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Sample records for circulating vascular progenitors

  1. Circulating vascular progenitor cells and central arterial stiffness in polycystic ovary syndrome.

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    Cecile Dessapt-Baradez

    Full Text Available OBJECTIVE: Subjects with Polycystic ovarian syndrome (PCOS are at increased risk of Type 2 diabetes mellitus (T2DM. The mechanism of this enhanced risk is unclear. Circulating vascular progenitor cells (VPC are immature bone marrow derived cells capable of differentiating into mature endothelial cells. VPC number/function and central arterial stiffness predict cardio-metabolic disease in at-risk populations. DESIGN: We studied VPC and arterial stiffness measures in non-obese PCOS subjects as compared to age and body mass index (BMI matched healthy controls in a cross-sectional study. METHODS: Fourteen subjects with PCOS and 12 controls of similar age, BMI (all <30 kg/m(2 and metabolic profile were studied. VPC number and in vitro function were studied by flow cytometry and tube formation assays respectively. Augmentation index (AIx, a measure of central arterial stiffness, and central (aortic blood pressures (BP were measured by applanation tonometry. RESULTS: Subjects with PCOS had a reduced number, mean±SEM, of circulating CD34(+133(+ VPCs (317.5±51.0 vs. 558.3±101.2, p = 0.03 and impaired in vitro tube formation (completed tube area 1.0±0.06 vs. 1.2±0.05×10(6 µm(2 p = 0.02. PCOS subjects had significantly higher AIx (18.4±1.9% vs. 4.9±2.0% and this difference remained significant even after adjustments for age, BMI and smoking (p = 0.003 in multivariate analyses. Central systolic and pulse pressure were higher in PCOS subjects but these differences were not statistically significant after adjustment for age. Brachial systolic and pulse pressures were similar. VPC number/function and arterial stiffness or BP measures were not correlated. CONCLUSIONS: Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness. These changes in novel vascular risk markers may explain the enhanced risk of T2DM and CVD in PCOS.

  2. 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.

  3. Circulating perivascular progenitors: a target of PDGFR inhibition.

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    Mancuso, Patrizia; Martin-Padura, Ines; Calleri, Angelica; Marighetti, Paola; Quarna, Jessica; Rabascio, Cristina; Braidotti, Paola; Bertolini, Francesco

    2011-09-15

    Cancer blood vessels consist of two interacting types of cells: inner lining endothelial cells (ECs) and surrounding perivascular cells (pericytes, vascular smooth muscle cells or mural cells). PDGFRbeta(CD140b)+ progenitor perivascular cells (PPC) can differentiate into pericytes and regulate vessel stability and vascular survival in tumors. Similarly to what we have done with circulating ECs and progenitors, we developed a flow cytometry procedure for the enumeration of circulating PPCs and the study of their viability in murine models of cancer and in cancer patients. DNA+CD45-CD31-CD140b+ cells were enumerated by six-colour flow cytometry, their morphology was studied by electron microscopy, PPC specificity confirmed by reverse trascription-PCR (RT-PCR) expression of CD140b mRNA, and viability assessed by Syto16 and 7AAD. In preclinical marrow transplantation studies, 9 ± 4% of circulating PPCs were derived from the marrow donor. PPCs were increased in cancer-bearing mice and in patients affected by some types of cancer. At variance with the kinetic of circulating endothelial progenitors, high-dose cyclophosphamide reduced the number of viable PPCs. The administration of sunitinib, a drug known to inhibit PDGFR, was associated in murine models and in cancer patients with an increase of apoptotic/necrotic circulating PPC, suggesting a direct targeting of these cells. PPC enumeration might be studied as a tool for the definition of the optimal biologic dose of anti-PDGFR drugs and investigated clinically as a possible predictive/prognostic tool in patients receiving anti-PDGFR drugs.

  4. 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.

  5. Regulation of the nascent brain vascular network by neural progenitors.

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    Santhosh, Devi; Huang, Zhen

    2015-11-01

    Neural progenitors are central players in the development of the brain neural circuitry. They not only produce the diverse neuronal and glial cell types in the brain, but also guide their migration in this process. Recent evidence indicates that neural progenitors also play a critical role in the development of the brain vascular network. At an early stage, neural progenitors have been found to facilitate the ingression of blood vessels from outside the neural tube, through VEGF and canonical Wnt signaling. Subsequently, neural progenitors directly communicate with endothelial cells to stabilize nascent brain vessels, in part through down-regulating Wnt pathway activity. Furthermore, neural progenitors promote nascent brain vessel integrity, through integrin αvβ8-dependent TGFβ signaling. In this review, we will discuss the evidence for, as well as questions that remain, regarding these novel roles of neural progenitors and the underlying mechanisms in their regulation of the nascent brain vascular network.

  6. 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.

