaterials could be promising candidates to promote endothelialization in repair of cardiovascular injuries. The purpose of this study was to synthesize hyaluronic acid (HA) and heparin based hydrogels that could promote adhesion and spreading of endothelial progenitor cells (EPCs). We report that the addition of heparin into HA-based hydrogels provides an attractiv...

  7. Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.

    Directory of Open Access Journals (Sweden)

    Stephanie Hum

    Full Text Available The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific mouse was crossed with a diphtheria toxin mouse (DTA to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma.

  8. Hypoxia, vascular smooth muscles and endothelium

    Directory of Open Access Journals (Sweden)

    Calvin K. Chan

    2013-02-01

    Full Text Available Hypoxia, or the lack of oxygen, has multiple impacts on the vascular system. The major molecular sensors for hypoxia at the cellular level are hypoxia inducible factor and heme oxygenase. Hypoxia also acts on the vasculature directly conveying its damaging effects through disruption of the control of vascular tone, particularly in the coronary circulation, enhancement of inflammatory responses and activation of coagulation pathways. These effects could be particularly detrimental under pathological conditions such as obstructive sleep apnea and other breathing disorders.

  9. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues.

    Science.gov (United States)

    Shan, Tizhong; Liu, Weiyi; Kuang, Shihuan

    2013-01-01

    Adipose tissues regulate metabolism, reproduction, and life span. The development and growth of adipose tissue are due to increases of both adipocyte cell size and cell number; the latter is mediated by adipocyte progenitors. Various markers have been used to identify either adipocyte progenitors or mature adipocytes. The fatty acid binding protein 4 (FABP4), commonly known as adipocyte protein 2 (aP2), has been extensively used as a marker for differentiated adipocytes. However, whether aP2 is expressed in adipogenic progenitors is controversial. Using Cre/LoxP-based cell lineage tracing in mice, we have identified a population of aP2-expressing progenitors in the stromal vascular fraction (SVF) of both white and brown adipose tissues. The aP2-lineage progenitors reside in the adipose stem cell niche and express adipocyte progenitor markers, including CD34, Sca1, Dlk1, and PDGFRα. When isolated and grown in culture, the aP2-expressing SVF cells proliferate and differentiate into adipocytes upon induction. Conversely, ablation of the aP2 lineage greatly reduces the adipogenic potential of SVF cells. When grafted into wild-type mice, the aP2-lineage progenitors give rise to adipose depots in recipient mice. Therefore, the expression of aP2 is not limited to mature adipocytes, but also marks a pool of undifferentiated progenitors associated with the vasculature of adipose tissues. Our finding adds to the repertoire of adipose progenitor markers and points to a new regulator of adipose plasticity.

  10. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

    Science.gov (United States)

    Gargett, C E; Schwab, K E; Brosens, J J; Puttemans, P; Benagiano, G; Brosens, I

    2014-07-01

    The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition. PMID:24674992

  11. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice

    OpenAIRE

    Marrotte, Eric J.; Chen, Dan-Dan; Hakim, Jeffrey S.; Chen, Alex F.

    2010-01-01

    Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating...

  12. Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells

    OpenAIRE

    Nguyen Huu, Sau; Oster, Michèle; Uzan, Serge; Chareyre, Fabrice; Aractingi, Sélim; Khosrotehrani, Kiarash

    2007-01-01

    Fetal progenitor cells enter the maternal circulation during pregnancy and can persist for decades. We aimed to determine the role of these cells in tissue inflammation during pregnancy. WT female mice were mated to males transgenic for the EGFP (ubiquitous) or the luciferase gene controlled by the VEGF receptor 2 (VEGFR2; V-Luc) promoter. A contact hypersensitivity reaction was triggered during such pregnancies. Fetal cells were tracked by using real-time quantitative amplification of the tr...

  13. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Peter E Westerweel

    Full Text Available BACKGROUND: Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. METHODS: Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. RESULTS: In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. CONCLUSION: EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  14. Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

    Science.gov (United States)

    Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

    2013-01-01

    Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

  15. Branding of vascular surgery.

    Science.gov (United States)

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  16. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant

    OpenAIRE

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-01-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cel...

  17. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts

    Science.gov (United States)

    Liu, Yu; Chen, Li; Diaz, Andrea Diaz; Benham, Ashley; Xu, Xueping; Wijaya, Cori S.; Fa’ak, Faisal; Luo, Weijia; Soibam, Benjamin; Azares, Alon; Yu, Wei; Lyu, Qiongying; Stewart, M. David; Gunaratne, Preethi; Cooney, Austin; McConnell, Bradley K.; Schwartz, Robert J.

    2016-01-01

    Mesp1 directs multipotential cardiovascular cell fates, even though it’s transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1’s transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1Cre/+; Rosa26EYFP/+ ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells. PMID:27538477

  18. Fasudil inhibits the myogenic response in the fetal pulmonary circulation

    OpenAIRE

    Tourneux, Pierre; Chester, Marc; Grover, Theresa; Abman, Steven H.

    2008-01-01

    In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent v...

  19. Collagen vascular disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this page, ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many of many ...

  20. Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model

    Science.gov (United States)

    Lopez-Vilchez, I; Diaz-Ricart, M; Navarro, V; Torramade, S; Zamorano-Leon, J; Lopez-Farre, A; Galan, A M; Gasto, C; Escolar, G

    2016-01-01

    There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (Pcultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (Pcultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks. PMID:27598970

  1. Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.

    Science.gov (United States)

    Lopez-Vilchez, I; Diaz-Ricart, M; Navarro, V; Torramade, S; Zamorano-Leon, J; Lopez-Farre, A; Galan, A M; Gasto, C; Escolar, G

    2016-01-01

    There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (Ptreatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (Ptreatment for 24 weeks. PMID:27598970

  2. Changes in the Number and Functional Activity of Circulating Endothelial Progenitor Cells in Patients with Ischemic Heart Disease%缺血性心脏病患者外周血中内皮祖细胞数量和功能的变化

    Institute of Scientific and Technical Information of China (English)

    陈海波; 张淑霞

    2007-01-01

    目的:观察缺血性心脏病(ischemic heart disease, IHD)患者外周血中内皮祖细胞(endothelial progenitor cells, EPCs)数量及功能的变化.方法:IHD患者和对照者各23例,用密度梯度离心法从外周血中分离单个核细胞,用流式细胞仪测量外周血中CD+细胞以鉴定EPCs.分别观察EPCs的粘附能力、迁移能力和体外生成血管能力.结果:IHD患者外周血中EPCs数量明显低于对照组,其粘附能力、迁移能力和体外生成血管能力也明显受损.结论:IHD患者外周血中EPCs数量降低且功能减退.

  3. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt;

    2000-01-01

    was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...... patients (P analysis showed that vascular grading contributed with independent prognostic value in all patients (P

  4. Remodelling the vascular microenvironment of glioblastoma with alpha-particles

    Science.gov (United States)

    Behling, Katja; Maguire, William F.; Di Gialleonardo, Valentina; Heeb, Lukas E.M.; Hassan, Iman F.; Veach, Darren R.; Keshari, Kayvan R.; Gutin, Philip H.; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    Rationale Tumors escape anti-angiogenic therapy by activation of pro-angiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We investigated targeted α-particle therapy with 225Ac-E4G10 as an anti-vascular approach and previously showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here we investigate changes in tumor-vascular morphology and functionality caused by 225Ac-E4G10. Methods We investigated remodeling of tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4 kBq dose of 225Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphological changes in the tumor blood brain barrier microenvironment. Multi-color flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted magnetic resonance imaged functional changes of the tumor vascular network. Results The mechanism of drug action is a combination of glioblastoma vascular microenvironment remodeling, edema relief, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis was lessened and resulted in increased perfusion and reduced diffusion. Pharmacological uptake of dasatinib into tumor was enhanced following α-particle therapy. Conclusion Targeted anti-vascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of Platelet-derived growth factor driven glioblastoma. PMID:27261519

  5. The progenitors of stripped-envelope supernovae

    Science.gov (United States)

    Elias-Rosa, N.

    2013-05-01

    The type Ib/c SNe are those explosions which come from massive star populations, but lack hydrogen and helium. These have been proposed to originate in the explosions of massive Wolf-Rayet stars, and we should easily be able to detect the very luminous, young progenitors if they exist. However, there has not been any detection of progenitors so far. I present the study of two extinguished Type Ic SNe 2003jg and 2004cc. In both cases there is no clear evidence of a direct detection of their progenitors in deep pre-explosion images. Upper limits derived by inserting artificial stars of known brightness at random positions around the progenitor positions (M_v>-8.8 and M_v>-9 magnitudes for the progenitors of SN 2003jg and SN 2004cc, respectively) are brighter than those expected for a massive WC (Wolf-Rayet, carbon-rich) or WO (Wolf-Rayet, oxygen-rich) (e.g., approximately between -3 and -6 in the LMC). Therefore, this is perhaps further evidence that the most massive stars may give rise to black-holes forming SNe, or it is an undetected, compact massive star hidden by a thick dust lane. However the extinction toward these SNe is currently one of the largest known. Even if these results do not directly reveal the nature of the type Ic SN progenitors, they can help to characterize the dusty environment which surrounded the progenitor of the stripped-envelope CC-SNe.

  6. Progenitor Cells and Podocyte Regeneration

    OpenAIRE

    Shankland, Stuart J.; Pippin, Jeffrey W.; Duffield, Jeremy S.

    2014-01-01

    The very limited ability of adult podocytes to proliferate in vivo is clinically significant because: podocytes form a vascular barrier which is functionally critical to the nephron; podocyte hypoplasia is a characteristic of disease; and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density is almost c...

  7. How to Prevent Vascular Disease

    Science.gov (United States)

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  8. Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

    Directory of Open Access Journals (Sweden)

    Qishan Chen

    2013-01-01

    Full Text Available Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs, and vascular smooth muscle cells (VSMCs and its interaction with extracellular matrix (ECM play a critical role in the processes. Matrix metalloproteinases (MMPs, well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential.

  9. Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver metastasis vascularity and volume

    OpenAIRE

    Davies, M M; Jonas, S. K.; Kaur, S.; Allen-Mersh, T G

    2000-01-01

    The extent to which plasma levels of angiogenic factors in healthy individuals and tumour volume-related variations in colorectal cancer affect the accuracy of circulating angiogenic factors as predictors of colorectal cancer vascularity is unknown. We used enzyme-linked immunosorbant assay to measure plasma vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels in colorectal liver metastasis (CLM) patients, and ‘no cancer’ controls. CLM volume was determin...

  10. Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor.

    Science.gov (United States)

    Peng, Tien; Tian, Ying; Boogerd, Cornelis J; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Evans, Sylvia M; Morrisey, Edward E

    2013-08-29

    Co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung. Here we show that the murine pulmonary vasculature develops even in the absence of lung development. We have identified a population of multipotent cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2, Gli1 and Isl1. We show that CPPs arise from cardiac progenitors before lung development. Lineage tracing and clonal analysis demonstrates that CPPs generate the mesoderm lineages within the cardiac inflow tract and lung including cardiomyocytes, pulmonary vascular and airway smooth muscle, proximal vascular endothelium, and pericyte-like cells. CPPs are regulated by hedgehog expression from the foregut endoderm, which is required for connection of the pulmonary vasculature to the heart. Together, these studies identify a novel population of multipotent cardiopulmonary progenitors that coordinates heart and lung co-development that is required for adaptation to terrestrial existence.

  11. Severe Type 2 Diabetes Induces Reversible Modifications of Endothelial Progenitor Cells Which are Ameliorate by Glycemic Control

    Science.gov (United States)

    De Pascale, Maria Rosaria; Bruzzese, Giuseppe; Crimi, Ettore; Grimaldi, Vincenzo; Liguori, Antonio; Brongo, Sergio; Barbieri, Michelangela; Picascia, Antonietta; Schiano, Concetta; Sommese, Linda; Ferrara, Nicola; Paolisso, Giuseppe; Napoli, Claudio

    2016-01-01

    Background Circulating endothelial progenitors cells (EPCs) play a critical role in neovascularization and endothelial repair. There is a growing evidence that hyperglycemia related to Diabetes Mellitus (DM) decreases EPC number and function so promoting vascular complications. Aim of the Study This study investigated whether an intensive glycemic control regimen in Type 2 DM can increase the number of EPCs and restores their function. Methods Sixty-two patients with Type 2 DM were studied. Patients were tested at baseline and after 3 months of an intensive regimen of glycemic control. The Type 2 DM group was compared to control group of subjects without diabetes. Patients with Type 2 DM (mean age 58.2±5.4 years, 25.6% women, disease duration of 15.4±6.3 years) had a baseline HgA1c of 8.7±0.5% and lower EPC levels (CD34+/KDR+) in comparison to healthy controls (p<0.01). Results The intensive glycemic control regimen (HgA1c decreased to 6.2±0.3%) was coupled with a significant increase of EPC levels (mean of 18%, p<0.04 vs. baseline) and number of EPCs CFUs (p<0.05 vs. baseline). Conclusion This study confirms that number and bioactivity of EPCs are reduced in patients with Type 2 DM and, most importantly, that the intensive glycemic control in Type 2 DM promotes EPC improvement both in their number and in bioactivity. PMID:27426095

  12. Multifocal vascular lesions.

    Science.gov (United States)

    Levin, Laura E; Lauren, Christine T

    2016-03-01

    Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations. PMID:27607324

  13. Method to study vascular changes in lung exposed to radiation

    International Nuclear Information System (INIS)

    Carbon-11 labeled carbon monoxide is used to measure changes in circulating hemoglobin volume in primary carcinoma within lung and in normal lung resulting from radiation treatment. This 11CO method is being extended to the quantitative measurement of circulating hemoglobin blood volumes in a variety of tumors in humans in an attempt to measure tumor response to chemical therapy; namely, the accessibility of the chemical to the tumor provided by an adequate vascular system

  14. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  15. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient

    Institute of Scientific and Technical Information of China (English)

    Andrew; Hsu; Jen-Fu; Lee; Daniel; E; Cramer; Menq-Jer; Lee

    2011-01-01

    Most hematopoietic stem progenitor cells (HSPCs) reside in bone marrow (BM), but a small amount of HSPCs have been found to circulate between BM and tissues through blood and lymph. Several lines of evidence suggest that sphingosine-1-phosphate (S1P) gradient triggers HSPC egression to blood circulation after mobilization from BM stem cell niches. Stem cells also visit certain tissues. After a temporary 36 h short stay in local tissues, HSPCs go to lymph in response to S1P gradient between lymph and tissue and eventually enter the blood circulation. S1P also has a role in the guidance of the primitive HSPCs homing to BM in vivo, as S1P analogue FTY720 treatment can improve HSPC BM homing and engraftment. In stress conditions, various stem cells or progenitor cells can be attracted to local injured tissues and participate in local tissue cell differentiation and tissue rebuilding through modulation the expression level of S1P1, S1P2 or S1P3 receptors. Hence, S1P is important for stem cells circulation in blood system to accomplish its role in body surveillance and injury recovery.

  16. Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K; Wachtell, K;

    2005-01-01

    Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy...

  17. Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model

    NARCIS (Netherlands)

    K. Larsen (Katarína); K.L. Cheng (Caroline); D. Tempel (Dennie); S. Parker (Sherry); S. Yazdani (Saami); W.K. den Dekker (Wijnand); H.J. Houtgraaf (Jaco); R. de Jong (Renate); S. Swager-ten Hoor (Stijn); E. Ligtenberg (Erik); S.R. Hanson (Stephen); R. Rowland (Steve); F. Kolodgie (Frank); P.W.J.C. Serruys (Patrick); R. Virmani (Renu); H.J. Duckers (Henricus)

    2012-01-01

    textabstractThe Genous™ Bio-engineered R™ stent (GS) aims to promote vascular healing by capture of circulatory endothelial progenitor cells (EPCs) to the surface of the stent struts, resulting in accelerated re-endothelialization. Here, we assessed the function of the GS in comparison to bare-metal

  18. Proteomic and meatbolomic analysis of smooth muscle cells derived from the arterial media and adventitial progenitors of apolipoprotein E-deficient mice

    NARCIS (Netherlands)

    Mayr, M; Zampetaki, A.; Sidibe, A.; Mayr, U.; Yin, X.; Souza, A.I. de; Chung, Y.L.; Madhu, B.; Quax, P.H.; Hu, Y.; Griffiths, J.R.; Xu, Q.

    2008-01-01

    We have recently demonstrated that stem cell antigen 1-positive (Sca-1(+)) progenitors exist in the vascular adventitia of apolipoprotein E-deficient (apoE(-/-)) mice and contribute to smooth muscle cell (SMC) accumulation in vein graft atherosclerosis. Using a combined proteomic and metabolomic app

  19. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari

    2014-01-01

    Full Text Available The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS’s role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

  20. A Multipotent Progenitor Domain Guides Pancreatic Organogenesis

    OpenAIRE

    Zhou, Qiao; Law, Anica Chi-Ying; Rajagopal, Jayaraj; Anderson, William J.; Gray, Paul A.; Douglas A Melton

    2007-01-01

    The mammalian pancreas is constructed during embryogenesis by multipotent progenitors, the identity and function of which remain poorly understood. We performed genome-wide transcription factor expression analysis of the developing pancreas to identify gene expression domains that may represent distinct progenitor cell populations. Five discrete domains were discovered. Genetic lineage-tracing experiments demonstrate that one specific domain, located at the tip of the branching pancreatic tre...

  1. Reactive Oxygen Species in Vascular Formation and Development

    Directory of Open Access Journals (Sweden)

    Yijiang Zhou

    2013-01-01

    Full Text Available Reactive oxygen species (ROS are derived from the metabolism of oxygen and are traditionally viewed as toxic byproducts that cause damage to biomolecules. It is now becoming widely acknowledged that ROS are key modulators in a variety of biological processes and pathological states. ROS mediate key signaling transduction pathways by reversible oxidation of certain signaling components and are involved in the signaling of growth factors, G-protein-coupled receptors, Notch, and Wnt and its downstream cascades including MAPK, JAK-STAT, NF-κB, and PI3K/AKT. Vascular formation and development is one of the most important events during embryogenesis and is vital for postnasal tissue repair. In this paper, we will discuss how ROS regulate different steps in vascular development, including smooth muscle cell differentiation, angiogenesis, endothelial progenitor cells recruitment, and vascular cell migration.

  2. Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.

    Directory of Open Access Journals (Sweden)

    Shyh-Jong Wu

    Full Text Available Vascular remodelling is a critical vasculopathy found in atheromatous diseases and allograft failures. The local renin angiotensin system (RAS has been implicated in vascular remodelling. However, the mechanisms by which the augmented local RAS is associated with the initial event of endothelial cell apoptosis in injured vasculature remain undefined. We induced the apoptosis of human umbilical vein endothelial cells (HUVECs and vascular smooth muscle cells (VSMCs through serum starvation (SS. After the cells were subjected to SS, we found that the mRNA expression of angiotensinogen (AGT was increased by >3-fold in HUVECs and by approximately 2.5-fold in VSMCs. In addition, the expression of angiotensin-converting enzyme (ACE mRNA was increased in VSMCs but decreased to 50% in HUVECs during the same apoptotic process. Increases in the expression of AGT protein and angiotensin II (Ang II were found in a serum-free medium conditioned by HUVECs (SSC. The increased Ang II was suppressed using lisinopril (an ACE inhibitor treatment. Moreover, the activation of ERK1/2 induced by the SSC in VSMCs was also suppressed by losartan. In conclusion, we first demonstrated that the augmented AGT released from apoptotic endothelial cells acts as a vital progenitor of Ang II to accelerate vascular remodelling, and we suggest that blocking local augmented Ang II might be an effective strategy for restraining intimal hyperplasia.

  3. Supernova Remnant Progenitor Masses in M31

    CERN Document Server

    Jennings, Zachary G; Murphy, Jeremiah W; Dalcanton, Julianne J; Gilbert, Karoline M; Dolphin, Andrew E; Fouesneau, Morgan; Weisz, Daniel R

    2012-01-01

    Using HST photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main sequence masses (MZAMS) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and use CMD fitting to measure the recent star formation history (SFH) of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star and assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the MZAMS from this age. Because our technique is not contingent on precise location of the progenitor star, it can be applied to the location of any known SNR. We identify significant young SF around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of 2 increase over currently measured progenitor masses. We consider the remaining 6 SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped ...

  4. Vascular oxidant stress and inflammation in hyperhomocysteinemia.

    Science.gov (United States)

    Papatheodorou, Louisa; Weiss, Norbert

    2007-11-01

    Elevated plasma levels of homocysteine are a metabolic risk factor for atherosclerotic vascular disease, as shown in numerous clinical studies that linked elevated homocysteine levels to de novo and recurrent cardiovascular events. High levels of homocysteine promote oxidant stress in vascular cells and tissue because of the formation of reactive oxygen species (ROS), which have been strongly implicated in the development of atherosclerosis. In particular, ROS have been shown to cause endothelial injury, dysfunction, and activation. Elevated homocysteine stimulates proinflammatory pathways in vascular cells, resulting in leukocyte recruitment to the vessel wall, mediated by the expression of adhesion molecules on endothelial cells and circulating monocytes and neutrophils, in the infiltration of leukocytes into the arterial wall mediated by increased secretion of chemokines, and in the differentiation of monocytes into cholesterol-scavenging macrophages. Furthermore, it stimulates the proliferation of vascular smooth muscle cells followed by the production of extracellular matrix. Many of these events involve redox-sensitive signaling events, which are promoted by elevated homocysteine, and result in the formation of atherosclerotic lesions. In this article, we review current knowledge about the role of homocysteine on oxidant stress-mediated vascular inflammation during the development of atherosclerosis.

  5. ETS Transcription Factor ETV2/ER71/Etsrp in Hematopoietic and Vascular Development.

    Science.gov (United States)

    Sumanas, S; Choi, K

    2016-01-01

    Effective establishment of the hematopoietic and vascular systems is prerequisite for successful embryogenesis. The ETS transcription factor Etv2 has proven to be essential for hematopoietic and vascular development. Etv2 expression marks the onset of the hematopoietic and vascular development and its deficiency leads to an absolute block in hematopoietic and vascular development. Etv2 is transiently expressed during development and is mainly expressed in testis in adults. Consistent with its expression pattern, Etv2 is transiently required for the generation of the optimal levels of the hemangiogenic cell population. Deletion of this gene after the hemangiogenic progenitor formation leads to normal hematopoietic and vascular development. Mechanistically, ETV2 induces the hemangiogenic program by activating blood and endothelial cell lineage specifying genes and enhancing VEGF signaling. Moreover, ETV2 establishes an ETS hierarchy by directly activating other Ets genes, which in the face of transient Etv2 expression, presumably maintain blood and endothelial cell program initiated by ETV2 through an ETS switching mechanism. Current studies suggest that the hemangiogenic progenitor population is exclusively sensitive to ETV2-dependent FLK1 signaling. Any perturbation in the ETV2, VEGF, and FLK1 balance causing insufficient hemangiogenic progenitor cell generation would lead to defects in hematopoietic and endothelial cell development.

  6. Identification of Endothelial Progenitor Cells in the Corpus Cavernosum in Rats

    Directory of Open Access Journals (Sweden)

    Jun Sik Lee

    2014-01-01

    Full Text Available The vascular wall resident progenitor cells seem to serve as a local reservoir of cells for vascular repair. It was hypothesized that the corpus cavernosum may contain vascular wall endothelial progenitor cells (EPCs. In this study, we investigated the identification and localization of EPCs in the corpus cavernosum in a rat model. Adult male Sprague-Dawley rats were used to isolate EPCs from corpora cavernosum. To verify the existence and localization of EPCs, EPC-specific markers (CD34, Flk-1, and VE-cadherin were evaluated by flow cytometric analysis and confocal microscopy. The EPC markers were mainly expressed in the cavernosal sinusoidal endothelial space. EPC-marker-positive cells made up about 3.31% of the corpus cavernosum of normal rat by FACS analysis. As shown by confocal microscopy, CD34+/Flk-1+ and CD34+/VE-cadherin+ positive cells existed in the corpus cavernosum. Our findings imply that regulation of corpus cavernosal EPCs may be a new therapeutic strategy in the treatment of erectile dysfunction.

  7. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  8. 代谢综合征患者循环可溶性凝素样氧化低密度脂蛋白受体1与血管功能障碍的相关性%The correlation between circulating soluble lectin-like oxidized low-density lipoprotein respector-1 and the vascular dysfunction in patients with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    李爱群; 罗承锋; 李国强; 区文超; 田朝伟; 钟赟; 刘彬; 吴晓蔓

    2015-01-01

    目的:探讨代谢综合征(MS)患者血浆中可溶性凝素样氧化低密度脂蛋白受体1(sLOX-1)与血管功能障碍的关系。方法根据诊断及排除标准按随机数法从256例随访居民中抽取56例作为研究对象,其中MS患者27例( MS组),非MS患者29例( NMS组),动脉硬化测量仪测量颈股脉搏波传导速度( CFPWV),ELISA试剂盒检测血浆中sLOX-1的含量。结果 MS组sLOX-1含量高于NMS组( P<0.05);sLOX-1与CFPWV及体质指数(BMI)呈正相关(CFPWV:r=0.272,P<0.05;BMI:r=0.545,P<0.01),与高密度脂蛋白呈负相关(r=-0.35,P<0.01);线性逐步回归分析显示年龄、血糖及sLOX-1对CFPWV有明显影响。结论 sLOX-1与MS患者血管功能损伤程度密切相关。%Objective To study correlation between circulating soluble lectin-like oxidized low-density lipo-protein respector-1 (sLOX-1) and the vascular dysfunction in patients with metabolic syndrome (MS).Methods Fifty-six subjects were randomly selected from community residents according to diagnostic and exclusion criteria, among whom 27 patients with MS (MS group) and 29 as controls (control group).The carotid pulse wave conduction velocity ( CFPWV) was measured with arterial stiffness measuring instrument, while sLOX-1 was assessed with ELISA kits.Re-sults The sLOX-1 in MS group was significantly higher than control group (P<0.05).The sLOX-1 was also signifi-cantly positively correlated with CFPWV and body mass index (BMI) (CFPWV:r=0.272, P<0.05;BMI:r=0.545, P<0.01), and negatively correlated with high-density lipoprotein (r=0.35, P<0.01).According to linear stepwise regression analysis, age, blood sugar and sLOX-1 had a significant effect on CFPWV.Conclusion SLOX-1 is closely related to vascular function in patients with MS.

  9. The Effect of Heparin-VEGF Multilayer on the Biocompatibility of Decellularized Aortic Valve with Platelet and Endothelial Progenitor Cells

    OpenAIRE

    Xiaofeng Ye; Haozhe Wang; Jingxin Zhou; Haiqing Li; Jun Liu; Zhe Wang; Anqing Chen; Qiang Zhao

    2013-01-01

    The application of polyelectrolyte multilayer films is a new, versatile approach to surface modification of decellularized tissue, which has the potential to greatly enhance the functionality of engineered tissue constructs derived from decellularized organs. In the present study, we test the hypothesis that Heparin- vascular endothelial growth factor (VEGF) multilayer film can not only act as an antithrombotic coating reagent, but also induce proliferation of endothelial progenitor cells (EP...

  10. Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Annalisa Pezzolo; Silvia Deaglio; Fabio Malavasi; Vito Pistoia; Federica Parodi; Danilo Marimpietri; Lizzia Raffaghello; Claudia Cocco; Angela Pistorio; Manuela Mosconi; Claudio Gambini; Michele Cillj

    2011-01-01

    Neuroblastoma (NB)-associated endothelial microvessels (EMs) may be lined by tumor-derived endothelial cells (TECs),that are genetically unstable and chemoresistant.Here we have addressed the identification of TEC progenitors in NB by focusing on Octamer-binding transcription factor 4 (Oct-4) as a putative marker.Oct-4+ cells were detected in primary NB samples (n = 23),metastatic bone marrow aspirates (n = 10),NB cell lines (n = 4),and orthotopic tumors (n = 10) formed by the HTLA-230 NB cell line in immunodeficient mice.Most Oct-4+ cells showed a perivascular distribution,with 5% of them homing in perinecrotic areas.All Oct-4+ cells were tumor-derived since they shared amplification of MYCN oncogene with malignant cells.Perivascular Oct-4+ cells expressed stem cellrelated,neural progenitor-related and NB-related markers,including surface Tenascin C (TNC),that was absent from perinecrotic Oct-4+ cells and bulk tumor cells.TNC+ but not TNC- HTLA-230 cells differentiated in vitro into endothelial-like cells expressing vascular-endothellal-cadherin,prostate-specific membrane antigen and CD31 upon culture in medium containing vascular endothelial growth factor (VEGF).TNC+ but not TNC- HTLA-230 cells formed neurospheres when cultured in serum-free medium.Both cell fractions were tumorigenic,but only tumors formed by TNC+ cegs contained EMs fined by TECs.In conclusion,we have identified in NB tumors two putative niches containing Oct-4+ tumor cells.Oct-4+/TNC+ perivascular NB cells displayed a high degree of plasticity and served as progenitors of TECs.Therapeutic targeting of Oct4+/TNC+ progenitors may counteract the contribution of NB-derived ECs to tumor relapse and chemoresistance.

  11. Vascularity in thyroid neoplasms

    DEFF Research Database (Denmark)

    Larsen, Karen Kjaer; Andersen, Niels Frost; Melsen, Flemming;

    2006-01-01

    The aim of the present study was to evaluate the reliability of four different methods (vascular grading, Chalkley count, microvessel density (MVD) and stereological estimation) for quantifying intratumoral microvascularity in thyroid neoplasms, by comparing the variability within and between...... count should be the preferred method for assessing microvascularity in thyroid neoplasms. The diagnostic evaluation revealed a tendency towards higher degree of vascularity in FA compared to both FC and PC for all methods. No statistically significant association was seen between vascular density and...

  12. Vascular cognitive impairment

    OpenAIRE

    Rebecca F. Gottesman; Hillis, Argye E.

    2014-01-01

    The term vascular cognitive impairment (VCI) has been proposed to encompass all people with cognitive impairment of cerebrovascular origin. VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. VCI forms a spectrum that includes vascular dementia, mixed Alzheimer’s disease with a vascular component, and VCI that does not meet dementia criteria. Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main ...

  13. The Epidemiology of Vascular Dysfunction Relating to Chronic Obstructive Pulmonary Disease and Emphysema

    OpenAIRE

    Barr, R Graham

    2011-01-01

    Cor pulmonale has long been described in very severe chronic obstructive pulmonary disease (COPD) and emphysema. Cross-sectional results from population-based studies show that left ventricular filling and a variety of vascular measures in the systemic circulation are abnormal in preclinical COPD and emphysema and that a predominant vascular change in COPD and emphysema is endothelial and microvascular dysfunction. These findings suggest that pulmonary vascular changes may occur early in COPD...

  14. Specialized mouse embryonic stem cells for studying vascular development

    Directory of Open Access Journals (Sweden)

    Glaser DE

    2014-10-01

    Full Text Available Drew E Glaser,1 Andrew B Burns,2 Rachel Hatano,2 Magdalena Medrzycki,3 Yuhong Fan,3 Kara E McCloskey1 1School of Engineering, University of California, Merced, CA, USA; 2School of Natural Sciences, University of California, Merced, CA, USA; 3School of Biology and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USAAbstract: Vascular progenitor cells are desirable in a variety of therapeutic strategies; however, the lineage commitment of endothelial and smooth muscle cell from a common progenitor is not well-understood. Here, we report the generation of the first dual reporter mouse embryonic stem cell (mESC lines designed to facilitate the study of vascular endothelial and smooth muscle development in vitro. These mESC lines express green fluorescent protein (GFP under the endothelial promoter, Tie-2, and Discomsoma sp. red fluorescent protein (RFP under the promoter for alpha-smooth muscle actin (α-SMA. The lines were then characterized for morphology, marker expression, and pluripotency. The mESC colonies were found to exhibit dome-shaped morphology, alkaline phosphotase activity, as well as expression of Oct 3/4 and stage-specific embryonic antigen-1. The mESC colonies were also found to display normal karyotypes and are able to generate cells from all three germ layers, verifying pluripotency. Tissue staining confirmed the coexpression of VE (vascular endothelial-cadherin with the Tie-2 GFP+ expression on endothelial structures and smooth muscle myosin heavy chain with the α-SMA RFP+ smooth muscle cells. Lastly, it was verified that the developing mESC do express Tie-2 GFP+ and α-SMA RFP+ cells during differentiation and that the GFP+ cells colocalize with the vascular-like structures surrounded by α-SMA-RFP cells. These dual reporter vascular-specific mESC permit visualization and cell tracking of individual endothelial and smooth muscle cells over time and in multiple dimensions, a

  15. Arterial vascular properties in individuals with spina bifida.

    NARCIS (Netherlands)

    Boot, C.R.L.; Langen, H. van; Hopman, M.T.E.

    2003-01-01

    STUDY DESIGN: Observational cross-sectional study. OBJECTIVE: To assess the vascular characteristics of the arterial circulation in individuals with spina bifida (SB) in comparison with individuals with spinal cord injury (SCI) and able-bodied controls (C). SETTING: University Medical Centre, Nijmeg

  16. 补肾益气和活血祛瘀中药治疗血管性痴呆的实验研究%Experimental study of Chinese herbs for replenishing kidney, benefiting qi,activating blood circulation to remove stasis in treatment of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    张宾辉; 代建峰; 陈眉; 丰素娟

    2004-01-01

    背景:血管性痴呆( vascular dementia,VD)是老年期痴呆中常见的一种.补肾益气法、活血祛瘀法是治疗 VD的常用中医治疗方法.而对这两种方法的比较研究尚少. 目的:比较补肾益气方、活血祛瘀方对血管性痴呆大鼠的治疗作用,并探讨中药治疗血管性痴呆大鼠的机制. 设计:完全随机设计,对照实验研究. 地点与材料:地点为浙江省中医院脑病研究室.材料为清洁级健康成年雄性 SD大鼠 75只,鼠龄 18~ 20月,体质量 (400± 30) g.由浙江省中医学院实验动物中心提供并饲养. 方法:采用双侧颈总动脉永久性结扎造成血管性痴呆大鼠模型,并观察药物对该大鼠模型的学习记忆能力,海马 CA1区锥体细胞的形态及数量的影响. 结果:①补肾益气组大鼠跳台测试成绩,造模前( 2.24± 0.17) s,造模用药后 59 d( 2.73± 0.34) s, 造模用药后 60 d( 2.35± 0.28) s.活血祛瘀组大鼠跳台测试成绩,造模前( 2.41± 0.57) s, 造模用药后 59 d( 2.62± 0.41) s, 造模用药后 60 d( 2.34± 0.44) s.补肾益气方,活血祛瘀方可明显改善血管性痴呆大鼠学习记忆能力.②补肾益气方,活血祛瘀方有减轻缺血对海马 CA1区锥体细胞损伤的作用. 结论:①中药补肾益气方、活血祛瘀方为治疗血管性痴呆大鼠的有效方,但活血祛瘀方的治疗作用更好.②活血祛瘀方治疗血管性痴呆大鼠的机制可能与减轻缺血对海马 CA1区椎体细胞的损伤有关.%BACKGROUND:Vascular dementia(VD)is commonly seen in senile dementia.The methods of replenishing kidney and benefiting qi and activating blood circulation to remove stasis are the common therapies in treatment of VD with Chinese medicine.But there are fewer researches on the comparison of the two methods. OBJECTIVE:To compare the effects of the recipe for replenishing kidney and benefiting qi(Recipe No.1)and the recipe of activating blood circulation to remove stasis(Recipe No.2)and

  17. Progenitors of core-collapse supernovae

    CERN Document Server

    Smartt, Stephen J

    2009-01-01

    Knowledge of the progenitors of core-collapse supernovae is a fundamental component in understanding the explosions. The recent progress in finding such stars is reviewed. The minimum initial mass that can produce a supernova has converged to 8 +/- 1 solar masses, from direct detections of red supergiant progenitors of II-P SNe and the most massive white dwarf progenitors, although this value is model dependent. It appears that most type Ibc supernovae arise from moderate mass interacting binaries. The highly energetic, broad-lined Ic supernovae are likely produced by massive, Wolf-Rayet progenitors. There is some evidence to suggest that the majority of massive stars above ~20 solar masses may collapse quietly to black-holes and that the explosions remain undetected. The recent discovery of a class of ultra-bright type II supernovae and the direct detection of some progenitor stars bearing luminous blue variable characteristics suggests some very massive stars do produce highly energetic explosions. The phys...

  18. [Vascular graft prosthesis].

    Science.gov (United States)

    Chakfé, N; Dieval, F; Thaveau, F; Rinckenbach, S; Hassani, O; Camelot, G; Durand, B; Kretz, J-G

    2004-06-01

    Performed since the 1950s, vascular grafting has opened modern era of vascular surgery. Autologous venous grafts are of first choice for revascularisation of small arteries. Synthetic grafts are mainly modelled using microporous polytetrafluoroethylene or terephtalate polyethylene. These prosthesis are mainly used for revascularization of medium and large size arteries. PMID:15220107

  19. Testosterone Enhances the Proliferation of Peripheral-Blood-Derived Endothelial Progenitor Cells by up-regulating Vascular Endothelial Growth Factor Expression%睾酮通过上调血管内皮生长因子表达促进外周血内皮祖细胞增殖

    Institute of Scientific and Technical Information of China (English)

    薛亚威; 任国庆; 王芝; 孙文文; 张浩

    2013-01-01

    目的 探讨雄激素对外周血内皮祖细胞(PB-EPC,)增殖能力的影响及其可能机制.方法 将健康志愿者外周血经密度梯度离心法分离的单个核细胞接种至人纤维连接蛋白包被的培养板中,EGM-2MV培养7天后,多波长激光共聚焦显微镜鉴定FITC标记的荆豆凝集素和Dil标记的乙酰化低密度脂蛋白双染色阳性为PB-EPC.将贴壁细胞分为5组,前4组分别加入0、1、10、100nmol/L睾酮,第5组加入10 nmol/L雄激素受体阻断剂氟他胺干预3h后,再加10 nmol/L睾酮干预.培养48 h后,MTT比色法检测各组PB-EPC的增殖能力.实时定量PCR检测血管内皮生长因子(VEGF) mRNA的表达变化,ELISA检测VEGF分泌量的变化.结果 睾酮呈浓度依赖性促进EPC增殖,雄激素受体阻断剂氟他胺完全阻断睾酮对EPC的促进作用.与空白对照组相比,睾酮在mRNA和蛋白水平上调PB-EPC的VEGF表达,氟他胺可阻断此作用.结论 睾酮通过雄激素受体途径上调VEGF的表达,促进PB-EPC增殖.%Aim To explore the effects and related mechanisms of testosterone on the proliferation of Peripheral-blood endothelial progenitor cells (PB-EPCs). Methods Total mononuclear cells(MNC) were isolated from peripheral blood of healthy volunteers by Ficoll density gradient centrifugation, culturing with EGM-2MV for 7 days in vitro. The adherent cells showed up taking of acetylated low-density ( ac-LDL-Dil) and binding of lectin ( FITC-UEA-I) , observing with confocal laser scanning microscopy. PB-EPC were dealt with four concentrations of testosterone, as 0 nmol/L, 1 nmol/L, 10 nmol/L,and 100 nmol/L respectively, and in another group PB-EPC were pretreated with 10 nmol/L flutamide (androgen receptor antagonist) for 3h and then stimulated with 10 nmol/L testosterone. After 48 h, the ability of cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diph-phenyltetrazolium bromide assay ( MTT). The VEGF expression was tested by quantitative real

  20. Mountains and Tropical Circulation

    Science.gov (United States)

    Naiman, Z.; Goodman, P. J.; Krasting, J. P.; Malyshev, S.; Russell, J. L.; Stouffer, R. J.

    2015-12-01

    Observed tropical convection exhibits zonal asymmetries that strongly influence spatial precipitation patterns. The drivers of changes to this zonally-asymmetric Walker circulation on decadal and longer timescales have been the focus of significant recent research. Here we use two state-of-the-art earth system models to explore the impact of earth's mountains on the Walker circulation. When all land-surface topography is removed, the Walker circulation weakens by 33-59%. There is a ~30% decrease in global, large-scale upward vertical wind velocities in the middle of the troposphere, but only minor changes in global average convective mass flux, precipitation, surface and sea-surface temperatures. The zonally symmetric Hadley circulation is also largely unchanged. Following the spatial pattern of changes to large-scale vertical wind velocities, precipitation becomes less focused over the tropics. The weakening of the Walker circulation, but not the Hadley circulation, is similar to the behavior of climate models during radiative forcing experiments: in our simulations, the weakening is associated with changes in vertical wind velocities, rather than the hydrologic cycle. These results indicate suggest that mountain heights may significantly influence the Walker circulation on geologic time scales, and observed changes in tropical precipitation over millions of years may have been forced by changes in tropical orography.

  1. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  2. 肾移植患者外周血来源的血管内皮祖细胞的促血管新生作用研究%The angiogenic mechanisms of endothelial progenitor cells from the peripheral circulation in kidney transplantation patients

    Institute of Scientific and Technical Information of China (English)

    宋一萌; 李明真; 马潞林

    2016-01-01

    Objective To explore the angiogenic function of EPC from peripheral blood in kidney transplanted patient and to reveal its regulative mechanism.Methods 23 chronic renal failure patients without diabetes were recruited in department of Urology Peking University Third Hospital from January 2014 to February 2015.Fasting peripheral blood mixed with heparin (20 U/mL) was collected one day before and 24 hours after kidney transplantation.We set preoperative blood as control and the postoperative blood as the experimental group.EPC from peripheral blood were isolated by density-gradient centrifugation.FACS was used to identify the EPC.The AA metabolites PGE2 in EPC cultured medium was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Q-PCR and WB were used to detect the expression of endothelial markers in HUVEC cultured under the EPC conditional medium.Tube formation assay was performed to assess the angiogenic ability of HUVEC.Results EPC from kidney transplantation expressed c-kit and CD31 by FACS analysis.Multiple types of AA metabolites was detected in the conditional medium by LC-MS/MS and level of PGE2 increased into two folds after kidney transplantation, compared with that before operation(P < 0.05).HUVEC highly expressed CD31 and VE-cadherin cultured under conditional medium, which were 1.5 folds compared with that before operation (P < 0.01).And those cells formed more tubes than that in control group, which showed better angiogenic capacity.HUVEC, treated by PGE2, had the similar biological characteristics like the conditional culture.Conclusions EPCs in the peripheral blood form kidney transplantation patient secret the PGE2, which can enhance the capacity of angiogenesis in HUVEC.%目的 探讨肾移植患者术后外周血中血管内皮祖细胞(endothelial progenitor cell,EPC)间接调控内皮细胞血管新生过程的作用和机制.方法 2014年1月至2015年2月收治的23例不合并糖尿病的慢性肾衰

  3. A Case of Abnormal Lymphatic-Like Differentiation and Endothelial Progenitor Cell Activation in Neovascularization Associated with Hemi-Retinal Vein Occlusion

    Directory of Open Access Journals (Sweden)

    Sirpa Loukovaara

    2015-07-01

    Full Text Available Purpose: Pathological vascular differentiation in retinal vein occlusion (RVO-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or endothelial progenitor cell activity has not been studied in this disease. Methods: Vitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1, podoplanin (PDPN, and prospero-related homeobox protein 1 (Prox-1. Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67 and expression of the stem cell marker CD117. Results: The specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity. Conclusions: Intraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO.

  4. Adiponectin as a potential biomarker of vascular disease

    Directory of Open Access Journals (Sweden)

    Ebrahimi-Mamaeghani M

    2015-01-01

    Full Text Available Mehrangiz Ebrahimi-Mamaeghani,1 Somayeh Mohammadi,2 Seyed Rafie Arefhosseini,3 Parviz Fallah,4 Zahra Bazi5 1Nutrition Research Center, 2Department of Nutrition, 3Department of Food Technology, Faculty of Nutrition Sciences, Tabriz University of Medical Sciences, Tabriz, 4Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, 5Department of Biotechnology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranAbstract: The increasing prevalence of diabetes and its complications heralds an alarming situation worldwide. Obesity-associated changes in circulating adiponectin concentrations have the capacity to predict insulin sensitivity and are a link between obesity and a number of vascular diseases. One obvious consequence of obesity is a decrease in circulating levels of adiponectin, which are associated with cardiovascular disorders and associated vascular comorbidities. Human and animal studies have demonstrated decreased adiponectin to be an independent risk factor for cardiovascular disease. However, in animal studies, increased circulating adiponectin alleviates obesity-induced endothelial dysfunction and hypertension, and also prevents atherosclerosis, myocardial infarction, and diabetic cardiac tissue disorders. Further, metabolism of a number of foods and medications are affected by induction of adiponectin. Adiponectin has beneficial effects on cardiovascular cells via its antidiabetic, anti-inflammatory, antioxidant, antiapoptotic, antiatherogenic, vasodilatory, and antithrombotic activity, and consequently has a favorable effect on cardiac and vascular health. Understanding the molecular mechanisms underlying the regulation of adiponectin secretion and signaling is critical for designing new therapeutic strategies. This review summarizes the recent evidence for the physiological role and clinical significance of adiponectin in vascular health, identification of

  5. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  6. Vascular sphingolipids in physiological and pathological adaptation.

    Science.gov (United States)

    Bao, Jun-Xiang; Su, Yu-Ting; Cheng, Yao-Ping; Zhang, Hai-Jun; Xie, Xiao-Ping; Chang, Yao-Ming

    2016-01-01

    Sphingolipids (SLs) are compounds containing a long-chain fatty alcohol amine called sphingosine which exists in cellular membranes, cytoplasm, nucleus, interstitial fluid, blood and lymphatic circulation. SLs act as essential constituents of membranes of eukaryotic cells, so the seesaw of SLs will lead to structural alteration of membranes instigating cellular functional change. SLs also act as crucial signaling molecules taking effect intracellularly or extracellularly which regulates activity of downstream molecules determining cellular adaptation to numerous stimulus. This review aims to highlight the contribution of SLs to physiological and pathophysiological remodeling of vasculature. We will first provide a short overview on metabolism, trafficking and compartmentalization of SLs. Then the regulation of SLs on reactive oxygen species (ROS) formation, vascular tone modulation, endothelial barrier integrity, apoptosis and autophagy are summarized. Finally, we will discuss how the SLs are modulated contributing to vascular development, angiogenesis and vascular remodeling in pathological situations as hypertension, atherosclerosis, and aging. The compellingly regulative actions of SLs bring about copious therapeutic targets for potential pharmacological intervention on the diseases involving vascular maladaptation. PMID:27100498

  7. [Transcranial electrostimulation in chronic cerebral vascular insufficiency].