  7. 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.

  8. Flow cytometric data analysis of circulating progenitor cell stability

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    Ernestine A. Mahar

    2017-02-01

    We performed a quality control assessment of the stability of circulating blood progenitor cells in blood samples stored at 4 °C, to determine the time period during which blood samples can be analyzed and yield consistent data for progenitor cell content. Healthy volunteers (n=6 were recruited and underwent phlebotomy, and blood was stored in EDTA tubes at 4 °C. Flow cytometry was performed to quantitate progenitor cell subsets at 0–4 h, 24 h, and 48 h post phlebotomy. All processed samples were fixed with 1% Paraformaldehyde and 1,000,000 total data events were collected. We found no significant differences in PC data for both CD34+ (P=0.68 for one-way ANOVA and CD34+/CD133+ (P=0.74 for one-way ANOVA.

  9. Flow cytometric data analysis of circulating progenitor cell stability.

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    Mahar, Ernestine A; Mou, Liping; Hayek, Salim S; Quyyumi, Arshed A; Waller, Edmund K

    2017-02-01

    A recent publication by Mekonnen et al. demonstrated that among women with non-obstructive coronary artery disease, higher levels of circulating progenitor cells in the blood (CPC), were associated with impaired coronary flow reserve [1]. We performed a quality control assessment of the stability of circulating blood progenitor cells in blood samples stored at 4 °C, to determine the time period during which blood samples can be analyzed and yield consistent data for progenitor cell content. Healthy volunteers (n=6) were recruited and underwent phlebotomy, and blood was stored in EDTA tubes at 4 °C. Flow cytometry was performed to quantitate progenitor cell subsets at 0-4 h, 24 h, and 48 h post phlebotomy. All processed samples were fixed with 1% Paraformaldehyde and 1,000,000 total data events were collected. We found no significant differences in PC data for both CD34+ (P=0.68 for one-way ANOVA) and CD34+/CD133+ (P=0.74 for one-way ANOVA).

  10. Derivation of multipotent progenitors from human circulating CD14+ monocytes.

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    Seta, Noriyuki; Kuwana, Masataka

    2010-07-01

    Circulating CD14(+) monocytes are originated from hematopoietic stem cells in the bone marrow and believed to be committed precursors for phagocytes, such as macrophages. Recently, we have reported a primitive cell population termed monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMCs are derived from circulating CD14(+) monocytes, but circulating precursors for MOMCs still remain undetermined. Comparative analysis of gene expression profiles of MOMCs and other monocyte-derived cells has revealed that embryonic stem cell markers, Nanog and Oct-4, are specifically expressed by MOMCs. In vitro generation of MOMCs requires binding to fibronectin and exposure to soluble factors derived from activated platelets. MOMCs contain progenitors with capacity to differentiate into a variety of nonphagocytes, including bone, cartilage, fat, skeletal and cardiac muscle, neuron, and endothelium, indicating that circulating monocytes are more multipotent than previously thought. In addition, MOMCs are capable of promoting ex vivo expansion of human hematopoietic progenitor cells through direct cell-to-cell contact and secretion of a variety of hematopoietic growth factors. These findings obtained from the research on MOMCs indicate that CD14(+) monocytes in circulation are involved in a variety of physiologic functions other than innate and acquired immune responses, such as repair and regeneration of the damaged tissue.

  11. 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.

  12. Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome.

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    Timeus, Fabio; Crescenzio, Nicoletta; Baldassarre, Giuseppina; Doria, Alessandra; Vallero, Stefano; Foglia, Luiselda; Pagliano, Sara; Rossi, Cesare; Silengo, Margherita Cirillo; Ramenghi, Ugo; Fagioli, Franca; Cordero di Montezemolo, Luca; Ferrero, Giovanni Battista

    2013-08-01

    Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis>1,000/µl. Ten out of the 27 NS patients showed monocytosis>1,000/µl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/µl; range, 44-232) with a low rate of apoptosis (median, 2.1%; range, 0.4-12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/µl, 205.7; range, 58-1374; median apoptotic rate, 1.4%; range, 0.2-2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/µl, 4.9; range, 1.3-17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the

  13. 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

  14. 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.

  15. 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.

  16. End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells

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    Westerweel, Peter E; Hoefer, Imo E; Blankestijn, Peter J; de Bree, Petra; Groeneveld, Dafna; van Oostrom, Olivia; Braam, Branko; Koomans, Hein A; Verhaar, Marianne C

    2007-01-01

    Patients with end-stage renal disease (ESRD) on hemodialysis have an increased risk of cardiovascular disease (CVD). Circulating endothelial progenitor cells (EPC) contribute to vascular regeneration and repair, thereby protecting against CVD. However, circulating smooth muscle progenitor cells (SPC

  17. Circulating endothelial progenitor cells, microvascular density and fibrosis in obesity before and after bariatric surgery.