    Science.gov (United States)

    Voropaev, A A; Mochalov, A D

    2006-01-01

    The method of transcranial electrostimulation (TCES) has been used for treatment of 68 patients with chronic cerebral vascular insufficiency, stages I and II. A treatment course included 7 daily procedures. The influence of TCES was evaluated clinically, by EEG, transcranial ultrasonic Doppler study and hemodynamic indices in arteries and veins as well as by expression of trait and state anxiety. All the parameters were compared to those of the control group which was treated using conventional methods. TCES resulted in normalization of cerebral vascular reactivity, a decrease of venous circulation disturbances, positive influence on cerebral blood flow and EEG parameters, that corresponded to global improvement of the patients' state, regress of cephalgic syndrome and reduction of trait and state anxiety. The method is simple and safety and can be recommended for wide application including outpatient setting.

  8. Pigment Cell Progenitors in Zebrafish Remain Multipotent through Metamorphosis.

    Science.gov (United States)

    Singh, Ajeet Pratap; Dinwiddie, April; Mahalwar, Prateek; Schach, Ursula; Linker, Claudia; Irion, Uwe; Nüsslein-Volhard, Christiane

    2016-08-01

    The neural crest is a transient, multipotent embryonic cell population in vertebrates giving rise to diverse cell types in adults via intermediate progenitors. The in vivo cell-fate potential and lineage segregation of these postembryonic progenitors is poorly understood, and it is unknown if and when the progenitors become fate restricted. We investigate the fate restriction in the neural crest-derived stem cells and intermediate progenitors in zebrafish, which give rise to three distinct adult pigment cell types: melanophores, iridophores, and xanthophores. By inducing clones in sox10-expressing cells, we trace and quantitatively compare the pigment cell progenitors at four stages, from embryogenesis to metamorphosis. At all stages, a large fraction of the progenitors are multipotent. These multipotent progenitors have a high proliferation ability, which diminishes with fate restriction. We suggest that multipotency of the nerve-associated progenitors lasting into metamorphosis may have facilitated the evolution of adult-specific traits in vertebrates. PMID:27453500

  9. Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan.

    Directory of Open Access Journals (Sweden)

    Lucia Cuppini

    Full Text Available BACKGROUND: Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF. Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA and classical antiblastic chemotherapy (n=14, independent dataset B: IDB. METHODS: rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. RESULTS: A baseline count of CD109+ CEC higher than 41.1/ml (1(st quartile was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008 and overall survival (OS; 32 versus 23 weeks, P=0.03. Longer PFS (25 versus 8 weeks, P=0.02 and OS (27 versus 17 weeks, P=0.03 were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease at baseline was an independent predictor of shorter PFS and OS (P<0.001. CONCLUSIONS: Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab.

  10. Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Iversen, Lars; Østergaard, O; Ullman, S;

    2013-01-01

    Microparticles (MPs) may be involved in the pathogenesis of systemic sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and coagulation activation. Circulating MPs from SSc patients were characterized and their relationship with soluble markers of vascular activation inves...

  11. Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jun-ichi Kawabe

    2014-01-01

    Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

  12. Pediatric vascular access

    International Nuclear Information System (INIS)

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  13. Pediatric vascular access

    Energy Technology Data Exchange (ETDEWEB)

    Donaldson, James S. [Northwestern University, Feinberg School of Medicine, Department of Medical Imaging, Children' s Memorial Hospital, Chicago, IL (United States)

    2006-05-15

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  14. Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes.

    Directory of Open Access Journals (Sweden)

    Wojciech Wojakowski

    2005-12-01

    Full Text Available Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC. These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD. There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens, as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear

  15. Determination of the optical properties of vascular tissues: potential applications in vascular-targeting photodynamic therapy

    Science.gov (United States)

    Tian, Yongbin; Chen, Ping; Lin, Lie; Huang, Zheng; Tang, Guoqing; Xu, Heping

    2007-11-01

    It has been proven that photodynamic therapy (PDT) is effective in treating various malignant and non-malignant diseases. In the treatment of certain non-malignant vascular diseases, such as wet age-related macular degeneration (AMD) and port wine stains (PWS), unlike in the treatment of malignant solid tumors, light irradiation usually starts immediately after the intravenous (IV) injection of photosensitizers while the photosensitizers is mainly circulating inside blood vessels. Under such vascular-targeting action mode, photoreactions between photosensitizers and light can selectively destruct the vascular tissues. Light distribution is complex so that it is important to understand the optical properties of targeted vessels and surrounding tissues. To better determine the optical properties of vascular tissues, we developed a tissue-simulating phantom and adopted frequency-domain measurement of phase difference. Absorption and reduced scattering coefficients in blood vessels were estimated and light distribution was simulated by the Monte Carlo method. These determinations are essential for the implication of better light dosimetry models in clinical photodynamic therapy and vascular-targeting PDT, in particular.

  16. Design of biomimetic vascular grafts with magnetic endothelial patterning.

    Science.gov (United States)

    Fayol, Delphine; Le Visage, Catherine; Ino, Julia; Gazeau, Florence; Letourneur, Didier; Wilhelm, Claire

    2013-01-01

    The development of small diameter vascular grafts with a controlled pluricellular organization is still needed for effective vascular tissue engineering. Here, we describe a technological approach combining a tubular scaffold and magnetically labeled cells to create a pluricellular and organized vascular graft, the endothelialization of which could be monitored by MRI prior to transplantation. A novel type of scaffold was developed with a tubular geometry and a porous bulk structure enabling the seeding of cells in the scaffold pores. A homogeneous distribution of human mesenchymal stem cells in the macroporous structure was obtained by seeding the freeze-dried scaffold with the cell suspension. The efficient covering of the luminal surface of the tube was then made possible thanks to the implementation of a magnetic-based patterning technique. Human endothelial cells or endothelial progenitors were magnetically labeled with iron oxide nanoparticles and successfully attracted to the 2-mm lumen where they attached and formed a continuous endothelium. The combination of imaging modalities [fluorescence imaging, histology, and 3D magnetic resonance imaging (MRI)] evidenced the integrity of the vascular construct. In particular, the observation of different cell organizations in a vascular scaffold within the range of resolution of single cells by 4.7 T MRI is reported. PMID:23295155

  17. Impact of Endothelial Microparticles on Coagulation, Inflammation, and Angiogenesis in Age-Related Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Margaret Markiewicz

    2013-01-01

    Full Text Available Endothelial microparticles (EMPs are complex vesicular structures that originate from plasma membranes of activated or apoptotic endothelial cells. EMPs play a significant role in vascular function by altering the processes of inflammation, coagulation, and angiogenesis, and they are key players in the pathogenesis of several vascular diseases. Circulating EMPs are increased in many age-related vascular diseases such as coronary artery disease, peripheral vascular disease, cerebral ischemia, and congestive heart failure. Their elevation in plasma has been considered as both a biomarker and bioactive effector of vascular damage and a target for vascular diseases. This review focuses on the pleiotropic roles of EMPs and the mechanisms that trigger their formation, particularly the involvement of decreased estrogen levels, thrombin, and PAI-1 as major factors that induce EMPs in age-related vascular diseases.

  18. Endothelial Progenitor Cells in Peripheral Blood of Cardiac Catheterization Personnel

    Directory of Open Access Journals (Sweden)

    Soheir Korraa1, Tawfik M.S.1, Mohamed Maher 2 and Amr Zaher

    2014-07-01

    Full Text Available Background: The aim of the present study was to evaluate the rejuvenation capacity among cardiac catheterization technicians occupationally exposed to ionizing radiation. Subjects and methods: The individual annual collective dose information was measured by thermoluminscent personal dosimeters (TLD for those technicians and found to be ranging between 2.16 and 8.44 mSv/y. Venous blood samples were obtained from 30 cardiac catheterization technicians exposed to X-ray during fluoroscopy procedures at the National Heart Institute in Embaba. The control group involved 25 persons not exposed to ionizing radiation and not working in hospitals in addition to 20 persons not exposed to ionizing radiation and working in hospitals. Blood samples were assayed for total and differential blood counts, micronucleus formation (FMN plasma stromal derived growth factor-1α (SDF-1 α and cell phenotype of circulating endothelial progenitor cells (EPCs, whose surface markers were identified as the CD34, CD133 and kinase domain receptors (KDR. Results: SDF-1α (2650± 270 vs. 2170 ± 430 pg/ml and FMN (19.9 ± 5.5 vs. 2.8 ± 1.4/1000 cells were significantly higher among cardiac catheterization staff compared to those of the controls respectively. Similarly, EPCs: CD34 (53 ± 3.9 vs. 48 ± 8.5/105 mononuclear cells, CD133 (62.4 ± 4.8 vs. 54.2 ± 10.6 /105 mononuclear cells KDR (52.7 ± 10.6 vs.43.5± 8.2 /105 mononuclear cells were also significantly higher among cardiac catheterization staff compared to the values of controls respectively. Smoking seemed to have a positive effect on the FMN and SDF-1 but had a negative effect on EPCs. It was found that among cardiac catheterization staff, the numbers of circulating progenitor cells had increased and accordingly there was an increased capacity for tissue repair. Conclusion: In conclusion, the present work shows that occupational exposure to radiation, well within permissible levels, leaves a genetic mark on the

  19. Eotaxin-Rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response.

    Science.gov (United States)

    Asosingh, Kewal; Vasanji, Amit; Tipton, Aaron; Queisser, Kimberly; Wanner, Nicholas; Janocha, Allison; Grandon, Deepa; Anand-Apte, Bela; Rothenberg, Marc E; Dweik, Raed; Erzurum, Serpil C

    2016-03-01

    Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole-lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge and before airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and a murine model of asthma. Ex vivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wild-type mice transplanted with eotaxin-1/2-deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, whereas adoptive transfer of proangiogenic progenitor cells from wild-type mice in an atopic asthma model into the eotaxin-1/2-deficient mice led to angiogenesis and airway inflammation. The findings indicate that Th2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation. PMID:26810221

  20. Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

    Directory of Open Access Journals (Sweden)

    P. Alvarez

    2013-01-01

    Full Text Available Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a the role of different factors, such as stromal cell derived factor-1 (SDF-1, granulocyte colony-stimulating factor (G-CSF, and vascular cell adhesion molecule-1 (VCAM-1, among other ligands; (b the stem cell count in peripheral blood and BM and influential factors; (c the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

  1. In vivo identification of periodontal progenitor cells.

    Science.gov (United States)

    Roguljic, H; Matthews, B G; Yang, W; Cvija, H; Mina, M; Kalajzic, I

    2013-08-01

    The periodontal ligament contains progenitor cells; however, their identity and differentiation potential in vivo remain poorly characterized. Previous results have suggested that periodontal tissue progenitors reside in perivascular areas. Therefore, we utilized a lineage-tracing approach to identify and track periodontal progenitor cells from the perivascular region in vivo. We used an alpha-smooth muscle actin (αSMA) promoter-driven and tamoxifen-inducible Cre system (αSMACreERT2) that, in combination with a reporter mouse line (Ai9), permanently labels a cell population, termed 'SMA9'. To trace the differentiation of SMA9-labeled cells into osteoblasts/cementoblasts, we utilized a Col2.3GFP transgene, while expression of Scleraxis-GFP was used to follow differentiation into periodontal ligament fibroblasts during normal tissue formation and remodeling following injury. In uninjured three-week-old SMA9 mice, tamoxifen labeled a small population of cells in the periodontal ligament that expanded over time, particularly in the apical region of the root. By 17 days and 7 weeks after labeling, some SMA9-labeled cells expressed markers indicating differentiation into mature lineages, including cementocytes. Following injury, SMA9 cells expanded, and differentiated into cementoblasts, osteoblasts, and periodontal ligament fibroblasts. SMA9-labeled cells represent a source of progenitors that can give rise to mature osteoblasts, cementoblasts, and fibroblasts within the periodontium. PMID:23735585

  2. Binary progenitor models of type IIb supernovae

    NARCIS (Netherlands)

    Claeys, J.S.W.A.; de Mink, S.E.; Pols, O.R.; Eldridge, J.J.; Baes, M.

    2011-01-01

    Massive stars that lose their hydrogen-rich envelope down to a few tenths of a solar mass explode as extended type IIb supernovae, an intriguing subtype that links the hydrogen-rich type II supernovae with the hydrogen-poor type Ib and Ic. The progenitors may be very massive single stars that lose t

  3. GRB 011121 A Massive Star Progenitor

    CERN Document Server

    Price, P A; Reichart, D E; Kulkarni, S R; Subramanian, R; Wark, R M; Wieringa, M H; Frail, D A; Bailey, J; Boyle, B; Corbett, E A; Gunn, K; Ryder, S D; Seymour, N; Koviak, K; McCarthy, P; Phillips, M; Axelrod, T S; Bloom, J S; Djorgovski, S G; Fox, D W; Galama, T J; Harrison, F A; Hurley, K; Sari, R; Schmidt, B P; Yost, S A; Brown, M J I; Cline, T; Frontera, F; Guidorzi, C; Montanari, E

    2002-01-01

    Of the cosmological gamma-ray bursts, GRB 011121 has the lowest redshift, z=0.36. More importantly, the multi-color excess in the afterglow detected in the Hubble Space Telescope (HST) light curves is compelling observational evidence for an underlying supernova. Here we present near-infrared and radio observations of the afterglow. We undertake a comprehensive modeling of these observations and those reported in the literature and find good evidence favoring a wind-fed circumburst medium. In detail, we infer the progenitor had a mass loss rate of Mdot ~ 10^-7 / v_w3 Mo/yr where v_w3 is the speed of the wind from the progenitor in units of 10^3 km/s. This mass loss rate is similar to that inferred for the progenitor of SN 1998bw which has been associated with GRB 980425. Our data, taken in conjunction with the HST results of Bloom et al. (2002), provide a consistent picture: the long duration GRB 011121 had a massive star progenitor which exploded as a supernova at about the same time as the GRB event.

  4. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  5. Congenital Vascular Malformation

    Science.gov (United States)

    ... clots, obstruction of major vessels, causing progressive limb asymmetry by overgrowth, and for cosmetic indications or because ... t he Vascular Disease Foundation (VDF) develops educational information and initiatives for patients, their families and friends, ...

  6. Heart and vascular services

    Science.gov (United States)

    ... Repair of aneurysms (dilated/enlarged portions) of the aorta and its branches Procedures may also be used ... Nutrition and lifestyle counseling, including smoking cessation and diabetes education Supervised exercise Alternative Names Circulatory system; Vascular ...

  7. Recombinant human granulocyte colony-stimulating factor increases circulating CD34-postive cells in patients with AIDS

    DEFF Research Database (Denmark)

    Nielsen, S D; Dam-Larsen, S; Nielsen, C;

    1997-01-01

    circulating hematopoietic progenitor cells (CD34 cells) in patients with AIDS, using the recombinant human granulocyte colony-stimulating factor (G-CSF). Eight patients with AIDS were treated with G-CSF for neutropenia (< 1.0 x 10(9)/l). Treatment consisted of daily subcutaneous injections with 300 micrograms...

  8. Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study

    Directory of Open Access Journals (Sweden)

    Stubbs Andrew

    2009-08-01

    Full Text Available Abstract Background Endothelial progenitor cells play an important role in vascular wall repair. Patients with type 1 diabetes have reduced levels of endothelial progenitor cells of which their functional capacity is impaired. Reduced nitric oxide bioavailability and increased oxidative stress play a role in endothelial progenitor cell dysfunction in these patients. Folic acid, a B-vitamin with anti-oxidant properties, may be able to improve endothelial progenitor cell function. In this study, we investigated the gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes compared to endothelial progenitor cells from healthy subjects. Furthermore, we studied the effect of folic acid on gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes. Methods We used microarray analysis to investigate the gene expression profiles of endothelial progenitor cells from type 1 diabetes patients before (n = 11 and after a four week period of folic acid supplementation (n = 10 compared to the gene expression profiles of endothelial progenitor cells from healthy subjects (n = 11. The probability of genes being differentially expressed among the classes was computed using a random-variance t-test. A multivariate permutation test was used to identify genes that were differentially expressed among the two classes. Functional classification of differentially expressed genes was performed using the biological process ontology in the Gene Ontology database. Results Type 1 diabetes significantly modulated the expression of 1591 genes compared to healthy controls. These genes were found to be involved in processes regulating development, cell communication, cell adhesion and localization. After folic acid treatment, endothelial progenitor cell gene expression profiles from diabetic patients were similar to those from healthy controls. Genes that were normalized by folic acid played a prominent role in

  9. Human cerebral circulation. Positron emission tomography studies

    International Nuclear Information System (INIS)

    We reviewed the literature on human cerebral circulation and oxygen metabolism, as measured by positron emission tomography (PET), with respect to normal values and of regulation of cerebral circulation. A multicenter study in Japan showed that between-center variations in cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) values were not considerably larger than the corresponding within-center variations. Overall mean±SD values in cerebral cortical regions of normal human subjects were as follows: CBF=44.4±6.5 ml/100 ml/min; CBV=3.8±0.7 ml/100 ml; OEF=0.44±0.06; CMRO2=3.3±0.5 ml/100 ml/min (11 PET centers, 70 subjects). Intrinsic regulation of cerebral circulation involves several factors. Autoregulation maintains CBF in response to changes in cerebral perfusion pressure; chemical factors such as PaCO2 affect cerebral vascular tone and alter CBF; changes in neural activity cause changes in cerebral energy metabolism and CBF; neurogenic control of CBF occurs by sympathetic innervation. Regional differences in vascular response to changes in PaCO2 have been reported, indicating regional differences in cerebral vascular tone. Relations between CBF and CBV during changes in PaCO2 and during changes in neural activity were in good agreement with Poiseuille's law. The mechanisms of vascular response to neural activation and deactivation were independent on those of responses to PaCO2 changes. CBV in a brain region is the sum of three components: arterial, capillary and venous blood volumes. It has been reported that the arterial blood volume fraction is approximately 30% in humans and that changes in human CBV during changes in PaCO2 are caused by changes in arterial blood volume without changes in venous blood volume. These findings should be considered in future studies of the pathophysiology of cerebrovascular diseases. (author) 136 refs

  10. 房颤对外周血CD34+造血祖细胞的影响 及SDF-1/CXCR4在心房中的表达%Effect of atrial fibrillation on human CD34 + hematopoietic progenitor cells in circulation and expression of SDF-1/CXCR4 in atrium

    Institute of Scientific and Technical Information of China (English)

    李佳; 葛海龙; 陈光远; 高倩萍; 孙俊峰; 李元十; 富路

    2011-01-01

    目的:研究不同类型的房颤(AF)对人外周血CD34+造血祖细胞(CD34+ HPCs)的影响,以及持续心房快速起搏犬心肌基质细胞衍生因子-1(SDF-1)及其受体CXCR4的表达,初步探讨CD34+ HPCs及SDF-1/CXCR4在AF时心肌损伤修复中的作用.方法:应用流式细胞术测定阵发性AF患者组(a=35)、持续性AF患者组(n=35)及窦性心律者对照组(n=30)外周血中CD34+ HPCs的百分含量;并对持续性AF患者组中24例患者成功进行体外直流电复律后48 h,测定外周血中CD34+ HPCs的百分含量.另外,将成年健康杂种犬13条随机分为两组:即快速起搏组(n=7)和假手术组(n=6),均开胸后于右心耳缝植AOO型起搏器,快速起搏组以400次/min起搏6周,假手术组不起搏.应用RT-PCR测定左心耳和左心房CXCR4mRNA的表达水平,用蛋白质免疫印迹法检测左心房SDF-1蛋白的表达.结果:持续性AF患者组外周血中CD34+ HPCs的百分含量明显高于阵发性AF患者组和对照组(P<0.05);而后两组间无差别.持续性AF患者成功进行体外直流电复律后48 h,外周血中CD34+ HPCs的百分含量较复律前明显下降(P<0.05).快速起搏组犬左心耳和左心房CXCR4mRNA表达的水平明显高于假手术组(P<0.05),左心耳增高16.7%,左心房增高18.8%:SDF-1蛋白质表达的水平亦明显高于假手术组(P<0.01).结论:持续性AF患者外周血中CD34 HPCs的数量增加;心房快速起搏犬心房SDF-1/CXCR4的表达增加.CD34+ HPCs和SDF1/CXCR4可能参与了持续性AF患者心房损伤时心肌组织的修复过程.%AIM: To investigate the effect of different kinds of atrial fibrillation (AF) on human CD34 + hematopoietic cells ( HPCs) in circulation and on myocardial expression of SDF-1 and its receptor CXCR4 in canines with lasting rapid atrial pacing and to explore the role of CD34 + HPCs and SDF-1/ CXCR4 in repairing atrium during AF. METHODS; Included in our study were 100 subjects (35 with paroxysmal AF, 35

  11. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

    Directory of Open Access Journals (Sweden)

    Cai-Guo Yu

    2016-01-01

    Full Text Available Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

  12. Thrombolysis in vascular surgery

    OpenAIRE

    Smith, Linn

    2015-01-01

    Background and aims: Thrombolysis is in common use in the treatment of acute forms of vascular disease. It may be used both systemically and locally, in the latter case through an endovascular approach, socalled catheter-directed thrombolysis. The aims of this thesis were to investigate how thrombolysis affects performance-related outcomes pertaining to vascular patency after thrombolysis, and how it affects patient safety and the development of complications. Metho...

  13. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks.

    Science.gov (United States)

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  14. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    Science.gov (United States)

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  15. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks.

    Directory of Open Access Journals (Sweden)

    Tae-Yun Kang

    Full Text Available We used indirect stereolithography (SL to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture.

  16. Cell Therapy for Diabetic Neuropathy Using Adult Stem or Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Ji Woong Han

    2013-04-01

    Full Text Available Diabetic neuropathy (DN is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.

  17. Vascular endothelial growth factor: a neurovascular target in neurological diseases.

    Science.gov (United States)

    Lange, Christian; Storkebaum, Erik; de Almodóvar, Carmen Ruiz; Dewerchin, Mieke; Carmeliet, Peter

    2016-08-01

    Brain function critically relies on blood vessels to supply oxygen and nutrients, to establish a barrier for neurotoxic substances, and to clear waste products. The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, but was later co-opted by blood vessels to regulate vascular function. Consequently, VEGF represents an attractive target to modulate brain function at the neurovascular interface. On the one hand, VEGF is neuroprotective, through direct effects on neural cells and their progenitors and indirect effects on brain perfusion. In accordance, preclinical studies show beneficial effects of VEGF administration in neurodegenerative diseases, peripheral neuropathies and epilepsy. On the other hand, pathologically elevated VEGF levels enhance vessel permeability and leakage, and disrupt blood-brain barrier integrity, as in demyelinating diseases, for which blockade of VEGF may be beneficial. Here, we summarize current knowledge on the role and therapeutic potential of VEGF in neurological diseases. PMID:27364743

  18. Gaussian Fibonacci Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices have become important tools in solving integrable system, Hamiltonian structure, and integral equations. In this paper, we prove that Gaussian Fibonacci circulant type matrices are invertible matrices for n>2 and give the explicit determinants and the inverse matrices. Furthermore, the upper bounds for the spread on Gaussian Fibonacci circulant and left circulant matrices are presented, respectively.