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    De Ciuceis, Carolina; Rossini, Claudia; Porteri, Enzo; La Boria, Elisa; Corbellini, Claudia; Mittempergher, Francesco; Di Betta, Ernesto; Petroboni, Beatrice; Sarkar, Annamaria; Agabiti-Rosei, Claudia; Casella, Claudio; Nascimbeni, Riccardo; Rezzani, Rita; Rodella, Luigi F; Bonomini, Francesca; Agabiti-Rosei, Enrico; Rizzoni, Damiano

    2013-06-01

    It is not known whether, in obesity, the capillary density or the number of circulating endothelial progenitor cells (EPCs) are reduced, or whether fibrosis of small vessels is also present. In addition, possible effects of weight reduction on these parameters have never been evaluated. Therefore, we investigated EPCs and capillary density in 25 patients with severe obesity, all submitted to bariatric surgery, and in 18 normotensive lean subjects and 12 hypertensive lean patients as controls. All patients underwent a biopsy of subcutaneous fat during bariatric surgery. In five patients, a second biopsy was obtained after consistent weight loss, about 1 year later, during a surgical intervention for abdominoplasty. EPCs and capillary density were reduced in obesity, and EPCs were significantly increased after weight reduction. Vascular collagen content was clearly increased in obese patients. No significant difference in vascular collagen was observed between normotensive obese patients and hypertensive obese patients. After pronounced weight reduction, collagen content was nearly normalized. No difference in stress-strain relation was observed among groups or before and after weight loss. In conclusion, our data suggest that microvascular rarefaction occurs in obesity. EPCs were significantly reduced in obese patients. Pronounced weight loss induced by bariatric surgery seems to induce a significant improvement of EPC number, but not of capillary rarefaction. A pronounced fibrosis of subcutaneous small resistance arteries is present in obese patients, regardless of the presence of increased blood pressure values. Consistent weight loss induced by bariatric surgery may induce an almost complete regression of microvascular fibrosis.

  18. Effect of antihypertensive treatment on circulating endothelial progenitor cells in patients with mild essential hypertension.

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    de Ciuceis, Carolina; Pilu, Annamaria; Rizzoni, Damiano; Porteri, Enzo; Muiesan, Maria Lorenza; Salvetti, Massimo; Paini, Anna; Belotti, Eugenia; Zani, Francesca; Boari, Gianluca E M; Rosei, Claudia Agabiti; Rosei, Enrico Agabiti

    2011-04-01

    It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.

  19. Circulating and Vascular Bioactive Factors during Hypertension in Pregnancy.

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    Tanbe, Alain F; Khalil, Raouf A

    2010-03-01

    Normal pregnancy is associated with significant vascular remodeling in the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. The pregnancy-associated vascular changes are largely due to alterations in the amount/activity of vascular mediators released from the endothelium, vascular smooth muscle and extracellular matrix. The endothelium releases vasodilator substances such as nitric oxide, prostacyclin and hyperpolarizing factor as well as vasoconstrictor factors such as endothelin, angiotensin II and thromboxane A(2). Vascular smooth muscle contraction is mediated by intracellular free Ca(2+) concentration ([Ca(2+)](i)), and [Ca(2+)](i) sensitization pathways such as protein kinase C, Rho-kinase and mitogen-activated protein kinase. Extracellular matrix and vascular remodeling are regulated by matrix metalloproteases. Hypertension in pregnancy and preeclampsia are major complications and life threatening conditions to both the mother and fetus, precipitated by various genetic, dietary and environmental factors. The initiating mechanism of preeclampsia and hypertension in pregnancy is unclear; however, most studies have implicated inadequate invasion of cytotrophoblasts into the uterine artery, leading to reduction in the uteroplacental perfusion pressure and placental ischemia/hypoxia. This placental hypoxic state is thought to induce the release of several circulating bioactive factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and vascular receptor antibodies. Increases in the plasma levels and vascular content of these factors during pregnancy could cause an imbalance in the vascular mediators released from the endothelium, smooth muscle and extracellular matrix, and lead to severe vasoconstriction and hypertension. This review will discuss the interactions between the various circulating bioactive factors and

  20. Update on the pathogenesis of Scleroderma: focus on circulating progenitor cells

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    Brunasso, Alexandra Maria Giovanna; Massone, Cesare

    2016-01-01

    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 +, CD34 low/−, 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

  1. Circulating vascular endothelial growth factor during the normal menstrual cycle

    NARCIS (Netherlands)

    Kusumanto, YH; Hospers, GAP; Sluiter, WJ; Dam, WA; Meijer, C; Mulder, NH

    2004-01-01

    Background: The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle. Materials and Methods: VEGF levels in serum and whole blood w