  19. Biophysical Properties of Scaffolds Modulate Human Blood Vessel Formation from Circulating Endothelial Colony-Forming Cells

    Science.gov (United States)

    Critser, Paul J.; Yoder, Mervin C.

    A functional vascular system forms early in development and is continually remodeled throughout the life of the organism. Impairment to the regeneration or repair of this system leads to tissue ischemia, dysfunction, and disease. The process of vascular formation and remodeling is complex, relying on local microenvironmental cues, cytokine signaling, and multiple cell types to function properly. Tissue engineering strategies have attempted to exploit these mechanisms to develop functional vascular networks for the generation of artificial tissues and therapeutic strategies to restore tissue homeostasis. The success of these strategies requires the isolation of appropriate progenitor cell sources which are straightforward to obtain, display high proliferative potential, and demonstrate an ability to form functional vessels. Several populations are of interest including endothelial colony-forming cells, a subpopulation of endothelial progenitor cells. Additionally, the development of scaffolds to deliver and support progenitor cell survival and function is crucial for the formation of functional vascular networks. The composition and biophysical properties of these scaffolds have been shown to modulate endothelial cell behavior and vessel formation. However, further investigation is needed to better understand how these mechanical properties and biophysical properties impact vessel formation. Additionally, several other cell populations are involved in neoangiogenesis and formation of tissue parenchyma and an understanding of the potential impact of these cell populations on the biophysical properties of scaffolds will also be needed to advance these strategies. This chapter examines how the biophysical properties of matrix scaffolds can influence vessel formation and remodeling and, in particular, the impact on in vivo human endothelial progenitor cell vessel formation.

  20. Pure midbrain ischemia and hypoplastic vertebrobasilar circulation.

    Science.gov (United States)

    Gilberti, Nicola; Gamba, Massimo; Costa, Angelo; Vergani, Veronica; Spezi, Raffaella; Pezzini, Alessandro; Volonghi, Irene; Mardighian, Dikran; Gasparotti, Roberto; Padovani, Alessandro; Magoni, Mauro

    2014-02-01

    Isolated midbrain infarction is rare and little is known about etiology and patient's long-term follow up. We aimed to describe the clinical features, the causative diseases and the outcome of patients with isolated midbrain infarction who were admitted to our center, focusing on vascular abnormalities of posterior circulation. All patients with first acute ischemic stroke limited to the midbrain were included and their demographic features, neurological symptoms, neuroimaging data, and cardiovascular risk factors were recorded. Functional outcome, using modified Rankin scale, was assessed at discharge and at the 3 month follow up evaluation. We found nine patients with acute isolated midbrain infarction, representing 0.61 % of all ischemic stroke admitted to our center. The most common cause of stroke was small-vessel disease (88.8 %). At stroke onset, none of the patients had consciousness disturbances, and four patients (44.4 %) had gait impairment, five patients (55.5 %) presented with diplopia due to involvement of the third nerve or fascicular type of third-nerve palsy, seven patients (77.7 %) had vascular anomalies of vertebrobasilar circulation: the most frequent was vertebral artery hypoplasia [four patients (44.4 %)]. At follow up evaluation, seven patients (77.7 %) had a good functional outcome and no patients experienced recurrence of cerebrovascular events. As isolated midbrain infarction is uncommon, specific ocular motor signs, mainly third-nerve palsy, may help to identify and localize the mesencephalic infarct. Abnormalities in vertebrobasilar circulation, such as hypoplastic basilar or vertebral artery, are frequently associated with isolated midbrain ischemia. The hypoplastic vertebrobasilar system may predispose to posterior ischemic stroke.

  1. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  2. Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells.

    Science.gov (United States)

    Celebi, Betül; Mantovani, Diego; Pineault, Nicolas

    2011-10-01

    Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

  3. Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Celebi, Betuel; Pineault, Nicolas [Hema-Quebec, Research and Development Department, Quebec City, G1V 5C3, PQ (Canada); Mantovani, Diego, E-mail: nicolas.pineault@hema-quebec.qc.ca [Laboratory for Biomaterials and Bioengineering, Department of Materials Engineering and University Hospital Research Center, Laval University, Quebec City, G1V 0A6, PQ (Canada)

    2011-10-15

    Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

  4. In vitro differentiation of porcine aortic vascular precursor cells to endothelial and vascular smooth muscle cells.

    Science.gov (United States)

    Zaniboni, Andrea; Bernardini, Chiara; Bertocchi, Martina; Zannoni, Augusta; Bianchi, Francesca; Avallone, Giancarlo; Mangano, Chiara; Sarli, Giuseppe; Calzà, Laura; Bacci, Maria Laura; Forni, Monica

    2015-09-01

    Recent findings suggest that progenitor and multipotent mesenchymal stromal cells (MSCs) are associated with vascular niches. Cells displaying mesenchymal properties and differentiating to whole components of a functional blood vessel, including endothelial and smooth muscle cells, can be defined as vascular stem cells (VSCs). Recently, we isolated a population of porcine aortic vascular precursor cells (pAVPCs), which have MSC- and pericyte-like properties. The aim of the present work was to investigate whether pAVPCs possess VSC-like properties and assess their differentiation potential toward endothelial and smooth muscle lineages. pAVPCs, maintained in a specific pericyte growth medium, were cultured in high-glucose DMEM + 10% FBS (long-term medium, LTM) or in human endothelial serum-free medium + 5% FBS and 50 ng/ml of hVEGF (endothelial differentiation medium, EDM). After 21 days of culture in LTM, pAVPCs showed an elongated fibroblast-like morphology, and they seem to organize in cord-like structures. qPCR analysis of smooth muscle markers [α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin (SMM) heavy chain] showed a significant increment of the transcripts, and immunofluorescence analysis confirmed the presence of α-SMA and SMM proteins. After 21 days of culture in EDM, pAVPCs displayed an endothelial cell-like morphology and revealed the upregulation of the expression of endothelial markers (CD31, vascular endothelial-cadherin, von Willebrand factor, and endothelial nitric oxide synthase) showing the CD31-typical pattern. In conclusion, pAVPCs could be defined as a VSC-like population considering that, if they are maintained in a specific pericyte medium, they express MSC markers, and they have, in addition to the classical mesenchymal trilineage differentiation potential, the capacity to differentiate in vitro toward the smooth muscle and the endothelial cell phenotypes. PMID:26135800

  5. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies. PMID:26585821

  6. Circulant Double Coverings of a Circulant Graph of Valency Five

    Institute of Scientific and Technical Information of China (English)

    Rong Quan FENG; Jin Ho KWAK

    2007-01-01

    Enumerating the isomorphism classes of several types of graph covering projections is one of the central research topics in enumerative topological graph theory. A covering of G is called circulant if its covering graph is circulant. Recently, the authors [Discrete Math., 277, 73-85 (2004)]enumerated the isomorphism classes of circulant double coverings of a certain type, called a typicalcovering, and showed that no double covering of a circulant graph of valency three is circulant. Also, in [Graphs and Combinatorics, 21, 386-400 (2005)], the isomorphism classes of circulant double coverings of a circulant graph of valency four are enumerated. In this paper, the isomorphism classes of circulant double coverings of a circulant graph of valency five are enumerated.

  7. [Vasomotor reactions of the pulmonary circulation upon hypothalamic stimulation].

    Science.gov (United States)

    Tsybenko, V A; Guinh-van-Tam

    1977-01-01

    The blood flow in the lung lobe perfused under constant pressure was recorded with photoelectric drop recorder in acute closed-chest experiments in anesthetized dogs. Stimulation of supraoptic and lateral mamillary nuclei in most cases decreased flow rate and increased vascular resistance in perfused pulmonary lobe, while stimulation of sympatho-inhibitory area exerted opposite effect. Bilateral vagotomy and administration of atropin and inderal did not block the lesser circulation responses to the hypothalamic stimulation. However, phentolamine and bilateral ablation of stellate and upper thoracic ganglia eliminated chnages of blood flow and vascular resistance in the perfused lobe. The data obtained suggest that stimulation of some hypothalamic areas evoke obvious vasomotor responses in the lesser circulation and that these responses occur mainly through alpha-adrenergic sympathetic innervation of pulmonary vessels. PMID:832755

  8. Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

    Science.gov (United States)

    Park, Susanna S

    2016-04-01

    Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

  9. Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD

    OpenAIRE

    Schlieper, Georg; Westenfeld, Ralf; Krüger, Thilo; Cranenburg, Ellen C.; Magdeleyns, Elke J.; Brandenburg, Vincent M.; Djuric, Zivka; Damjanovic, Tatjana; Ketteler, Markus; Vermeer, Cees; Dimkovic, Nada; Floege, Jürgen; Schurgers, Leon J.

    2011-01-01

    The mechanisms for vascular calcification and its associated cardiovascular mortality in patients with ESRD are not completely understood. Dialysis patients exhibit profound vitamin K deficiency, which may impair carboxylation of the calcification inhibitor matrix gla protein (MGP). Here, we tested whether distinct circulating inactive vitamin K–dependent proteins associate with all-cause or cardiovascular mortality. We observed higher levels of both desphospho-uncarboxylated MGP (dp-ucMGP) a...

  10. Cardiovascular studies in the rhesus monkey. [brain circulation during stress

    Science.gov (United States)

    Stone, H. L.; Sandler, H.

    1977-01-01

    Criteria are given for selecting the macaca mulatta as the analogue of the human in the study of cerebral circulation, particularly the control of the cerebral vascular bed during normal and stressful conditions. Topics discussed include surgical preparation of subject; responses to changes in arterial pressure, oxygen, and carbon dioxide; innervation of cerebral vessels; cerebral flow response to acceleration; and cerebral blood flow and cerebellar stimulation.

  11. Physiological modeling of tumor-affected renal circulation.

    OpenAIRE

    Bézy-Wendling, Johanne; Kretowski, Marek

    2008-01-01

    International audience One way of gaining insight into what can be observed in medical images is through physiological modeling. For instance, anatomical and functional modifications occur in the organ during the appearance and the growth of a tumor. Some of these changes concern the vascularization. We propose a computational model of tumor-affected renal circulation that represents the local heterogeneity of different parts of the kidney (cortex, medulla). We present a simulation of vasc...

  12. Doppler velocimetry with emphasis on the fetal cerebral circulation

    OpenAIRE

    Noordam, Marja

    1996-01-01

    textabstractIn this thesis the following questions were addressed: 1. Are changes in placental vascular resistance associated with alterations in arterial down stream impedance at fetal level? To this purpose placental embolization was carried-out in the fetal lamb with subsequent Doppler velocimetry in the fetal descending aorta (chapter 2). 2. What happens to the human fetal cerebral circulation relative to normal and raised umbilical placental resistance? To answer this question, the human...

  13. The endocannabinoid system drives neural progenitor proliferation.

    Science.gov (United States)

    Aguado, Tania; Monory, Krisztina; Palazuelos, Javier; Stella, Nephi; Cravatt, Benjamin; Lutz, Beat; Marsicano, Giovanni; Kokaia, Zaal; Guzmán, Manuel; Galve-Roperh, Ismael

    2005-10-01

    The discovery of multipotent neural progenitor (NP) cells has provided strong support for the existence of neurogenesis in the adult brain. However, the signals controlling NP proliferation remain elusive. Endocannabinoids, the endogenous counterparts of marijuana-derived cannabinoids, act as neuromodulators via presynaptic CB1 receptors and also control neural cell death and survival. Here we show that progenitor cells express a functional endocannabinoid system that actively regulates cell proliferation both in vitro and in vivo. Specifically, NPs produce endocannabinoids and express the CB1 receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase (FAAH). CB1 receptor activation promotes cell proliferation and neurosphere generation, an action that is abrogated in CB1-deficient NPs. Accordingly, proliferation of hippocampal NPs is increased in FAAH-deficient mice. Our results demonstrate that endocannabinoids constitute a new group of signaling cues that regulate NP proliferation and thus open novel therapeutic avenues for manipulation of NP cell fate in the adult brain.

  14. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  15. Noninvasive Imaging of Administered Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90

  16. BMP signaling in the nephron progenitor niche

    OpenAIRE

    Oxburgh, Leif; Brown, Aaron C.; Fetting, Jennifer; Hill, Beth

    2011-01-01

    Bone morphogenic proteins (BMPs) play diverse roles in embryonic kidney development, regulating essential aspects of both ureteric bud and nephron development. In this review, we provide an overview of reported expression patterns and functions of BMP signaling components within the nephrogenic zone or nephron progenitor niche of the developing kidney. Reported in situ hybridization results are relatively challenging to interpret and sometimes conflicting. Comparing these with high-resolution...

  17. Human Fetal Progenitor Tenocytes for Regenerative Medicine.

    OpenAIRE

    Grognuz A.; Scaletta C.; Farron A.; Raffoul W.; Applegate L.A.

    2016-01-01

    Tendon injuries are very frequent and affect a wide and heterogeneous population. Unfortunately, the healing process is long with outcomes that are not often satisfactory due to fibrotic tissue appearance, which leads to scar and adhesion development. Tissue engineering and cell therapies emerge as interesting alternatives to classical treatments. In this study, we evaluated human fetal progenitor tenocytes (hFPTs) as a potential cell source for treatment of tendon afflictions, as fetal cells...

  18. TOX3 regulates neural progenitor identity.

    Science.gov (United States)

    Sahu, Sanjeeb Kumar; Fritz, Alina; Tiwari, Neha; Kovacs, Zsuzsa; Pouya, Alireza; Wüllner, Verena; Bora, Pablo; Schacht, Teresa; Baumgart, Jan; Peron, Sophie; Berninger, Benedikt; Tiwari, Vijay K; Methner, Axel

    2016-07-01

    The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromatin immunoprecipitation assays. In line with this, over-expression of Tox3 increased Nestin promoter activity, which was cooperatively enhanced by treatment with the stem cell self-renewal promoting Notch ligand Jagged and repressed by pharmacological inhibition of Notch signaling. Knockdown of Tox3 in the subventricular zone of E12.5 mouse embryos by in utero electroporation of Tox3 shRNA revealed a reduced Nestin expression and decreased proliferation at E14 and a reduced migration to the cortical plate in E16 embryos in electroporated cells. Together, these results argue for a role of Tox3 in the development of the nervous system. PMID:27080130

  19. Endothelial progenitor cells in hematologic malignancies.

    Science.gov (United States)

    Testa, Ugo; Saulle, Ernestina; Castelli, Germana; Pelosi, Elvira

    2016-01-01

    Studies carried out in the last years have improved the understanding of the cellular and molecular mechanisms controlling angiogenesis during adult life in normal and pathological conditions. Some of these studies have led to the identification of some progenitor cells that sustain angiogenesis through indirect, paracrine mechanisms (hematopoietic angiogenic cells) and through direct mechanisms, i.e., through their capacity to generate a progeny of phenotypically and functionally competent endothelial cells [endothelial colony forming cells (ECFCs)]. The contribution of these progenitors to angiogenetic processes under physiological and pathological conditions is intensively investigated. Angiogenetic mechanisms are stimulated in various hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma, resulting in an increased angiogenesis that contributes to disease progression. In some of these conditions there is preliminary evidence that some endothelial cells could derive from the malignant clone, thus leading to the speculation that the leukemic cell derives from the malignant transformation of a hemangioblastic progenitor, i.e., of a cell capable of differentiation to the hematopoietic and to the endothelial cell lineages. Our understanding of the mechanisms underlying increased angiogenesis in these malignancies not only contributed to a better knowledge of the mechanisms responsible for tumor progression, but also offered the way for the discovery of new therapeutic targets. PMID:27583252

  20. Circulating Endothelial Cells in Patients with Heart Failure and Left Ventricular Dysfunction

    Directory of Open Access Journals (Sweden)

    Vicenta Martínez-Sales

    2011-01-01

    Full Text Available Introduction and Aims: Acute and chronic heart failure may manifest different degrees of endothelial damage and angiogenesis. Circulating endothelial cells (CEC have been identified as marker of vascular damage. The aim of our study was to evaluate the evolution of the CEC at different stages of patients with heart failure. We also investigated a potential correlation between CEC and markers of vascular damage and angiogenesis.

  1. 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1

    OpenAIRE

    Shimoda, Larissa A.

    2012-01-01

    When exposed to chronic hypoxia (CH), the pulmonary circulation responds with enhanced contraction and vascular remodeling, resulting in elevated pulmonary arterial pressures. Our work has identified CH-induced alterations in the expression and activity of several ion channels and transporters in pulmonary vascular smooth muscle that contribute to the development of hypoxic pulmonary hypertension and uncovered a critical role for the transcription factor hypoxia-inducible factor-1 (HIF-1) in ...

  2. Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

    Directory of Open Access Journals (Sweden)

    Rie Kawabe-Yako

    Full Text Available BACKGROUND: Cilostazol(CLZ has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM-derived endothelial progenitor cell (EPC contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for

  3. Vascular Endothelial Growth Factor, diagnostic and therapeutic aspects

    OpenAIRE

    Kusumanto, Yoka Hadiani

    2006-01-01

    This thesis focuses on the diagnostic and therapeutic potential of Vascular Endothelial Growth Factor, an angiogenic growth factor. Since the recognition of VEGF’s pivotal role in physiological and pathological angiogenesis research has evolved from cell culture and animal experiments to application in humans. The studies described in this thesis aim to contribute to the evaluation of circulating VEGF as a surrogate marker in the quantification of angiogenesis and of the therapeutic role of V...

  4. Plant vascular development

    NARCIS (Netherlands)

    Rybel, De Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate

  5. Engineered Vascularized Muscle Flap.

    Science.gov (United States)

    Egozi, Dana; Shandalov, Yulia; Freiman, Alina; Rosenfeld, Dekel; Ben-Shimol, David; Levenberg, Shulamit

    2016-01-01

    One of the main factors limiting the thickness of a tissue construct and its consequential viability and applicability in vivo, is the control of oxygen supply to the cell microenvironment, as passive diffusion is limited to a very thin layer. Although various materials have been described to restore the integrity of full-thickness defects of the abdominal wall, no material has yet proved to be optimal, due to low graft vascularization, tissue rejection, infection, or inadequate mechanical properties. This protocol describes a means of engineering a fully vascularized flap, with a thickness relevant for muscle tissue reconstruction. Cell-embedded poly L-lactic acid/poly lactic-co-glycolic acid constructs are implanted around the mouse femoral artery and vein and maintained in vivo for a period of one or two weeks. The vascularized graft is then transferred as a flap towards a full thickness defect made in the abdomen. This technique replaces the need for autologous tissue sacrifications and may enable the use of in vitro engineered vascularized flaps in many surgical applications. PMID:26779840

  6. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  7. Asymmetric centrosome inheritance maintains neural progenitors in neocortex

    OpenAIRE

    Wang, Xiaoqun; Tsai, Jin-Wu; Imai, Janice H.; Lian, Wei-Nan; Vallee, Richard B.; Shi, Song-Hai

    2009-01-01

    Asymmetric divisions of radial glial progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. While differentiating cells leave the VZ to constitute the future neocortex, renewing radial glial progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these beh...

  8. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  9. INTERNAL CIRCULATION ENVELOPES

    CERN Multimedia

    Mail Office

    2001-01-01

    Internal mail envelopes often finish up in large piles in certain offices, thus creating a shortage for other users of the mail service, who would be grateful if everyone with an unused stock could deposit them in their mail box, after attaching them together with an elastic band or a piece of string. The messengers will then collect them so that the Mail Office can put them back in circulation. Thank you for your understanding and collaboration.

  10. Vascular manifestations of Behcet's disease

    Directory of Open Access Journals (Sweden)

    Regina Georgiyeva Goloeva

    2010-04-01

    Conclusion. Vascular disorders in BD were diagnosed in one fourth of the patients, mainly in young male patients. Severe thromboses with the development of chronic venous insignificance, Budd-Chiari syndrome, pulmonary and iliac artery aneurysms, and arterial thromboses were observed in male patients only. Vascular events were associated with erythema nodosum and epididymitis; in these concomitances, the vascular risk was substantially increased. Vascular death rates were 2,2%.

  11. [Harvey and his theory of circulation].

    Science.gov (United States)

    Wolters, Frank J

    2013-01-01

    In 1628 the English physician William Harvey (1578-1657) published his revolutionary theory that blood circulates through the body driven by the heart. This challenged the long-standing teachings of Hippocrates and Galen concerning 4 different bodily fluids or 'humours' that flowed through separate arterial and venous vascular systems. Harvey gained considerable influence in society as a member of the prestigious Royal College of Physicians in London and as personal physician to King James I and King Charles I. He strove for a more empirical foundation of medicine by means of anatomic demonstrations and vivisections. Despite enduring considerable criticism he managed to disseminate his ideas around the influential universities of Europe in the course of his lifetime. However, consequent changes in practice would not be brought about until decades after Harvey's death, when Galenist treatments such as blood-letting were gradually abandoned.

  12. Monitoring cerebral oxygenation in a pediatric patient undergoing surgery for vascular ring.

    Science.gov (United States)

    Joshi, Reena K; Motta, Pablo; Horibe, Mayumi; Mossad, Emad

    2006-02-01

    Regional cerebral oxygenation can be monitored using near-infrared spectroscopy (NIRS). Inadequacy of collateral cerebral circulation and regional cerebral ischemia during cardiac and vascular surgery may be detected by the use of NIRS monitoring. We report a 2-year-old child who underwent surgical repair of vascular ring and subclavian reimplantation, where use of NIRS helped in early detection and timely intervention to prevent prolonged cerebral ischemia. PMID:16430416

  13. Retinal Endothelial Cell Apoptosis Stimulates Recruitment of Endothelial Progenitor Cells

    Science.gov (United States)

    Bhatwadekar, Ashay D.; Glenn, Josephine V.; Curtis, Tim M.; Grant, Maria B.; Stitt, Alan W.; Gardiner, Tom A.

    2013-01-01

    Purpose Bone marrow–derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair. Methods Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed. Results Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05– 0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-α when compared to control medium; SDF-1 remained unchanged. Conclusions The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment. PMID:19474402

  14. Bone Marrow Stress Decreases Osteogenic Progenitors.

    Science.gov (United States)

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  15. Vascular and endothelial regeneration.

    Science.gov (United States)

    Casteilla, Louis; Planat-Bénard, Valérie; Cousin, Béatrice; Laharrague, Patrick; Bourin, Philippe

    2010-06-01

    Adipose tissue is the final tissue to develop and is strongly involved in energy homeostasis. It can represent up to 50% of body weight in obesity. Beside its metabolic role, endocrine functions appeared to play a key role in interconnecting adipose tissue with other tissues of the organism and in numerous physiological functions. The presence of adipocyte progenitors has long been demonstrated throughout life in the stromal fraction of adipose tissue. Now, it appears that these cells are multipotent and share numerous features with mesenchymal stem cells (MSC) derived from bone marrow. They also display some specificities and a strong pro-angiogenic potential. Altogether, these data emphasize the need to reconsider the potential of adipose tissue. Moreover, since fat pads are easy to sample, numerous and promising perspectives are now opening up in regenerative medicine, particularly in ischemic situations.

  16. Surface modification of a polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer as a stent coating for enhanced capture of endothelial progenitor cells.

    OpenAIRE

    Tan, Aaron; Farhatnia, Yasmin; Goh, Debbie; Natasha, G; de Mel, Achala; Lim, Jing; Teoh, Swee-Hin; Malkovskiy, Andrey V; Chawla, Reema; Rajadas, Jayakumar; Cousins, Brian G; Michael R Hamblin; Alavijeh, Mohammad S; Seifalian, Alexander M

    2013-01-01

    An unmet need exists for the development of next-generation multifunctional nanocomposite materials for biomedical applications, particularly in the field of cardiovascular regenerative biology. Herein, we describe the preparation and characterization of a novel polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer with covalently attached anti-CD34 antibodies to enhance capture of circulating endothelial progenitor cells (EPC). This material may ...

  17. Vascular cognitive impairment and dementia.

    Science.gov (United States)

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  18. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  19. [Vascular endothelial Barrier Function].

    Science.gov (United States)

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  20. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  1. SH2-inositol phosphatase 1 negatively influences early megakaryocyte progenitors.

    Directory of Open Access Journals (Sweden)

    Lia E Perez

    Full Text Available BACKGROUND: The SH2-containing-5'inositol phosphatase-1 (SHIP influences signals downstream of cytokine/chemokine receptors that play a role in megakaryocytopoiesis, including thrombopoietin, stromal-cell-derived-Factor-1/CXCL-12 and interleukin-3. We hypothesize that SHIP might control megakaryocytopoiesis through effects on proliferation of megakaryocyte progenitors (MKP and megakaryocytes (MK. METHODOLOGY AND PRINCIPAL FINDINGS: Herein, we report the megakaryocytic phenotype and MK functional assays of hematopoietic organs of two strains of SHIP deficient mice with deletion of the SHIP promoter/first exon or the inositol phosphatase domain. Both SHIP deficient strains exhibit a profound increase in MKP numbers in bone marrow (BM, spleen and blood as analyzed by flow cytometry (Lin(-c-Kit+CD41+ and functional assays (CFU-MK. SHIP deficient MKP display increased phosphorylation of Signal Transducers and Activators of Transcription 3 (STAT-3, protein kinase B (PKB/AKT and extracellular signal-regulated kinases (ERKs. Despite increased MKP content, total body number of mature MK (Lin(-c-kit(-CD41+ are not significantly changed as SHIP deficient BM contains reduced MK while spleen MK numbers are increased. Reduction of CXCR-4 expression in SHIP deficient MK may influence MK localization to the spleen instead of the BM. Endomitosis, process involved in MK maturation, was preserved in SHIP deficient MK. Circulating platelets and red blood cells are also reduced in SHIP deficient mice. CONCLUSIONS/SIGNIFICANCE: SHIP may play an important role in regulation of essential signaling pathways that control early megakaryocytopoiesis in vivo.

  2. Modelled Circulation In Storfjorden

    Science.gov (United States)

    Skogseth, R.; Asplin, L.

    The model area Storfjorden is situated between the islands Spitsbergen, Barentsöya and Edgeöya at the Svalbard Archipelago. The entrance of Storfjorden is defined by a shallow bank Storfjordbanken and some small islands Tusenöyane in southeast, and by an 115m deep sill at about 76 45' N in the south. Maximum depth in Storfjorden is 190m, which is surrounded by gradually shallower shelves in the north, the east and southeast. A steep bottom slope is present on the western side of Storfjorden. He- leysundet and Freemansundet, two sounds between respectively Spitsbergen and Bar- entsöya, and Barentsöya and Edgeöya, define two narrow and shallow entrances in the north and northeast connecting Storfjorden with the northwestern Barents Sea. Strong tidal currents exist in Heleysundet (4-5ms-1) and Freemansundet (2-3ms-1), but the general circulation in Storfjorden is not well known. The coastal current in Storfjor- den is cyclonic directed into Storfjorden south of Edgeöya from the East Spitsbergen Current and out of Storfjorden south of Spitsbergen where it is called Sørkappstrøm- men. A three-dimensional sigma layered numerical ocean model called Bergen Ocean Model (BOM) was used to simulate the circulation in Storfjorden with Freemansundet opened. Two simulations were carried out, one with heat flux (100 Wm-2) and one without heat flux from the ocean to the atmosphere. The heat flux was applied only in the proper fjord area north of the sill and not outside as a crude approximation of the effects of a polynya in the sea ice cover during winter. Both simulations had a 4km horizontal resolution and 21 sigma layers. The model is forced by winds (from the NCEP reanalyzed fields) and tides. Initial fields are from the DNMI/IMR climatol- ogy. The model simulation without heat flux gave a circulation heavily dependent on tidal forcing, showing strong tidal currents up to 2ms-1 in Freemansundet, between Tusenöyane and on Storfjordbanken southwest of Edgeöya. Earlier

  3. Update on Vascular Dementia.

    Science.gov (United States)

    Khan, Ayesha; Kalaria, Raj N; Corbett, Anne; Ballard, Clive

    2016-09-01

    Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment. PMID:27502303

  4. Resolvability in Circulant Graphs

    Institute of Scientific and Technical Information of China (English)

    Muhammad SALMAN; Imran JAVAID; Muhammad Anwar CHAUDHRY

    2012-01-01

    A set W of the vertices of a connected graph G is called a resolving set for G if for every two distinct vertices u,v ∈ V(G) there is a vertex w ∈ W such that d(u,w) ≠ d(v,w).A resolving set of minimum cardinality is called a metric basis for G and the number of vertices in a metric basis is called the metric dimension of G,denoted by dim(G).For a vertex u of G and a subset S of V(G),the distance between u and S is the number mins∈s d(u,s).A k-partition H ={S1,S2,...,Sk} of V(G) is called a resolving partition if for every two distinct vertices u,v ∈ V(G) there is a set Si in Π such that d(u,Si) ≠ d(v,Si).The minimum k for which there is a resolving k-partition of V(G) is called the partition dimension of G,denoted by pd(G).The circulant graph is a graph with vertex set Zn,an additive group ofintegers modulo n,and two vertices labeled i and j adjacent if and only if i - j (mod n) ∈ C,where C C Zn has the property that C =-C and 0(∈) C.The circulant graph is denoted by Xn,△ where A =|C|.In this paper,we study the metric dimension of a family of circulant graphs Xn,3 with connection set C ={1,-n/2,n - 1} and prove that dim(Xn,3) is independent of choice of n by showing that 3 for all n =0 (mod 4),dim(X,n,3) ={ 4 for all n =2 (mod 4).We also study the partition dimension of a family of circulant graphs Xn,4 with connection set C ={±1,±2} and prove that pd(Xn,4) is independent of choice of n and show that pd(X5,4) =5 and 3 forall odd n≥9,pd(Xn,4) ={ 4 for all even n ≥ 6 and n =7.

  5. Enzymatic regulation of functional vascular networks using gelatin hydrogels.

    Science.gov (United States)

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

    2015-06-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

  6. Galactic Constraints on Supernova Progenitor Models

    CERN Document Server

    Acharova, I; Mishurov, Yu; Kovtyukh, V

    2013-01-01

    We undertake a statistical analysis of the radial abundance distributions in the Galactic disk within a theoretical framework for Galactic chemical evolution which incorporates the influence of spiral arms. 1) The mean mass of oxygen ejected per core-collapse SNe (CC SNe) event (which are concentrated within spiral arms) is $\\sim$0.27 M$_{\\odot}$; 2) the mean mass of iron ejected by `tardy' Type Ia SNe (SNeIa; progenitors of whom are older/longer-lived stars with ages $\\simgt$100 Myr and up to several Gyr, which do not concentrate within spiral arms) is $\\sim$0.58 M$_{\\odot}$; 3) the upper mass of iron ejected by prompt SNeIa (SNe whose progenitors are younger/shorter-lived stars with ages $\\simlt$100 Myr, which are concentrated within spiral arms) is $\\leq$0.23 M$_{\\odot}$ per event; 4) the corresponding mean mass of iron produced by CC SNe is $\\leq$0.04 M$_{\\odot}$ per event; (v) short-lived SNe (core-collapse or prompt SNeIa) supply $\\sim$85% of the Galactic disk's iron. The inferred low mean mass of oxyge...

  7. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors

    OpenAIRE

    Jiang, Huaqi; Edgar, Bruce A.

    2009-01-01

    In holometabolous insects, the adult appendages and internal organs form anew from larval progenitor cells during metamorphosis. As described here, the adult Drosophila midgut, including intestinal stem cells (ISCs), develops from adult midgut progenitor cells (AMPs) that proliferate during larval development in two phases. Dividing AMPs first disperse, but later proliferate within distinct islands, forming large cell clusters that eventually fuse during metamorphosis ...

  8. Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues.

    Science.gov (United States)

    Shan, Tizhong; Liang, Xinrong; Bi, Pengpeng; Zhang, Pengpeng; Liu, Weiyi; Kuang, Shihuan

    2013-08-01

    Brown adipose tissues (BAT) are derived from a myogenic factor 5 (Myf5)-expressing cell lineage and white adipose tissues (WAT) predominantly arise from non-Myf5 lineages, although a subpopulation of adipocytes in some WAT depots can be derived from the Myf5 lineage. However, the functional implication of the Myf5- and non-Myf5-lineage cells in WAT is unclear. We found that the Myf5-lineage constitution in subcutaneous WAT depots is negatively correlated to the expression of classical BAT and newly defined beige/brite adipocyte-specific genes. Consistently, fluorescent-activated cell sorting (FACS)-purified Myf5-lineage adipo-progenitors give rise to adipocytes expressing lower levels of BAT-specific Ucp1, Prdm16, Cidea, and Ppargc1a genes and beige adipocyte-specific CD137, Tmem26, and Tbx1 genes compared with the non-Myf5-lineage adipocytes from the same depots. Ablation of the Myf5-lineage progenitors in WAT stromal vascular cell (SVC) cultures leads to increased expression of BAT and beige cell signature genes. Strikingly, the Myf5-lineage cells in WAT are heterogeneous and contain distinct adipogenic [stem cell antigen 1(Sca1)-positive] and myogenic (Sca1-negative) progenitors. The latter differentiate robustly into myofibers in vitro and in vivo, and they restore dystrophin expression after transplantation into mdx mouse, a model for Duchenne muscular dystrophy. These results demonstrate the heterogeneity and functional differences of the Myf5- and non-Myf5-lineage cells in the white adipose tissue.

  9. Does liver-intestine significantly degrade circulating endogenous substance P in man?

    DEFF Research Database (Denmark)

    Henriksen, J H; Schaffalitzky de Muckadell, Ove B.; Bülow, J B

    1986-01-01

    Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P...... was determined in various vascular beds during a right-sided catheterization in 13 subjects without liver insufficiency. All subjects had normal values of circulating substance P, and no significant difference was found between systemic plasma and hepatic venous or renal venous concentrations of substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....

  10. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    Science.gov (United States)

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID:26141839

  11. Development of Endothelial-Specific Single Inducible Lentiviral Vectors for Genetic Engineering of Endothelial Progenitor Cells.

    Science.gov (United States)

    Yang, Guanghua; Kramer, M Gabriela; Fernandez-Ruiz, Veronica; Kawa, Milosz P; Huang, Xin; Liu, Zhongmin; Prieto, Jesus; Qian, Cheng

    2015-11-27

    Endothelial progenitor cells (EPC) are able to migrate to tumor vasculature. These cells, if genetically modified, can be used as vehicles to deliver toxic material to, or express anticancer proteins in tumor. To test this hypothesis, we developed several single, endothelial-specific, and doxycycline-inducible self-inactivating (SIN) lentiviral vectors. Two distinct expression cassettes were inserted into a SIN-vector: one controlled by an endothelial lineage-specific, murine vascular endothelial cadherin (mVEcad) promoter for the expression of a transactivator, rtTA2S-M2; and the other driven by an inducible promoter, TREalb, for a firefly luciferase reporter gene. We compared the expression levels of luciferase in different vector constructs, containing either the same or opposite orientation with respect to the vector sequence. The results showed that the vector with these two expression cassettes placed in opposite directions was optimal, characterized by a robust induction of the transgene expression (17.7- to 73-fold) in the presence of doxycycline in several endothelial cell lines, but without leakiness when uninduced. In conclusion, an endothelial lineage-specific single inducible SIN lentiviral vector has been developed. Such a lentiviral vector can be used to endow endothelial progenitor cells with anti-tumor properties.

  12. North Atlantic Circulation

    Science.gov (United States)

    Molinari, R.; Bryan, K.; Schott, F.

    The intensity of the North Atlantic winddriven and thermohaline circulation and the close proximity of many oceanographic installations make the North Atlantic a particularly favored region of the world ocean from the standpoint of research in ocean circulation. Recent increases in available data and advances in numerical modeling techniques served as the impetus to convene a joint workshop of modelers and observers working on the North Atlantic with the Scientific Committee on Oceanic Research (SCOR) Working Group (WG) 68 (“North Atlantic Circulation”). Goals of the workshop were to provide an update on data sets and models and to discuss the poleward heat flux problem and possible monitoring strategies. The joint Workshop/SCOR WG-68 meeting was convened by F. Schott (chairman of the working group; Rosenstiel School of Marine and Atmospheric Science, Miami, Fla.), K. Bryan (National Oceanic and Atmospheric Administration/ Geophysical Fluid Dynamics Laboratory (NOAA/GFDL)), and R. Molinari (NOAA/Atlantic Oceanographic and Meteorological Laboratory (NOAA/AOML)).

  13. Circulation of Stars

    Science.gov (United States)

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  14. Effect of human neural progenitor cells on injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    XU Guang-hui; BAI Jin-zhu; CAI Qin-lin; LI Xiao-xia; LI Ling-song; SHEN Li

    2005-01-01

    Objective: To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats.Methods: Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan (BBB) locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry.Results: Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats.Conclusions: Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.

  15. The role of neurosonology in the diagnosis of vascular dementia.

    Science.gov (United States)

    Tsivgoulis, Georgios; Katsanos, Aristeidis H; Papageorgiou, Sokratis G; Dardiotis, Efthimios; Voumvourakis, Konstantinos; Giannopoulos, Sotirios

    2014-01-01

    Although transcranial sonography is not yet an established diagnostic modality for dementia screening or differential diagnosis of Alzheimer's disease (AD) from vascular dementia (VaD), intracranial hemodynamic assessment may provide crucial information about the association between cognitive deterioration and vascular risk factors. We conducted a systematic narrative review of available literature through MEDLINE and EMBASE search to identify all available data about the evaluation of VaD patients with transcranial Doppler, and to discuss further the vascular disorders of the cerebral circulation in patients with vascular cognitive impairment. According to the available literature data to date, VaD patients were found to have lower mean flow velocity values in four studies (indicating cerebral hypoperfusion), higher pulsatility indices in three studies (indicating increased downstream vascular resistance), and more severe impairment of cerebrovascular reactivity in five studies (indicating exhausted vasodilatory reserve) compared to AD patients and controls. Microembolic signals were also found to be significantly more common in patients with VaD or AD compared to their age- and gender-matched controls, suggesting that asymptomatic microembolism, apart for being only marker of VaD, could presumably be involved in the genesis of dementia, and in the overlap between VaD and AD. Further studies with larger and carefully selected groups are required to eliminate potential confounders and to set specific cut-off values for the aforementioned hemodynamic parameters in demented patients and dementia subtypes.

  16. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan

    2012-07-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  17. Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

    Directory of Open Access Journals (Sweden)

    GM Roomans

    2010-06-01

    Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

  18. In Vivo Monitoring of Multiple Circulating Cell Populations Using Two-photon Flow Cytometry.

    Science.gov (United States)

    Tkaczyk, Eric R; Zhong, Cheng Frank; Ye, Jing Yong; Myc, Andrzej; Thomas, Thommey; Cao, Zhengyi; Duran-Struuck, Raimon; Luker, Kathryn E; Luker, Gary D; Norris, Theodore B; Baker, James R

    2008-02-15

    To detect and quantify multiple distinct populations of cells circulating simultaneously in the blood of living animals, we developed a novel optical system for two-channel, two-photon flow cytometry in vivo. We used this system to investigate the circulation dynamics in live animals of breast cancer cells with low (MCF-7) and high (MDA-MB-435) metastatic potential, showing for the first time that two different populations of circulating cells can be quantified simultaneously in the vasculature of a single live mouse. We also non-invasively monitored a population of labeled, circulating red blood cells for more than two weeks, demonstrating that this technique can also quantify the dynamics of abundant cells in the vascular system for prolonged periods of time. These data are the first in vivo application of multichannel flow cytometry utilizing two-photon excitation, which will greatly enhance our capability to study circulating cells in cancer and other disease processes.

  19. Microfluidic Technology in Vascular Research

    Directory of Open Access Journals (Sweden)

    A. D. van der Meer

    2009-01-01

    Full Text Available Vascular cell biology is an area of research with great biomedical relevance. Vascular dysfunction is involved in major diseases such as atherosclerosis, diabetes, and cancer. However, when studying vascular cell biology in the laboratory, it is difficult to mimic the dynamic, three-dimensional microenvironment that is found in vivo. Microfluidic technology offers unique possibilities to overcome this difficulty. In this review, an overview of the recent applications of microfluidic technology in the field of vascular biological research will be given. Examples of how microfluidics can be used to generate shear stresses, growth factor gradients, cocultures, and migration assays will be provided. The use of microfluidic devices in studying three-dimensional models of vascular tissue will be discussed. It is concluded that microfluidic technology offers great possibilities to systematically study vascular cell biology with setups that more closely mimic the in vivo situation than those that are generated with conventional methods.

  20. Ocean General Circulation Models

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jin-Ho; Ma, Po-Lun

    2012-09-30

    1. Definition of Subject The purpose of this text is to provide an introduction to aspects of oceanic general circulation models (OGCMs), an important component of Climate System or Earth System Model (ESM). The role of the ocean in ESMs is described in Chapter XX (EDITOR: PLEASE FIND THE COUPLED CLIMATE or EARTH SYSTEM MODELING CHAPTERS). The emerging need for understanding the Earth’s climate system and especially projecting its future evolution has encouraged scientists to explore the dynamical, physical, and biogeochemical processes in the ocean. Understanding the role of these processes in the climate system is an interesting and challenging scientific subject. For example, a research question how much extra heat or CO2 generated by anthropogenic activities can be stored in the deep ocean is not only scientifically interesting but also important in projecting future climate of the earth. Thus, OGCMs have been developed and applied to investigate the various oceanic processes and their role in the climate system.

  1. Cathepsin L is required for endothelial progenitor cell-induced neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra; Sasaki, Ken-ichiro; Bruhl, Thomas; Hofmann, Wolf K.; Peters, Christoph; Reinheckel, Thomas; Pennacchio, Len A.; Abolmaali, Nasreddin D.; Chavakis, Emmanouil; Zeiher, Andreas M.; Dimmeler, Stefanie

    2004-01-15

    Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sites of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.

  2. Percutaneous interventions in Fontan circulation

    Directory of Open Access Journals (Sweden)

    Eduardo Franco

    2015-09-01

    Conclusions: Interventional catheterization procedures are often necessary to reach and maintain the fragile Fontan circulation, mainly in patients with right morphology systemic ventricles and fenestrated Fontan conduits.

  3. MRI evaluation of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Yicheng Liu; Hongxing Zhang; Wei Huang; Wenjun Wan; Hongfen Peng

    2006-01-01

    OBJECTTVE: To explain the association between vascular dementia and the cranial MRI manifestations, and recognize the value of cranial MRI in the early diagnosis of vascular dementia and the assessment of disease conditions.DATA SOURCES: Pubmed database was searched to identify articles about the cranial MRI manifestations of patients with vascular dementia published in English from January 1992 to June 2006 by using the key words of "MRI, vascular dementia". Others were collected by searching the name of journals and title of articles in the Chinese full-text journal database.STUDY SELECTTON: The collected articles were primarily checked, those correlated with the cranial MRI manifestations of patients with vascular dementia were selected, while the obviously irrelative ones were excluded, and the rest were retrieved manually, the full-texts were searched.DATA EXTRACTION: Totally 255 articles were collected, 41 of them were involved, and the other 214 were excluded.DATA SYNTHESIS: MRI can be taken as one of the effective methods for the early diagnosis and disease evaluation of vascular dementia. White matter lesions are the important risk factors of vascular dementia.Vascular dementia is accompanied by the atrophy of related brain sites, but further confirmation is needed to investigate whether there is significant difference. MRI can be used to quantitatively investigate the infarcted sites and sizes of patients with vascular dementia after infarction, but there is still lack of systematic investigation on the association of the infarcted sites and sizes with the cognitive function of patients with vascular dementia.CONCLUSTON: Cranial MRI can detect the symptoms of vascular dementia at early period, so that corresponding measures can be adopted to prevent and treat vascular dementia in time.

  4. Progenitor model of cosmic ray knee

    Science.gov (United States)

    Bijay, Biplab; Bhadra, Arunava

    2016-01-01

    The primary energy spectrum of cosmic rays exhibits a knee at about 3 PeV where a change in the spectral index occurs. Despite many efforts, the origin of such a feature in the spectrum is not satisfactorily solved yet. Here it is proposed that the steepening of the spectrum beyond the knee may be a consequence of the mass distribution of the progenitor of the cosmic ray source. The proposed speculative model can account for all the major observed features of cosmic rays without invoking any fine tuning to match flux or spectra at any energy point. The prediction of the proposed model regarding the primary composition scenario beyond the knee is quite different from most of the prevailing models of the knee, and thereby can be discriminated from precise experimental measurement of the primary composition.

  5. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  6. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  7. Multipotent pancreas progenitors: Inconclusive but pivotal topic.

    Science.gov (United States)

    Jiang, Fang-Xu; Morahan, Grant

    2015-12-26

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  8. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets

    OpenAIRE

    Möhle, Robert; Green, David; Moore, Malcolm A. S.; Nachman, Ralph L.; Rafii, Shahin

    1997-01-01

    We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors. Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growt...

  9. Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Alexander W Lange

    Full Text Available The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth factor-beta (TGF-beta-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-beta1-mediated transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.

  10. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  11. CT in vascular pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Bartolozzi, C.; Neri, E.; Caramella, D. [Diagnostic and Interventional Radiology Department of Oncology, University of Pisa, Via Roma 67, I-56100 Pisa (Italy)

    1998-06-02

    Since the introduction of helical scanners, CT angiography (CTA) has achieved an essential role in many vascular applications that were previously managed with conventional angiography. The performance of CTA is based on the accurate selection of collimation width, pitch, reconstruction spacing and scan delay, which must be modulated on the basis of the clinical issue. However, the major improvement of CT has been provided by the recent implementation of many post-processing techniques, such as multiplanar reformatting, shaded surface display, maximum intensity projections, 3D perspectives of surface and volume rendering, which simulate virtual intravascular endoscopy. The integration of the potentialities of the scanner and of the image processing techniques permitted improvement of: (a) the evaluation of aneurysms, dissection and vascular anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c) aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has shown that the assessment of arterial pathologies with CTA requires the integration of 3D post-processing techniques in most applications. (orig.) With 4 figs., 34 refs.

  12. Pulmonary vascular diseases.

    Science.gov (United States)

    Mélot, C; Naeije, R

    2011-04-01

    Diseases of the pulmonary vasculature are a cause of increased pulmonary vascular resistance (PVR) in pulmonary embolism, chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary arterial hypertension or decreased PVR in pulmonary arteriovenous malformations on hereditary hemorrhagic telangiectasia, portal hypertension, or cavopulmonary anastomosis. All these conditions are associated with a decrease in both arterial PO2 and PCO2. Gas exchange in pulmonary vascular diseases with increased PVR is characterized by a shift of ventilation and perfusion to high ventilation-perfusion ratios, a mild to moderate increase in perfusion to low ventilation-perfusion ratios, and an increased physiologic dead space. Hypoxemia in these patients is essentially explained by altered ventilation-perfusion matching amplified by a decreased mixed venous PO2 caused by a low cardiac output. Hypocapnia is accounted for by hyperventilation, which is essentially related to an increased chemosensitivity. A cardiac shunt on a patent foramen ovale may be a cause of severe hypoxemia in a proportion of patients with pulmonary hypertension and an increase in right atrial pressure. Gas exchange in pulmonary arteriovenous malformations is characterized by variable degree of pulmonary shunting and/or diffusion-perfusion imbalance. Hypocapnia is caused by an increased ventilation in relation to an increased pulmonary blood flow with direct peripheral chemoreceptor stimulation by shunted mixed venous blood flow. PMID:23737196

  13. No effect of melatonin to modify surgical-stress response after major vascular surgery

    DEFF Research Database (Denmark)

    Kücükakin, B.; Wilhelmsen, M.; Lykkesfeldt, Jens;

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  14. Engineering skeletal muscle tissues from murine myoblast progenitor cells and application of electrical stimulation.

    Science.gov (United States)

    van der Schaft, Daisy W J; van Spreeuwel, Ariane C C; Boonen, Kristel J M; Langelaan, Marloes L P; Bouten, Carlijn V C; Baaijens, Frank P T

    2013-03-19

    Engineered muscle tissues can be used for several different purposes, which include the production of tissues for use as a disease model in vitro, e.g. to study pressure ulcers, for regenerative medicine and as a meat alternative (1). The first reported 3D muscle constructs have been made many years ago and pioneers in the field are Vandenburgh and colleagues (2,3). Advances made in muscle tissue engineering are not only the result from the vast gain in knowledge of biochemical factors, stem cells and progenitor cells, but are in particular based on insights gained by researchers that physical factors play essential roles in the control of cell behavior and tissue development. State-of-the-art engineered muscle constructs currently consist of cell-populated hydrogel constructs. In our lab these generally consist of murine myoblast progenitor cells, isolated from murine hind limb muscles or a murine myoblast cell line C2C12, mixed with a mixture of collagen/Matrigel and plated between two anchoring points, mimicking the muscle ligaments. Other cells may be considered as well, e.g. alternative cell lines such as L6 rat myoblasts (4), neonatal muscle derived progenitor cells (5), cells derived from adult muscle tissues from other species such as human (6) or even induced pluripotent stem cells (iPS cells) (7). Cell contractility causes alignment of the cells along the long axis of the construct (8,9) and differentiation of the muscle progenitor cells after approximately one week of culture. Moreover, the application of electrical stimulation can enhance the process of differentiation to some extent (8). Because of its limited size (8 x 2 x 0.5 mm) the complete tissue can be analyzed using confocal microscopy to monitor e.g. viability, differentiation and cell alignment. Depending on the specific application the requirements for the engineered muscle tissue will vary; e.g. use for regenerative medicine requires the up scaling of tissue size and vascularization, while

  15. Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.

    Science.gov (United States)

    Goichberg, Polina

    2016-08-01

    With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential. PMID:27209167

  16. Distinct Sources of Hematopoietic Progenitors Emerge before HSCs and Provide Functional Blood Cells in the Mammalian Embryo

    Directory of Open Access Journals (Sweden)

    Kathleen E. McGrath

    2015-06-01

    Full Text Available Hematopoietic potential arises in mammalian embryos before adult-repopulating hematopoietic stem cells (HSCs. At embryonic day 9.5 (E9.5, we show the first murine definitive erythro-myeloid progenitors (EMPs have an immunophenotype distinct from primitive hematopoietic progenitors, maturing megakaryocytes and macrophages, and rare B cell potential. EMPs emerge in the yolk sac with erythroid and broad myeloid, but not lymphoid, potential. EMPs migrate to the fetal liver and rapidly differentiate, including production of circulating neutrophils by E11.5. Although the surface markers, transcription factors, and lineage potential associated with EMPs overlap with those found in adult definitive hematopoiesis, they are present in unique combinations or proportions that result in a specialized definitive embryonic progenitor. Furthermore, we find that embryonic stem cell (ESC-derived hematopoiesis recapitulates early yolk sac hematopoiesis, including primitive, EMP, and rare B cell potential. EMPs do not have long-term potential when transplanted in immunocompromised adults, but they can provide transient adult-like RBC reconstitution.

  17. Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

    Science.gov (United States)

    Nana, Yang; Peng, Jiao; Jianlin, Zhang; Xiangjian, Zhang; Shutong, Yao; Enxin, Zhan; Bin, Li; Chuanlong, Zong; Hua, Tian; Yanhong, Si; Yunsai, Du; Shucun, Qin; Hui, Wang

    2015-01-01

    Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

  18. The Coronary Circulation as a Target of Cardioprotection.

    Science.gov (United States)

    Heusch, Gerd

    2016-05-13

    The atherosclerotic coronary vasculature is not only the culprit but also a victim of myocardial ischemia/reperfusion injury. Manifestations of such injury are increased vascular permeability and edema, endothelial dysfunction and impaired vasomotion, microembolization of atherothrombotic debris, stasis with intravascular cell aggregates, and finally, in its most severe form, capillary destruction with hemorrhage. In animal experiments, local and remote ischemic pre- and postconditioning not only reduce infarct size but also these manifestations of coronary vascular injury, as do drugs which recruit signal transduction steps of conditioning. Clinically, no-reflow is frequently seen after interventional reperfusion, and it carries an adverse prognosis. The translation of cardioprotective interventions to clinical practice has been difficult to date. Only 4 drugs (brain natriuretic peptide, exenatide, metoprolol, and esmolol) stand unchallenged to date in reducing infarct size in patients with reperfused acute myocardial infarction; unfortunately, for these drugs, no information on their impact on the ischemic/reperfused coronary circulation is available. PMID:27174955

  19. Developmental expression of vascular endothelial growth factor receptor 3 and vascular endothelial growth factor C in forebrain.

    Science.gov (United States)

    Ward, M C; Cunningham, A M

    2015-09-10

    Increased understanding of the neurovascular niche suggests that development of the central nervous system (CNS) and its vasculature is coordinated through shared regulatory factors. These include the vascular endothelial growth factor (VEGF) family, reported to promote neuroproliferation and neuroprotection in addition to angiogenesis via its receptors VEGFR1-3. VEGFR3, a mediator of lymphangiogenesis, is expressed in murine and rat brain from early gestation, has been associated with neural progenitors and neurons (Choi et al., 2010) and oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al., 2011). The early expression pattern of VEGFR3 protein and its cellular associations has not as yet been comprehensively reported. We describe the temporal expression of VEGFR3 protein at a cellular level and its close association with its VEGFC ligand, determined by double-labeling immunohistochemistry in the developing rat brain from embryonic day (E) 13 to postnatal day (P) 23. We found high expression of VEGFR3 in the ventricular zone and along radial glia in early gestation in association with neural stem cells and neuroblasts. Similar expression patterns were seen in the immature olfactory bulb and optic cup. In later development we found less expression by neural progenitors in proliferative regions including the SVZ and dentate gyrus of the hippocampus. In contrast, VEGFR3 expression increased with development in the cortex in neurons and astrocytes, and appeared in the emerging population of oligodendroglial progenitors. High expression in ventricular ependyma, choroid plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was found in association with VEGFR3 throughout development, with highest expression in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3 signaling in neuronal proliferation in early forebrain development

  20. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  1. TROPICAL METEOROLOGY & Climate: Hadley Circulation

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jian; Vecchi, Gabriel A.

    2015-01-30

    The Hadley circulation, a prominent circulation feature characterized by rising air near the Equator and sinking air in the subtropics, defines the position of dry subtropical areas and is a fundamental regulator of the earth’s energy and momentum budgets. The character of the Hadley circulation, and its related precipitation regimes, exhibits variation and change in response to both climate variability and radiative forcing changes. The strength and position of the Hadley circulation change from year to year paced by El Niño and La Niña events. Over the last few decades of the twentieth century, the Hadley cell has expanded poleward in both hemispheres, with changes in atmospheric composition (including stratospheric ozone depletion and greenhouse gas increases) thought to have contributed to its expansion. This article introduces the basic phenomenology and driving mechanism of the Hadley circulation and discusses its variations under both natural and anthropogenic climate forcings.

  2. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  3. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings

    2012-01-01

    The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

  4. The Initial Investigation of Stimulating Fold Inguen Vascular Plexus by Medium Frequency Electric on Circulation of Proximate Inferior Extremity%中频电刺激腹股沟血管丛对下肢近端血液循环变化的初步探讨

    Institute of Scientific and Technical Information of China (English)

    马如梦; 马进; 李晓京; 王涛; 李烨; 文治洪; 胡文东

    2012-01-01

    Objective: To explore the effect of low intensity of medium frequency electric stimulating on fold inguen vascular plexus. Methods: 32 healthy men were randomly divided into two groups, which was defined the modulated medium frequency group and the control group. Before the test, we put the LDF probe and the thermal probe fixed on the subject at 5cm above the right knee medial; Put the modulated medium frequency electrodes on bilateral guinal vascular plexus. The control group also were placed modulated medium frequency electrode, but with no current output; The ECG electrodes were to put on the body in the limb lead way. Current perception was above the Sensory Thresholds, and the time of stimulation was 20 minutes. After the resting of 15 minutes, make the subjects maintain relaxed lying position and continuous monitoring the result for 30 minutes, the result was extracted every 5 minutes. The indices were skin blood flow, skin temperature and heart rate variability. Results: The results of the study indicate that, skin blood flow, skin temperature and LF were significantly changed with time interval. However, HF and LF/HF had not changed significantly. The modulated medium frequency group's indices greatly surpassed the control group's. Conclusion: The effect of MMFC group was better than the control group and the stimulation of fold inguen vascular plexus by suprathreshold intensity of medium frequency electric can improve distal lower limb skin blood flow obviously, which could prevent edema or anesthesia of lower limb.%目的:探讨中频电刺激股沟血管丛对下肢血液循环的影响.方法:32名健康男性随机分为2组,将LDF探头、热敏探头以双面胶固定在受试者右膝关节内侧上方5cm处,电流强度为感觉阈上.一组接受调制中频电刺激,另一组是对照组.刺激时间为20分钟,休息15分钟后,连续监测时间为30分钟,每5分钟为一个时间段,生理信号记录的是第一个5分钟、第三个5

  5. Lymph vessels: the forgotten second circulation in health and disease.

    Science.gov (United States)

    Adamczyk, Lukasz A; Gordon, Kristiana; Kholová, Ivana; Meijer-Jorna, Lorine B; Telinius, Niklas; Gallagher, Patrick J; van der Wal, Allard C; Baandrup, Ulrik

    2016-07-01

    The lymphatic circulation is still a somewhat forgotten part of the circulatory system. Despite this, novel insights in lymph angiogenesis in health and disease, application of immune markers for lymphatic growth and differentiation and also the introduction of new imaging techniques to visualize the lymphatic circulation have improved our understanding of lymphatic function in both health and disease, especially in the last decade. These achievements yield better understanding of the various manifestations of lymph oedemas and malformations, and also the patterns of lymphovascular spread of cancers. Immune markers that recognize lymphatic endothelium antigens, such as podoplanin, LYVE-1 and Prox-1, can be successfully applied in diagnostic pathology and have revealed (at least partial) lymphatic differentiation in many types of vascular lesions.

  6. Low matrix metalloproteinase levels precede vascular lesion formation in the JCR:LA-cp rat.

    Science.gov (United States)

    Wilson, David; Massaeli, Hamid; Russell, James C; Pierce, Grant N; Zahradka, Peter

    2003-07-01

    Clinically significant occlusive vascular lesions contain more extracellular matrix (ECM) proteins and lipid deposition than healthy vascular tissue. The events leading to this condition remain unresolved. One possibility is that ECM deposition may exceed ECM degradation which would contribute to the expansion of the vascular lesion. Utilizing lean (+/?) and insulin-resistant, corpulent (cp/cp) JCR:LA-cp rats, which are predisposed to develop vascular lesions, we have compared the matrix metalloproteinase (MMP) profile prior to the development of significant vascular lesions. Analysis of serum MMPs revealed that cp/cp rats have lower circulating levels than (+/?) controls. This is observed prior to the development of any noticeable atherosclerotic lesions. It also occurs as the hyperinsulinemia and insulin resistance is first developing in these rats. Female corpulent animals, which are less prone to develop vascular lesions, also exhibit a depressed serum MMP profile of a similar magnitude to their male counterparts. Primary vascular smooth muscle cells isolated from cp/cp animals also showed a reduction in secreted MMP compared with cells derived from +/? lean controls. We conclude that reduced MMP levels could lead to increased ECM accumulation and thus contribute to early vascular lesion formation.

  7. On Measuring the Metallicity of Supernovae Type Ia Progenitors

    CERN Document Server

    Miles, Broxton J; Townsley, Dean M; Timmes, F X; Jackson, Aaron P; Calder, Alan C; Brown, Edward F

    2015-01-01

    In Type Ia Supernovae (\\sneia), the relative abundances of chemical elements are affected by the neutron excess in the composition of the progenitor white dwarf. Since these products leave signatures in the spectra near maximum light, spectral features may be used to constrain the composition of the progenitor. We calculate the nucleosynthetic yields for three \\snia simulations for a wide range of progenitor metallicities, and calculate synthetic light curves and spectra to explore correlations between progenitor metallicity and the strength of spectral features. We use two 2D simulations of the deflagration-detonation-transition scenario with different $^{56}$Ni yields and the W7 simulation to control for differences between explosion models and total yields. While the overall yields of intermediate mass elements (16 $<$ A $\\leq$ 40) differ between the three cases, trends in the yields are similar. With increasing metallicity, $^{28}$Si yields remain nearly constant, $^{40}$Ca yields decline, and Ti and $...

  8. Senegenin promotes in vitro proliferation of human neural progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Fang Shi; Zhigang Liang; Zixuan Guo; Ran Li; Fen Yu; Zhanjun Zhang; Xuan Wang; Xiaomin Wang

    2011-01-01

    Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus.However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood.Cells from a ventral mesencephalon neural progenitor cell line (ReNcell VM) were utilized as models for pharmaceutical screening.The effects of various senegenin concentrations on cell proliferation were analyzed,demonstrating that high senegenin concentrations (5, 10, 50, and 100 pmo/L), particularly 50 pmol/L, significantly promoted proliferation of ReNcell VM cells.In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases.Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors.Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.

  9. Observational clues to the progenitors of Type-Ia supernovae

    CERN Document Server

    Maoz, Dan; Nelemans, Gijs

    2013-01-01

    Type-Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and endpoints of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a non-degenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of their sites, pre...

  10. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  11. Adipose-Derived Stem Cell-Seeded Hydrogels Increase Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds.

    Science.gov (United States)

    Kosaraju, Revanth; Rennert, Robert C; Maan, Zeshaan N; Duscher, Dominik; Barrera, Janos; Whittam, Alexander J; Januszyk, Michael; Rajadas, Jayakumar; Rodrigues, Melanie; Gurtner, Geoffrey C

    2016-02-01

    Adipose-derived mesenchymal stem cells (ASCs) are appealing for cell-based wound therapies because of their accessibility and ease of harvest, but their utility is limited by poor cell survival within the harsh wound microenvironment. In prior work, our laboratory has demonstrated that seeding ASCs within a soft pullulan-collagen hydrogel enhances ASC survival and improves wound healing. To more fully understand the mechanism of this therapy, we examined whether ASC-seeded hydrogels were able to modulate the recruitment and/or functionality of endogenous progenitor cells. Employing a parabiosis model and fluorescence-activated cell sorting analysis, we demonstrate that application of ASC-seeded hydrogels to wounds, when compared with injected ASCs or a noncell control, increased the recruitment of provascular circulating bone marrow-derived mesenchymal progenitor cells (BM-MPCs). BM-MPCs comprised 23.0% of recruited circulating progenitor cells in wounds treated with ASC-seeded hydrogels versus 8.4% and 2.1% in those treated with controls, p functional modulation of BM-MPCs, we demonstrate a statistically significant increase in BM-MPC migration, proliferation, and tubulization when exposed to hydrogel-seeded ASC-conditioned medium versus control ASC-conditioned medium (73.8% vs. 51.4% scratch assay closure; 9.1% vs. 1.4% proliferation rate; 10.2 vs. 5.5 tubules/HPF; p assays). BM-MPC expression of genes related to cell stemness and angiogenesis was also significantly increased following exposure to hydrogel-seeded ASC-conditioned medium (p functionality to effect greater neovascularization. PMID:26871860

  12. Vascular remodeling in the growth hormone transgenic mouse.

    Science.gov (United States)

    Dilley, R J; Schwartz, S M

    1989-11-01

    Using mice transgenic for the growth hormone gene (TGHM), we have studied the effects of a systemic elevation of growth hormone on vascular growth with the aim of investigating the role of vascular mass changes in producing hypertension. In contrast to human acromegaly or gigantism, there was no elevation of blood pressure in TGHM, but there were significant increases in vascular wall mass. In accordance with a presumably increased perfusion of larger organs, the medial cross-sectional areas of thoracic aorta and mesenteric resistance vessels were greater in the TGHM. These differences could be normalized in the aorta by body weight and in the mesenteric vessel by small intestine weight. Furthermore, the brain was not significantly heavier in the TGHM, and their carotid and cerebral vessels also were not larger. Wall-to-lumen ratios were similar in the aorta, carotid, and middle cerebral arteries suggesting that wall stress was the controlling factor in wall thickness. Surprisingly, the mesenteric vessels had increased wall-to-lumen ratio, which was similar to that seen in hypertensive vascular remodeling but in a normotensive animal. In an attempt to explain this finding it was noted that the pattern of mesenteric vascular networks and even organized structure within the vessel wall itself appeared to be fixed, perhaps by genetic mechanisms. Thus, vascular network structure may be a potentially limiting factor in the ability of the vessel wall to remodel and may have been responsible for the greater wall-to-lumen ratio in TGHM mesenteric vessels. A similar situation in human acromegaly or gigantism could result in a circulation marginally able to correct for other demands on blood flow resulting in about one third of cases being hypertensive. PMID:2805241

  13. Circulating Immune Complexes among Diabetic Children

    Directory of Open Access Journals (Sweden)

    George Nicoloff

    2004-01-01

    Full Text Available Insulin dependent diabetes mellitus (IDDM is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC. CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA. We studied the levels of CIC (IgG, IgM and IgA in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years, 29 of them had vascular complications (group 1 and the other 29 were without vascular complications (group 2. As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years. Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03 than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011 Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65% were positive for CIC IgG, 8/26 (31% for CIC IgM and 2/26 (8% for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005 and microalbuminuria (r=0.42, p=0.033. CIC IgA correlated with age (r=0.44, p=0.03. CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02. These

  14. Endothelial progenitors in sepsis: vox clamantis in deserto?

    OpenAIRE

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the ...

  15. Endometrial stem/progenitor cells: the first 10 years

    OpenAIRE

    Gargett, Caroline E; Schwab, Kjiana E.; Deane, James A

    2015-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstru...

  16. Human pancreatic islet progenitor cells demonstrate phenotypic plasticity in vitro

    Indian Academy of Sciences (India)

    Maithili P Dalvi; Malati R Umrani; Mugdha V Joglekar; Anandwardhan A Hardikar

    2009-10-01

    Phenotypic plasticity is a phenomenon that describes the occurrence of 2 or more distinct phenotypes under diverse conditions. This article discusses the work carried out over the past few years in understanding the potential of human pancreatic islet-derived progenitors for cell replacement therapy in diabetes. The phenotypic plasticity exhibited by pancreatic progenitors during reversible epithelial-to-mesenchymal transition (EMT) and possible role of microRNAs in regulation of this process is also presented herein.

  17. Osteocytes serve as a progenitor cell of osteosarcoma

    OpenAIRE

    Sottnik, Joseph L.; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L.; Keller, Evan T.

    2014-01-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. A...

  18. Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease

    OpenAIRE

    Leeman, Kristen T.; Fillmore, Christine M.; Kim, Carla F.

    2014-01-01

    The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of c...

  19. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    Science.gov (United States)

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  20. Trasplante de progenitores hemopoyéticos Transplant of hemopoietic progenitors

    Directory of Open Access Journals (Sweden)

    J. J. Rifón

    2006-08-01

    Full Text Available En la segunda mitad del siglo XX el trasplante de progenitores hemopoyéticos ha pasado de ser un tratamiento desesperado con una alta incidencia de complicaciones que implicaba una elevada mortalidad, a ser un tratamiento curativo para miles de pacientes con neoplasias hematológicas y otras enfermedades. Desde entonces se han ampliado los conocimientos sobre las células madre hemopoyéticas, la sangre periférica ha sustituido a la médula ósea como fuente de progenitores, la sangre de cordón se ha establecido como fuente viable de progenitores, la realización de trasplantes no emparentados es una realidad para muchos pacientes. La mejora en los regímenes de acondicionamiento y la introducción de los regímenes no mieloablativos han disminuido las recaídas. Las nuevas técnicas diagnósticas y los nuevos tratamientos antimicrobianos han disminuido las complicaciones infecciosas y su mortalidad. Se han desarrollado los conocimientos en determinación de enfermedad mínima residual y el efecto antitumoral de los linfocitos del donante lo que ha permitido ampliar las indicaciones. Además, los nuevos conocimientos en la inmunobiología del trasplante han mejorado por un lado las opciones de controlar una de las principales complicaciones como es la enfermedad injerto contra huésped, y por otro un mejor aprovechamiento del efecto inmunoterápico del trasplante.In the second half of the XX century, the transplant of hemopoietic progenitors ceased to be a desperate treatment with a high incidence of complications implying a high mortality, and became a curative treatment for thousands of patients with hematological neoplasias and other diseases. Since then understanding of the hemopoietic stem cells has increased, peripheral blood has replaced bone marrow as a source of progenitors, cord blood has been established as a viable source of progenitors and the realisation of unrelated transplants is a reality for many patients. The improvement of

  1. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Yu-Qing Li

    2016-06-01

    Full Text Available Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53 gene but absence of Cdkn1a (p21 did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

  2. Decreased microRNA is involved in the vascular remodeling abnormalities in chronic kidney disease (CKD.

    Directory of Open Access Journals (Sweden)

    Neal X Chen

    Full Text Available Patients with CKD have abnormal vascular remodeling that is a risk factor for cardiovascular disease. MicroRNAs (miRNAs control mRNA expression intracellularly and are secreted into the circulation; three miRNAs (miR-125b, miR-145 and miR-155 are known to alter vascular smooth muscle cell (VSMC proliferation and differentiation. We measured these vascular miRNAs in blood from 90 patients with CKD and found decreased circulating levels with progressive loss of eGFR by multivariate analyses. Expression of these vascular miRNAs miR-125b, miR-145, and miR-155 was decreased in the thoracic aorta in CKD rats compared to normal rats, with concordant changes in target genes of RUNX2, angiotensin II type I receptor (AT1R, and myocardin. Furthermore, the expression of miR-155 was negatively correlated with the quantity of calcification in the aorta, a process known to be preceded by vascular de-differentiation in these animals. We then examined the mechanisms of miRNA regulation in primary VSMC and found decreased expression of miR-125b, 145, and 155 in VSMC from rats with CKD compared to normal littermates but no alteration in DROSHA or DICER, indicating that the low levels of expression is not due to altered intracellular processing. Finally, overexpression of miR-155 in VSMC from CKD rats inhibited AT1R expression and decreased cellular proliferation supporting a direct effect of miR-155 on VSMC. In conclusion, we have found ex vivo and in vitro evidence for decreased expression of these vascular miRNA in CKD, suggesting that alterations in miRNAs may lead to the synthetic state of VSMC found in CKD. The decreased levels in the circulation may reflect decreased vascular release but more studies are needed to confirm this relationship.

  3. Constructal law of vascular trees for facilitation of flow.

    Directory of Open Access Journals (Sweden)

    Mohammad S Razavi

    Full Text Available Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures.

  4. Constructal law of vascular trees for facilitation of flow.

    Science.gov (United States)

    Razavi, Mohammad S; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S

    2014-01-01

    Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures. PMID:25551617

  5. Constructal Law of Vascular Trees for Facilitation of Flow

    Science.gov (United States)

    Razavi, Mohammad S.; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S.

    2014-01-01

    Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures. PMID:25551617

  6. Value of cerebral perfusion and vascular reserve for the treatment of symptomatic intracranial arterial stenosis

    Institute of Scientific and Technical Information of China (English)

    Li'an Huang; Xuewen Song; Anding Xu

    2008-01-01

    BACKGROUND: It is crucial to understand cerebral perfusion and vascular reserve in stegnotic arterial blood-supply regions to treat ischemic cerebrovascular diseases. However, effects on symptomatic intracrani-al arterial stenosis (SICAS) need to be further studied in additional applications. OBJECTIVE: To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. RETRIEVAL STRATEGY: A computer-based online search of English language publications from January 2000 to July 2007 was conducted in PubMed to identify publications that addressed cerebral perfusion and vascular reserve of SICAS. Search key words were "intracranial stenosis, perfusion, brain reserve". Relevant data were also searched with the China Journal Net, using the same key words in Chinese from January 2000 to January 2007. In total, 101 articles were retrieved. Inclusion criteria: ① Articles describing the current status for the diagnosis and treatment of SICAS; ② Articles concerning research developments of cerebral perfusion and vascular reserve of SICAS. Exclusion criteria: duplicated articles. LITERATURE EVALUATION: This study included 21 articles of experimental studies and conference re-ports.DATA SYNTHESIS: When performing interventional surgery in SICAS patients, it is important to under-stand cerebral perfusion and vascular reserve in addition to knowing the clinical symptoms and degrees of arterial stenosis. In recent years, there are a growing number of reports on measurements of vascular reserve through the use of magnetic resonance perfusion imaging (MR-PWI). Investigations demonstrate cerebral perfusion and vascular reserve decrease in many SICAS patients. Many studies show that both improve after surgical intervention. CONCLUSION: Cerebral perfusion could provide direct evidence of whether ischemia has occurred in the brain. Because of lateral circulation and cerebral vascular reserve, intracranial vascular stenosis and/or decreased

  7. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

    OpenAIRE

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Benjamin T Suratt; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-01-01

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese m...

  8. Boosting Hematopoietic Engraftment after in Utero Transplantation through Vascular Niche Manipulation.

    Science.gov (United States)

    Mokhtari, Saloomeh; Colletti, Evan J; Atala, Anthony; Zanjani, Esmail D; Porada, Christopher D; Almeida-Porada, Graça

    2016-06-14

    In utero hematopoietic stem/progenitor cell transplantation (IUHSCT) has only been fully successful in the treatment of congenital immunodeficiency diseases. Using sheep as a large animal model of IUHSCT, we demonstrate that administration of CD146(+)CXCL12(+)VEGFR2(+) or CD146(+)CXCL12(+)VEGFR2(-) cells prior to, or in combination with, hematopoietic stem/progenitor cells (HSC), results in robust CXCL12 production within the fetal marrow environment, and significantly increases the levels of hematopoietic engraftment. While in the fetal recipient, donor-derived HSC were found to reside within the trabecular bone, the increased expression of VEGFR2 in the microvasculature of CD146(+)CXCL12(+)VEGFR2(+) transplanted animals enhanced levels of donor-derived hematopoietic cells in circulation. These studies provide important insights into IUHSCT biology, and demonstrate the feasibility of enhancing HSC engraftment to levels that would likely be therapeutic in many candidate diseases for IUHSCT. PMID:27304918

  9. Possible Progenitor of Special Supernova Type Detected

    Science.gov (United States)

    2008-04-01

    caused by material being pulled off a companion star onto the white dwarf, fusion of this material on the surface of the star should heat the star and produce a strong source of X-radiation prior to the explosion. Once the supernova explosion occurs, the white dwarf is expected to be completely destroyed and then would be undetectable in X-rays. In the merger scenario, the intensity of X-ray emission prior to the explosion is expected to be much weaker. Based on the detection of a fairly strong X-ray source at approximately the position of SN 2007on 4 years before the explosion, Voss and Nelemans conclude that the data support the scenario where matter is pulled off a companion star. The small number of X-ray sources in the field implies that there is only a small chance of an unrelated source being so close by coincidence. Also, the X-ray source has similar properties to those expected for fusion on a white dwarf, unlike most X-ray sources in the sky. However, in follow-up studies, Voss, Nelemans and colleagues Gijs Roelofs (Harvard-Smithsonian Center for Astrophysics, Cambridge, Mass.) and Cees Bassa (McGill University, Canada) used higher-quality optical images to better determine the supernova's position. This work, which is not yet published, shows a small, but significant difference in the measured positions of the supernova and the X-ray source, suggesting the source may not be the progenitor. Follow-up Chandra observations hint that the X-ray object has disappeared, but further observations are needed to finally decide whether the source was the progenitor or not. The team is also applying this new method to other supernovas and has high hopes that they will eventually succeed in identifying the elusive cause of at least some of these explosions. "We're very excited about opening up a new way of studying supernovas, even though we're not sure that we've seen this particular stellar bomb before it exploded," said Gijs Roelofs. "We're very confident that we

  10. Binary progenitor models of type IIb supernovae

    CERN Document Server

    Claeys, J S W; Pols, O R; Eldridge, J J; Baes, M

    2011-01-01

    Massive stars that lose their hydrogen-rich envelope down to a few tenths of a solar mass explode as extended type IIb supernovae, an intriguing subtype that links the hydrogen-rich type II supernovae with the hydrogen-poor type Ib and Ic. The progenitors may be very massive single stars that lose their envelope due to their stellar wind, but mass stripping due to interaction with a companion star in a binary system is currently considered to be the dominant formation channel. We computed an extensive grid of binary models with the Eggleton binary evolution code. The predicted rate from our standard models, which assume conservative mass transfer, is about 6 times smaller than the current rate indicated by observations. It is larger but still comparable to the rate expected from single stars. To recover the observed rate we must generously allow for uncertainties and low accretion efficiencies in combination with limited angular momentum loss from the system. Motivated by the claims of detection and non-detec...

  11. The Evolution of Relativistic Binary Progenitor Systems

    CERN Document Server

    Francischelli, G J; Brown, G E

    2001-01-01

    Relativistic binary pulsars, such as B1534+12 and B1913+16 are characterized by having close orbits with a binary separation of ~ 3 R_\\sun. The progenitor of such a system is a neutron star, helium star binary. The helium star, with a strong stellar wind, is able to spin up its compact companion via accretion. The neutron star's magnetic field is then lowered to observed values of about 10^{10} Gauss. As the pulsar lifetime is inversely proportional to its magnetic field, the possibility of observing such a system is, thus, enhanced by this type of evolution. We will show that a nascent (Crab-like) pulsar in such a system can, through accretion-braking torques (i.e. the "propeller effect") and wind-induced spin-up rates, reach equilibrium periods that are close to observed values. Such processes occur within the relatively short helium star lifetimes. Additionally, we find that the final outcome of such evolutionary scenarios depends strongly on initial parameters, particularly the initial binary separation a...

  12. Subretinal transplantation of mouse retinal progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Caihui Jiang; Maonian Zhang; Henry Klassen; Michael Young

    2011-01-01

    The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells (RPCs) were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.

  13. Type Ia Supernovae: Colors, Rates, and Progenitors

    CERN Document Server

    Heringer, Epson; Kezwer, Jason; Graham, Melissa L; Sand, David; Bildfell, Chris

    2016-01-01

    The rate of type Ia supernovae (SNe Ia) in a galaxy depends not only on stellar mass, but also on star formation history. Here we show that two simple observational quantities ($g-r$ or $u-r$ host galaxy color, and $r$-band luminosity), coupled with an assumed delay time distribution (the rate of SNe Ia as a function of time for an instantaneous burst of star formation), are sufficient to accurately determine a galaxy's SN Ia rate, with very little sensitivity to the precise details of the star formation history. Using this result, we compare observed and predicted color distributions of SN Ia hosts for the MENeaCS cluster supernova survey, and for the SDSS Stripe 82 supernova survey. The observations are consistent with a continuous delay time distribution (DTD), without any cutoff. For old progenitor systems the power-law slope for the DTD is found to be $-1.50 ^{+0.19} _{-0.15}$. This result favours the double degenerate scenario for SN Ia, though other interpretations are possible. We find that the late-t...

  14. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  15. [The future of vascular medicine].

    Science.gov (United States)

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step.

  16. Endothelial progenitor cell transplantation ameliorates elastin breakdown in a Kawasaki disease mouse model

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhi; DU Zhong-dong; LIU Jun-feng; LU Dun-xiang; LI Li; GUAN Yun-qian; WAN Sui-gui

    2012-01-01

    Background Coronary artery damage from Kawasaki disease (KD) is closely linked to the dysfunction of endothelial progenitor cells (EPCs).The aim of the present study was to evaluate the therapeutic effect of EPCs transplantation in KD model.Methods Lactobacillus casei cell wall extract (LCWE)-induced KD model in C57BL/6 mice was established.The model mice were injected intravenously with bone marrow-derived in vitro expanded EPCs.Histological evaluation,number of circulating EPCs and the function of bone marrow EPCs were examined at day 56.Results Inflammation was found around the coronary artery of the model mice after 14 days,Elastin breakdown was observed after 56 days.CM-Dil labeled EPCs incorporated into vessel repairing foci was found.At day 56,the number of peripheral EPCs in the KD model group was lower than in EPCs transplanted and control group.The functional index of bone marrow EPCs from the KD model group decreased in proliferation,adhesion and migration.Increased number of circulating EPCs and improved function were observed on the EPCs transplanted group compared with model group.Conclusion Exogenously administered EPCs,which represent a novel strategy could prevent the dysfunction of EPCs,accelerate the repair of coronary artery endothelium lesion and decrease the occurrence of aneurysm.

  17. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization.

    Science.gov (United States)

    Sun, Jiayin; Xie, Jun; Kang, Lina; Ferro, Albert; Dong, Li; Xu, Biao

    2016-01-01

    Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg(-1) day(-1)), amlodipine (2.5 mgkg(-1) day(-1)), or vehicle by gavage (n = 20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this. PMID:27243031

  18. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

    Directory of Open Access Journals (Sweden)

    Jiayin Sun

    2016-01-01

    Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

  19. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

    Energy Technology Data Exchange (ETDEWEB)

    Baer, Caroline; Squadrito, Mario Leonardo [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Iruela-Arispe, M. Luisa, E-mail: arispe@mcdb.ucla.edu [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles 90095, CA (United States); De Palma, Michele, E-mail: michele.depalma@epfl.ch [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland)

    2013-07-01

    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches.

  20. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

    International Nuclear Information System (INIS)

    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches

  1. Effect of Weight Reduction on Cardiovascular Risk Factors and CD34-positive Cells in Circulation

    Directory of Open Access Journals (Sweden)

    Nina A Mikirova, Joseph J Casciari, Ronald E Hunninghake, Margaret M Beezley

    2011-01-01

    Full Text Available Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis.In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs on the body composition, lipid profile and CD34-positive cells in circulation.During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting.The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers.As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation.

  2. The circulation physiology of agroecosystems

    Institute of Scientific and Technical Information of China (English)

    Cao Zhiping; Richard Dawson

    2007-01-01

    This paper represents an effort to enlarge the understanding of the biophysical foundation of agroecosystems by using an analogy with the circulation of the blood in the human body. The circulation function in the human body can be represented as arterial pressure. The factors affecting arterial pressure in the human body have direct counterparts in the cultivation-husbandry system. The relationship between circulation pressure and the factors affecting that pressure in the cultivation-husbandry system are similar to the relationship between the arterial pressure and factors affecting arterial pressure in the human body. Furthermore, circulation resistance in the cultivation-husbandry system can be shown to be analogous to the calculation of peripheral resistance in the human body by Poiseuille's formula.

  3. [Retinal vascular changes--predictive and prognostic factor in systemic disease].

    Science.gov (United States)

    Vicol, Anca Delia; Bogdănici, Tudor; Bogdănici, Camelia

    2014-01-01

    The retinal circulation represents a unique window for the direct, non invazive in vivo status of the systemic mycrocirculation, but it can also offer scientific support for theories related strictly to ocular diseases, such as glaucoma (vascular theory). The interaction between intraocular pressure, retinal vessels and cerebrospinal fluid pressure located at the retrolaminar part of the optic nerve has been of great interest for both ophthalmologists or neuroscientists, both clinicians and researchers. The retinal vascular bed has structural and functional similarities with other vascular teritories such as Central Nervous System (CNS), kidneys and heart, so as for the ophthalmologist any vascular change in the retina can signalize a systemic disease (diabetes mellitus, stroke, arterial hypertension) that is more or less symptomatic for the patient. The purpose of this meta-analysis was to reviview recent literature data related to the connections between different hemodynamic structures and their impact on the retinal blood flow.

  4. Atmospheric Circulation of Terrestrial Exoplanets

    OpenAIRE

    Showman, Adam P.; Wordsworth, Robin D.; Merlis, Timothy M.; Kaspi, Yohai

    2013-01-01

    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical a...

  5. Flow Cytometric Identification of Fibrocytes in the Human Circulation.

    Science.gov (United States)

    Hu, Xinyuan; DeBiasi, Erin M; Herzog, Erica L

    2015-01-01

    Because the incidence of organ fibrosis increases with age, various fibrosing disorders are projected to account for significant increases in morbidity, mortality, and healthcare costs in the years to come. Treatments for these diseases are scarce and better understanding of the immunopathogenesis of fibrosis and its relationship to aging are sorely needed. One area of interest in this field is the role that fibrocytes might play in the development of tissue remodeling and fibrosis. Fibrocytes are mesenchymal progenitor cells presumed to be of monocyte origin that possess the tissue remodeling properties of tissue resident fibroblasts such as extracellular matrix production and α-SMA-related contractile properties, as well as the immunologic functions typically attributed to macrophages including production of cytokines and chemokines, antigen presentation, regulation of leukocyte trafficking, and modulation of angiogenesis. Fibrocytes could participate in the development of age-related fibrosing disorders through any or all of these functions. This chapter presents methods that have been developed for the study of circulating human fibrocytes. Protocols for the quantification of fibrocytes in the human circulation will be presented along with discussion of the technical challenges that are frequently encountered in this field. It is hoped that this information will facilitate further investigation of the relationship between fibrocytes, aging, and fibrosis, and perhaps uncover new areas of study in these difficult-to-treat and deadly diseases. PMID:26420706

  6. BK Channels in the Vascular System.

    Science.gov (United States)

    Krishnamoorthy-Natarajan, G; Koide, M

    2016-01-01

    Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the β1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or β1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators. PMID:27238270

  7. Circulating CXCL16 in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Usama Elewa

    2016-09-01

    Full Text Available Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013. In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.

  8. Vascular graft infections with Mycoplasma

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Skov Jensen, J; Prag, J;

    1995-01-01

    Vascular graft infection is one of the most serious complications in vascular surgery. It is associated with mortality rates ranging from 25% to 75% and with morbidity in the form of amputation in approximately 30% of patients. Staphylococcus aureus is the leading pathogen. With conventional...... laboratory techniques, the percentage of culture-negative yet grossly infected vascular grafts seems to be increasing and is not adequately explained by the prior use of antibiotics. We have recently reported the first case of aortic graft infection with Mycoplasma. We therefore suggest the hypothesis...... that the large number of culture-negative yet grossly infected vascular grafts may be due to Mycoplasma infection not detected with conventional laboratory technique....

  9. Zfp423 promotes adipogenic differentiation of bovine stromal vascular cells.

    Directory of Open Access Journals (Sweden)

    Yan Huang

    Full Text Available Intramuscular fat or marbling is critical for the palatability of beef. In mice, very recent studies show that adipocytes and fibroblasts share a common pool of progenitor cells, with Zinc finger protein 423 (Zfp423 as a key initiator of adipogenic differentiation. To evaluate the role of Zfp423 in intramuscular adipogenesis and marbling in beef cattle, we sampled beef muscle for separation of stromal vascular cells. These cells were immortalized with pCI neo-hEST2 and individual clones were selected by G418. A total of 288 clones (3×96 well plates were isolated and induced to adipogenesis. The presence of adipocytes was assessed by Oil-Red-O staining. Three clones with high and low adipogenic potential respectively were selected for further analyses. In addition, fibro/adipogenic progenitor cells were selected using a surface marker, platelet derived growth factor receptor (PDGFR α. The expression of Zfp423 was much higher (307.4±61.9%, P<0.05 in high adipogenic cells, while transforming growth factor (TGF-β was higher (156.1±48.7%, P<0.05 in low adipogenic cells. Following adipogenic differentiation, the expression of peroxisome proliferator-activated receptor γ (PPARγ and CCAAT/enhancer binding protein α (C/EBPα were much higher (239.4±84.1% and 310.7±138.4%, respectively, P<0.05 in high adipogenic cells. Over-expression of Zfp423 in stromal vascular cells and cloned low adipogenic cells dramatically increased their adipogenic differentiation, accompanied with the inhibition of TGF-β expression. Zfp423 knockdown by shRNA in high adipogenic cells largely prevented their adipogenic differentiation. The differential regulation of Zfp423 and TGF-β between low and high adipogenic cells is associated with the DNA methylation in their promoters. In conclusion, data show that Zfp423 is a critical regulator of adipogenesis in stromal vascular cells of bovine muscle, and Zfp423 may provide a molecular target for enhancing intramuscular

  10. Vascular contributions to cognitive impairment

    OpenAIRE

    Wright, Clinton B.; Flores, Alan

    2015-01-01

    Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible...

  11. The relationships of vascular plants.

    OpenAIRE

    Kenrick, P

    2000-01-01

    Recent phylogenetic research indicates that vascular plants evolved from bryophyte-like ancestors and that this involved extensive modifications to the life cycle. These conclusions are supported by a range of systematic data, including gene sequences, as well as evidence from comparative morphology and the fossil record. Within vascular plants, there is compelling evidence for two major clades, which have been termed lycophytes (clubmosses) and euphyllophytes (seed plants, ferns, horsetails)...

  12. Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development.

    Science.gov (United States)

    Chouinard-Pelletier, Guillaume; Jahnsen, Espen D; Jones, Elizabeth A V

    2013-01-01

    Vascular development is believed to occur first by vasculogenesis followed by angiogenesis. Though angiogenesis is the formation of new vessels, we found that vascular density actually decreases during this second stage. The onset of the decrease coincided with the entry of erythroblasts into circulation. We therefore measured the level of shear stress at various developmental stages and found that it was inversely proportional to vascular density. To investigate whether shear stress was inhibitory to angiogenesis, we altered shear stress levels either by preventing erythroblasts from entering circulation ("low" shear stress) or by injection of a starch solution to increase the blood plasma viscosity ("high" shear stress). By time-lapse microscopy, we show that reverse intussusception (merging of two vessels) is inversely proportional to the level of shear stress. We also found that angiogenesis (both sprouting and splitting) was inversely proportional to shear stress levels. These effects were specific to the arterial or venous plexus however, such that the effect on reverse intussusception was present only in the arterial plexus and the effect on sprouting only in the venous plexus. We cultured embryos under altered shear stress in the presence of either DAPT, a Notch inhibitor, or DMH1, an inhibitor of the bone morphogenetic protein (BMP) pathway. DAPT treatment phenocopied the inhibition of erythroblast circulation ("low" shear stress) and the effect of DAPT treatment could be partially rescued by injection of starch. Inhibition of the BMP signaling prevented the reduction in vascular density that was observed when starch was injected to increase shear stress levels.

  13. Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart

    Directory of Open Access Journals (Sweden)

    Dinender Singla

    2016-01-01

    Full Text Available We hypothesized that fibroblast growth factor-9 (FGF-9 would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p<0.05. Additionally, the number of c-kit+ve/SM α-actin+ve cells and c-kit+ve/CD31+ve cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p<0.05. Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p<0.05. Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p<0.05. Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.

  14. Multimodality imaging of vascular anomalies.

    Science.gov (United States)

    Restrepo, Ricardo

    2013-03-01

    Vascular malformations and hemangiomas are common in children but remain a source of confusion during diagnosis, in part because of the lack of a uniform terminology. With the existing treatments for hemangiomas and vascular malformations, it is important to make the correct diagnosis initially to prevent adverse physical and emotional sequelae in not only the child but also the family. The diagnosis of vascular malformations is made primarily by the clinician and based on the physical exam. Imaging is carried out using predominantly ultrasound (US) and magnetic resonance imaging (MRI), which are complementary modalities. In most cases of vascular anomalies, US is the first line of imaging as it is readily available, less expensive, lacks ionizing radiation and does not require sedation. MRI is also of great help for further characterizing the lesions. Conventional arteriography is reserved for cases that require therapeutic intervention, more commonly for arteriovenous malformations. Radiographs usually play no role in diagnosing vascular anomalies in children. In this article, the author describes the terminology and types of hemangiomas and vascular malformations and their clinical, histological features, as well as the imaging approach and appearance.

  15. Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.

    Science.gov (United States)

    Veas, Carlos; Jara, Casandra; Willis, Naomi D; Pérez-Contreras, Karen; Gutierrez, Nicolas; Toledo, Jorge; Fernandez, Paulina; Radojkovic, Claudia; Zuñiga, Felipe A; Escudero, Carlos; Aguayo, Claudio

    2016-04-01

    Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis.

  16. Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.

    Directory of Open Access Journals (Sweden)

    Francisco R Saenz

    Full Text Available Mammary epithelial (ME cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV-Neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+, and ESA+ (EpCam. These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

  17. Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Claudia O Rodrigues

    Full Text Available RATIONALE: The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types. OBJECTIVE: To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations. METHODS AND RESULTS: c-kit+, sca-1+ CPCs obtained from adult mouse left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and were self-renewing, pluripotent and clonogenic. Detailed single cell clonal analysis of 17 clones revealed that most (14/17 exhibited trilineage differentiation potential. However, striking morphological differences were observed among clones that were heritable and stable in long-term culture. 3 major groups were identified: round (7/17, flat or spindle-shaped (5/17 and stellate (5/17. Stellate morphology was predictive of vasculogenic differentiation in Matrigel. Genome-wide expression studies and bioinformatic analysis revealed clonally stable, heritable differences in stromal cell-derived factor-1 (SDF-1 expression that correlated strongly with stellate morphology and vasculogenic capacity. Endogenous SDF-1 production contributed directly to vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100, an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4, reduced tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non-vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel dermal implants in vivo, while CPCs with low SDF-1 production were not. CONCLUSIONS: Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene expression patterns and differentiation potential. Clone-specific levels of SDF-1 expression both predict and promote development of a vasculogenic phenotype via a previously unreported autocrine

  18. Chief sources of brachiopod recovery from the end Ordovician mass extinction with special references to progenitors

    Institute of Scientific and Technical Information of China (English)

    戎嘉余; 詹仁斌

    1999-01-01

    Survivor, Lazarus and progenitor taxa are sources of biotic recovery following mass extinction. Investigations of the benthic brachiopods through the latest Ordovician mass extinction shows that progenitors developed many evolutionary novelties and successful surviving mechanisms. They are superior to survivors and Lazarus taxa in their ability to adapt to environmental changes. They are the primary source of macroevolution and the ancestors of a number of new taxa. Three kinds of progenitors are recognized based on the Ordovician-Silurian brachiopods from South China: survivor-progenitors, crisis-progenitors and Lazarus-progenitors; the last has the strongest ability to resist adverse environments, and is the most diverse and abundant.

  19. On the Progenitor of the Type IIb Supernova 2016gkg

    CERN Document Server

    Kilpatrick, Charles D; Abramson, Louis E; Pan, Yen-Chen; Lu, Cicero-Xinyu; Williams, Peter; Treu, Tommaso; Siebert, Matthew R; Fassnacht, Christopher D; Max, Claire E

    2016-01-01

    We present a detection in pre-explosion Hubble Space Telescope (HST) imaging of a point source consistent with being the progenitor star of the Type IIb supernova (SN IIb) 2016gkg. Post-explosion imaging from the Keck Adaptive Optics system was used to perform relative astrometry between the Keck and HST imaging. We identify a single point source in the HST images coincident with the SN position to 0.89-sigma. The HST photometry is consistent with the progenitor star being an A0Ia star with T=9500 K and log (L/Lsun)=5.15. We find that the SN 2016gkg progenitor star appears more consistent with binary than single-star evolutionary models. In addition, early-time light curve data from SN 2016gkg revealed a rapid rise in luminosity within ~0.4 days of non-detection limits, consistent with models of the cooling phase after shock break-out. We use these data to determine an explosion date of 20.15 September 2016 and progenitor star radius of log (R/Rsun)=2.41, which agrees with photometry from the progenitor star....

  20. Impaired DNA replication within progenitor cell pools promotes leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Ganna Bilousova

    2005-12-01

    Full Text Available Impaired cell cycle progression can be paradoxically associated with increased rates of malignancies. Using retroviral transduction of bone marrow progenitors followed by transplantation into mice, we demonstrate that inhibition of hematopoietic progenitor cell proliferation impairs competition, promoting the expansion of progenitors that acquire oncogenic mutations which restore cell cycle progression. Conditions that impair DNA replication dramatically enhance the proliferative advantage provided by the expression of Bcr-Abl or mutant p53, which provide no apparent competitive advantage under conditions of healthy replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in contexts of impaired DNA replication dramatically increases leukemogenesis. Impaired replication within hematopoietic progenitor cell pools can select for oncogenic events and thereby promote leukemia, demonstrating the importance of replicative competence in the prevention of tumorigenesis. The demonstration that replication-impaired, poorly competitive progenitor cell pools can promote tumorigenesis provides a new rationale for links between tumorigenesis and common human conditions of impaired DNA replication such as dietary folate deficiency, chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important for DNA metabolism.

  1. Observational Clues to the Progenitors of Type Ia Supernovae

    Science.gov (United States)

    Maoz, Dan; Mannucci, Filippo; Nelemans, Gijs

    2014-08-01

    Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites—pre- and postexplosion—from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress.

  2. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  3. Color Doppler in the Assessment of Uteroplacental Circulation Insufficiency

    Directory of Open Access Journals (Sweden)

    Ahmad Soltani Shirazi

    2010-05-01

    Full Text Available Usage of color Doppler ultrasound in the diagnosis of uteroplacental or fetal-placental vascular insufficiency is based on the theory that many of these insufficiencies are due to small vessel disease in the uteroplacental or fetal-placental vasculature which ultimately results in fetal intrauterine growth retardation, increase in prenatal mortality and morbidity and fetal neurological development. "nIn a prospective study on patients who were sus-pected for developing uteroplacental insufficiency, color Doppler ultrasound was done and the results were compared with neonatal weight (one of the most important criteria for IUGR determination which was measured just after delivery."nDirect significant relation was showed to be present between prepartum vascular changes detected in Doppler ultrasound and prognosis of IUGR. "nThree vessel types were assessed in this study:"n1. Umbilical-middle cerebral arteries"n2. Uterine arteries"n3.Venous system (umbilical, ductus venosus, IVC, which is used to assess the compensation process in fetal circulation."nThree Doppler indices of vascular resistance were studied and their abnormalities according to the age of pregnancy were assessed.

  4. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  5. p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

    Directory of Open Access Journals (Sweden)

    Kyung Hee Chang

    2014-12-01

    Full Text Available In the bone marrow (BM, hematopoietic progenitors (HPs reside in specific anatomical niches near osteoblasts (Obs, macrophages (MΦs, and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling. Consequently, Ob p62-deficient mice lose bone, Ob Ccl4 expression, and HP chemotaxis toward Cxcl12, resulting in egress of short-term hematopoietic stem cells and myeloid progenitors. Finally, Ccl4 expression and myeloid progenitor egress are reversed by deficiency of the p62 PB1-binding partner Nbr1. A functional “MΦ-Ob niche” is required for myeloid progenitor/short-term stem cell retention, in which Ob p62 is required to maintain NF-κB signaling repression, osteogenesis, and BM progenitor retention.

  6. Does liver-intestine significantly degrade circulating endogenous substance P in man?

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B

    1986-01-01

    was determined in various vascular beds during a right-sided catheterization in 13 subjects without liver insufficiency. All subjects had normal values of circulating substance P, and no significant difference was found between systemic plasma and hepatic venous or renal venous concentrations of substance P......Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P...

  7. Obesity in Indian subjects with Vascular Dementia

    OpenAIRE

    CHANDRA, Mina; Anand, Kuljeet Singh Anand

    2015-01-01

    ABSTRACT Background: Obesity is considered a public health challenge in South Asia. Obesity is an independent risk factor in vascular dementia. It also contributes to other risk factors of vascular dementia like hypertension, coronary artery disease, dyslipidaemia and diabetes. As the rate of obesity in Indian subjects with vascular dementia is not known, we decided to assess obesity in subjects with vascular dementia. Methods: Subjects with vascular dementia presenting to Mem...

  8. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury.

    Science.gov (United States)

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-09-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5(+) (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5(+) cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in

  9. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  10. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael

    2004-08-16

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z {approx} 0.01-0.1 of r{sub V} = 4.26{sub -1.93 -0.10}{sup +1.39 +0.10} h{sup 3} x 10{sup -4} SNe Ia/yr/Mpc{sup 3} from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  11. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of rV = 4.26-1.93-0.10+1.39+0.10 h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  12. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  13. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

    DEFF Research Database (Denmark)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel;

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature...

  14. CXCR4 expression in prostate cancer progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Dubrovska

    Full Text Available Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+/CD133(+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.

  15. A neutron star progenitor for FRBs? Insights from polarisation measurements

    CERN Document Server

    Ravi, Vikram

    2016-01-01

    Fast Radio Bursts (FRBs) are intense, millisecond-duration broadband radio transients, the emission mechanisms of which are not understood. Masui et al. recently presented Green Bank Telescope observations of FRB 110523, which displayed temporal variation of the linear polarisation position angle (PA). This effect is commonly seen in radio pulsars and is attributed to a changing projected magnetic field orientation in the emission region as the star rotates. If a neutron star is the progenitor of this FRB, and the emission mechanism is pulsar-like, we show that the progenitor is either rapidly rotating, or the emission originates from a region of complex magnetic field geometry. The observed PA variation could also be caused by propagation effects within a neutron-star magnetosphere, or by spatially varying magnetic fields if the progenitor lies in a dense, highly magnetised environment. Although we urge caution in generalising results from FRB 110523 to the broader FRB population, our analysis serves as a gu...

  16. Osteocytes serve as a progenitor cell of osteosarcoma.

    Science.gov (United States)

    Sottnik, Joseph L; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L; Keller, Evan T

    2014-08-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, a SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. PMID:24700678

  17. Gravitational Wave Constraints on the Progenitors of Fast Radio Bursts

    CERN Document Server

    Callister, Thomas; Weinstein, Alan

    2016-01-01

    The nature of fast radio bursts (FRBs) remains enigmatic. Highly energetic radio pulses of millisecond duration, fast radio bursts are observed with dispersion measures consistent with an extragalactic source. A variety of models have been proposed to explain their origin. One popular class of theorized FRB progenitor is the coalescence of compact binaries composed of neutron stars and/or black holes. We demonstrate that measurements made by the LIGO and Virgo gravitational wave observatories can be leveraged to severely constrain the validity of FRB binary coalescence models. Existing measurements rule out binary black holes as FRB progenitors, and results from Advanced LIGO's O1 and O2 observing runs will either confirm or strongly rule out binary neutron star and neutron star-black hole progenitors.

  18. Immortalized neural progenitor cells for CNS gene transfer and repair.

    Science.gov (United States)

    Martínez-Serrano, A; Björklund, A

    1997-11-01

    Immortalized multipotent neural stem and progenitor cells have emerged as a highly convenient source of tissue for genetic manipulation and ex vivo gene transfer to the CNS. Recent studies show that these cells, which can be maintained and genetically transduced as cell lines in culture, can survive, integrate and differentiate into both neurons and glia after transplantation to the intact or damaged brain. Progenitors engineered to secrete trophic factors, or to produce neurotransmitter-related or metabolic enzymes can be made to repopulate diseased or injured brain areas, thus providing a new potential therapeutic tool for the blockade of neurodegenerative processes and reversal of behavioural deficits in animal models of neurodegenerative diseases. With further technical improvements, the use of immortalized neural progenitors may bring us closer to the challenging goal of targeted and effective CNS repair.

  19. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  20. Vascular neuroeffector activity in the rat during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Hart, J.L.; Freas, W.; Muldoon, S.M.

    1986-03-01

    The activity of the vascular neuroeffector junction was examined in pregnant (PG) and non-pregnant (NPG) rats to determine if changes could account for the reported alterations in sympathetic control of the maternal circulation. Caudal and mesenteric arteries were removed from NPG and 19-21PG rats and prepared for isometric tension recording in Krebs-filled, 37/sup 0/C tissue baths. At optimal passive tension frequency-response measurements were obtained with and without cocaine (10-/sup 5/M), followed by norepinephrine (NE) and tyramine conc-response measurements. The densely innervated caudal artery developed more tension in response to NE, tyramine and transmural electrical stimulation than did the moderately innervated mesenteric artery. There were no significant differences in responses between vessels from NPG and PG rats, NE content, /sup 3/H-NE accumulation, and effects of plasma on /sup 3/H-NE accumulation of NPG and PG caudal arteries were also compared. The NE content of the NPG artery (8.61 +/- .61) was not different from that of the PG artery (9.97 +/- .71 ..mu..g/g). Also, NE accumulation was similar, and plasma inhibited /sup 3/H-NE accumulation to the same extent. These results indicate that vascular neuroeffector functions of NE release, receptor sensitivity and uptake are not modified in the rat during pregnancy. Changes in sympathetic control of the circulation previously reported, therefore, are likely to be dependent on alterations at sites other than the neuroeffector junction.

  1. [Circulating nucleic acids and infertility].

    Science.gov (United States)

    Scalici, E; Mullet, T; Ferrières Hoa, A; Gala, A; Loup, V; Anahory, T; Belloc, S; Hamamah, S

    2015-09-01

    Circulating nucleic acids (cell-free DNA and microRNAs) have for particularity to be easily detectable in the biological fluids of the body. Therefore, they constitute biomarkers of interest in female and male infertility care. Indeed, in female, they can be used to detect ovarian reserve disorders (polycystic ovary syndrome and low functional ovarian reserve) as well as to assess follicular microenvironment quality. Moreover, in men, their expression levels can vary in case of spermatogenesis abnormalities. Finally, circulating nucleic acids have also the ability to predict successfully the quality of in vitro embryo development. Their multiple contributions during assisted reproductive technology (ART) make of them biomarkers of interest, for the development of new diagnostic and/or prognostic tests, applied to our specialty. Circulating nucleic acids would so offer the possibility of personalized medical care for infertile couples in ART. PMID:26298813

  2. Atmospheric Circulation of Terrestrial Exoplanets

    CERN Document Server

    Showman, Adam P; Merlis, Timothy M; Kaspi, Yohai

    2013-01-01

    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical and dynamical conditions, only a small fraction of which have yet been explored in detail. Our approach is to lay out the fundamental dynamical principles governing the atmospheric circulation on terrestrial planets--broadly defined--and show how they can provide a foundation for understanding the atmospheric behavior of these worlds. We first survey basic atmospheric dynamics, including the role of geostrophy, baroclinic instabilities, and jets in the strongly rotating regime (the "extratropics") and the role of the Hadle...

  3. Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage.

    Science.gov (United States)

    Woolthuis, Carolien M; Park, Christopher Y

    2016-03-10

    The classical model of hematopoiesis has long held that hematopoietic stem cells (HSCs) sit at the apex of a developmental hierarchy in which HSCs undergo long-term self-renewal while giving rise to cells of all the blood lineages. In this model, self-renewing HSCs progressively lose the capacity for self-renewal as they transit into short-term self-renewing and multipotent progenitor states, with the first major lineage commitment occurring in multipotent progenitors, thus giving rise to progenitors that initiate the myeloid and lymphoid branches of hematopoiesis. Subsequently, within the myeloid lineage, bipotent megakaryocyte-erythrocyte and granulocyte-macrophage progenitors give rise to unipotent progenitors that ultimately give rise to all mature progeny. However, over the past several years, this developmental scheme has been challenged, with the origin of megakaryocyte precursors being one of the most debated subjects. Recent studies have suggested that megakaryocytes can be generated from multiple pathways and that some differentiation pathways do not require transit through a requisite multipotent or bipotent megakaryocyte-erythrocyte progenitor stage. Indeed, some investigators have argued that HSCs contain a subset of cells with biased megakaryocyte potential, with megakaryocytes directly arising from HSCs under steady-state and stress conditions. In this review, we discuss the evidence supporting these nonclassical megakaryocytic differentiation pathways and consider their relative strengths and weaknesses as well as the technical limitations and potential pitfalls in interpreting these studies. Ultimately, such pitfalls will need to be overcome to provide a comprehensive and definitive understanding of megakaryopoiesis. PMID:26787736

  4. Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction

    Directory of Open Access Journals (Sweden)

    Obradović Slobodan

    2004-01-01

    Full Text Available Background. Experimental and first clinical studies suggest that the transplantation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial infarction. Aim. This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction. Methods and results. Four male patients (age range 47-68 years with the first extensive anterior, ST elevation, acute myocardial infarction (AMI, were treated by primary angioplasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centrifuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamin stress echocardiography testing and single-photon emission computed tomography (SPECT 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Holter ECG showed only isolated ventricular ectopic beats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction. Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction

  5. Proper Sizing of Circulation Pumps

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Nørgaard, Jørgen

    2007-01-01

    , but the results can be applied to Europe in general. Despite the small sample of houses involved in the test, 15 houses, some rather safe conclusions can be drawn from the results, which showed that newly developed pumps with power consumption around 5-8 W, can perform the task of circulating the water...... as well as their pollution during operation. Policy measures are proposed of how to ensure that in the future only such energy saving pumps are installed. Furthermore, on the basis of the historic experiences with circulation pumps some con¬clusions are drawn on how to investigate, develop and market new...

  6. Vascular potassium channels in NVC.

    Science.gov (United States)

    Yamada, K

    2016-01-01

    It has long been proposed that the external potassium ion ([K(+)]0) works as a potent vasodilator in the dynamic regulation of local cerebral blood flow. Astrocytes may play a central role for producing K(+) outflow possibly through calcium-activated potassium channels on the end feet, responding to a rise in the intracellular Ca(2+) concentration, which might well reflect local neuronal activity. A mild elevation of [K(+)]0 in the end feet/vascular smooth muscle space could activate Na(+)/K(+)-ATPase concomitant with inwardly rectifying potassium (Kir) channels in vascular smooth muscle cells, leading to a hyperpolarization of vascular smooth muscle and relaxation of smooth muscle actin-positive vessels. Also proposed notion is endothelial calcium-activated potassium channels and/or inwardly rectifying potassium channel-mediated hyperpolarization of vascular smooth muscle. A larger elevation of [K(+)]0, which may occur pathophysiologically in such as spreading depression or stroke, can trigger a depolarization of vascular smooth muscle cells and vasoconstriction instead. PMID:27130411

  7. Vascular calcification: Inducers and inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Donghyun, E-mail: dhlee@cau.ac.kr [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)

    2011-09-15

    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  8. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter;

    1994-01-01

    to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

  9. Endothelial progenitors in sepsis: vox clamantis in deserto?

    Science.gov (United States)

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the regenerative capacity of mobilized EPCs and the dissociation between the numerical value and clonogenic competence. Attempting to restore the competence to EPCs should be a priority in the future. PMID:21489327

  10. Evolutionary Models for Type Ib/c Supernova Progenitors

    OpenAIRE

    Yoon, Sung-Chul

    2015-01-01

    Type Ib/c supernovae (SNe Ib/c) mark the deaths of hydrogen-deficient massive stars. The evolutionary scenarios for SNe Ib/c progenitors involve many important physical processes including mass loss by winds and its metallicity dependence, stellar rotation, and binary interactions. This makes SNe Ib/c an excellent test bed for stellar evolution theory. We review the main results of evolutionary models for SN Ib/c progenitors available in the literature and their confrontation with recent obse...

  11. Cellular plasticity : the good, the bad, and the ugly? Microenvironmental influences on progenitor cell therapy

    NARCIS (Netherlands)

    Moonen, Jan-Renier A. J.; Harmsen, Martin C.; Krenning, Guido

    2012-01-01

    Progenitor cell based therapies have emerged for the treatment of ischemic cardiovascular diseases where there is insufficient endogenous repair. However, clinical success has been limited, which challenges the original premise that transplanted progenitor cells would orchestrate repair. In this rev

  12. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  13. No effect of melatonin to modify surgical-stress response after major vascular surgery: a randomised placebo-controlled trial

    DEFF Research Database (Denmark)

    Kücükakin, B; Wilhelmsen, M; Lykkesfeldt, Jens;

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  14. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  15. Interruption of CD40 Pathway Improves Efficacy of Transplanted Endothelial Progenitor Cells in Monocrotaline Induced Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    YanYun Pan

    2015-05-01

    Full Text Available Background/Aims: Transplantation of endothelial progenitor cells (EPCs plays a therapeutic role in pulmonary arterial hypertension (PAH. Meanwhile, recruitment of progenitors has potential inflammatory effects and exaggerates vascular injury. CD40 pathway is identified as a major player in vascular inflammatory events. In this study, we investigated the role of CD40 pathway in regulating early outgrowth EPC functions, and searched for improvements in PAH cell therapy. Methods: EPCs were isolated from rat bone marrow and cultured for 7 days. After treatment with soluble CD40 ligand (sCD40L for 24 hours, EPC migration, adhesion, proliferation, paracrine and vasculogenesis functions were tested. Rat PAH model was founded by subcutaneous injection of monocrotaline (MCT. Control EPCs or lentivirus vectors (Lv-shRNA-CD40 EPCs were infused via tail vein at day 7, 14, and 21 after MCT injection. Therapeutic effects were evaluated at day 28. Results: sCD40L dose-dependently impaired EPC migration, adhesion, proliferation, and vasculogenesis functions. However, paracrine effects of soluble intercellular adhesion molecule-1, vascular endothelial growth factor and interleukin-6 were dose-dependently improved by sCD40L. Control EPC-derived conditioned medium protected endothelial cell in vitro vasculogenesis, while sCD40L-pretreated ones showed detrimental effects. After MCT injection, sCD40L levels in rat serum increased gradually. Other than in vitro results, benefits of both two EPC treatments were obvious, even taken at day 21. Benefits of control EPCs wore off over time, but those of Lv-shRNA-CD40 EPCs were more effective and enduring, as characterized by both ameliorated rat hemodynamic and reversed vascular remodeling. Furthermore, Lv-shRNA-CD40 EPCs integrated into endothelium better, rather than into adventitia and media. Conclusion: sCD40L impaired protective effects of EPCs. Traditional EPC treatments were limited in PAH, while interruption of CD

  16. Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Liana Zucco

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant vascular disorder. Circulating angiogenic cells (CACs play an important role in vascular repair and regeneration. This study was designed to examine the function of CACs derived from patients with HHT. Peripheral blood mononuclear cells (PBMNCs isolated from patients with HHT and age- and gender-matched healthy volunteers were assessed for expression of CD34, CD133 and VEGF receptor 2 by flow cytometry. PBMNCs were cultured to procure early outgrowth CACs. Development of endothelial cell (EC phenotype in CACs was analyzed by fluorescence microscopy. CAC apoptosis was assayed with Annexin V staining, and CAC migration assessed by a modified Boyden chamber assay. mRNA expression of endoglin (ENG, activin receptor-like kinase-1 (ACVLR1 or ALK1 and endothelial nitric oxide synthase (eNOS in CACs was measured by real time RT-PCR. The percentage of CD34+ cells in PBMNCs from HHT patients was significantly higher than in PBMNCs of healthy controls. CACs derived from patients with HHT not only showed a significant reduction in EC-selective surface markers following 7-day culture, but also a significant increase in the rate of basal apoptosis and blunted migration in response to vascular endothelial growth factor and stromal cell-derived factor-1. CACs from HHT patients expressed significantly lower levels of ENG, ALK1 and eNOS mRNAs. In conclusion, CACs from patients with HHT exhibited various functional impairments, suggesting a reduced regenerative capacity of CACs to repair the vascular lesions seen in HHT patients.

  17. Glucose and acute exercise influence factors secreted by circulating angiogenic cells in vitro

    OpenAIRE

    Witkowski, Sarah; Guhanarayan, Gayatri; Burgess, Rachel

    2016-01-01

    Abstract Circulating angiogenic cells (CAC) influence vascular repair through the secretion of proangiogenic factors and cytokines. While CAC are deficient in patients with diabetes and exercise has a beneficial effect on CACs, the impact of these factors on paracrine secretion from CAC is unknown. We aimed to determine whether the in vitro secretion of selected cytokines and nitric oxide (NO) from CAC is influenced by hyperglycemia and acute exercise. Colony‐forming unit CAC (CFU‐CAC) were c...

  18. Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension

    OpenAIRE

    MacKenzie Ross, Robert V.; Toshner, Mark R.; Soon, Elaine; Naeije, Robert; Pepke-Zaba, Joanna

    2013-01-01

    This study analyzed the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance (Ca) in patients with idiopathic pulmonary arterial hypertension (IPAH) and proximal chronic thromboembolic pulmonary hypertension (CTEPH). It has recently been shown that the time constant of the pulmonary circulation (RC time constant), or PVR × Ca, remains unaltered in various forms and severities of pulmonary hypertension, with the exception of left heart failure. We reasoned...

  19. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale

    2011-01-01

    Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

  20. Nitric oxide and coronary vascular endothelium adaptations in hypertension.

    Science.gov (United States)

    Levy, Andrew S; Chung, Justin C S; Kroetsch, Jeffrey T; Rush, James W E

    2009-01-01

    This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca(2+) control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as