  2. Role of endothelin in uteroplacental circulation and fetal vascular function.

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    Paradis, Alexandra; Zhang, Lubo

    2013-09-01

    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 subtypes 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 and a vasodilator effect via its action in endothelial cells. Both receptors play a key role in maintaining circulatory homeostasis and vascular function. Changes in ET-1 expression are found in various disease states, and overexpression of ET-1 is observed in hypertension and preeclampsia in pregnancy. Placental localization of ET-1 implies a key role in regulating the uteroplacental circulation. Additionally, ET-1 is important in the fetal circulation and is involved in the pulmonary circulation and closure of the ductus arteriosus after birth, as well as fetal growth constriction in utero. ET receptor antagonists and nitric oxide donors may provide therapeutic potential in treating conditions associated with overexpression of ET and hypertension.

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

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    Kalender G

    2016-12-01

    Full Text Available G Kalender,1 A Kornberger,2 M Lisy,1 Andres Beiras-Fernandez,2 UA Stock2 1Deparment of General, Thoracic and Vascular Surgery, Hoechst Hospital, 2Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany Aim: Endothelial progenitor cells (EPCs are primitive cells found in the bone marrow and peripheral blood (PB. In particular, the potential of EPCs to differentiate into mature endothelial cells remains of high interest for clinical applications such as bio-functionalized patches for autologous seeding after implantation. The objective of this study was to determine EPCs’ kinetics in patients undergoing carotid artery thromboendarterectomy (CTEA and patch angioplasty. Methods: Twenty CTEA patients were included (15 male, mean age 76 years. PB samples were taken at 1 day preoperatively, and at 1, 3, and 5 days postoperatively. Flow cytometric analysis was performed for CD34, CD133, KDR, and CD45. Expression of KDR, SDF-1α, and G-CSF was analyzed by means of enzyme-linked immunosorbent assay. Results: Fluorescence-activated cell sorting analysis revealed 0.031%±0.016% (% of PB mononuclear cells KDR+ cells and 0.052%±0.022% CD45-/CD34+/CD133+ cells, preoperatively. A 33% decrease of CD45–/CD34+/CD133+ cells was observed at day 1 after surgery. However, a relative number (compared to initial preoperative values of CD45-/CD34+/CD133+ cells was found on day 3 (82% and on day 5 (94% postoperatively. More profound upregulated levels of CD45–CD34+/CD133+ cells were observed for diabetic (+47% compared to nondiabetic and male (+38% compared to female patients. No significant postoperative time-dependent differences were found in numbers of KDR+ cells and the concentrations of the cytokines KDR and G-CSF. However, the SDF-1α levels decreased significantly on day 1 postoperatively but returned to preoperative levels by day 3. Conclusion: CTEA results in short-term downregulation of circulating

  4. Uteroplacental circulation and fetal vascular function and development.

    Science.gov (United States)

    Thornburg, Kent L; Louey, Samantha

    2013-09-01

    Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Science.gov (United States)

    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.

  8. 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.

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

    Science.gov (United States)

    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.

  10. 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

  11. Testosterone replacement therapy can increase circulating endothelial progenitor cell number in men with late onset hypogonadism.

    Science.gov (United States)

    Liao, C-H; Wu, Y-N; Lin, F-Y; Tsai, W-K; Liu, S-P; Chiang, H-S

    2013-07-01

    Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. A low EPC number can be considered as an independent predictor of endothelial dysfunction and future cardiovascular events. Recent evidence shows that patients with hypogonadal symptoms without other confounding risk factors have a low number of circulating progenitor cells (PCs) and EPCs, thus highlighting the role of testosterone in the proliferation and differentiation of EPCs. Here, we investigate if testosterone replacement therapy (TRT) can increase circulating EPC number in men with late onset hypogonadism. Forty-six men (age range, 40-73 years; mean age, 58.3 years) with hypogonadal symptoms were recruited, and 29 men with serum total testosterone (TT) levels less than 350 ng/dL received TRT using transdermal testosterone gel (Androgel; 1% testosterone at 5 g/day) for 12 months. Circulating EPC numbers (per 100 000 monocytes) were calculated using flow cytometry. There was no significant association between serum TT levels and the number of circulating EPCs before TRT. Compared with the number of mean circulating EPCs at baseline (9.5 ± 6.2), the number was significantly higher after 3 months (16.6 ± 11.1, p = 0.027), 6 months (20.3 ± 15.3, p = 0.006) and 12 months (27.2 ± 15.5, p = 0.017) of TRT. Thus, we conclude that serum TT levels before TRT are not significantly associated with the number of circulating EPCs in men with late onset hypogonadism. However, TRT can increase the number of circulating EPCs, which implies the benefit of TRT on endothelial function in hypogonadal men.

  12. Lack of increased expression of cell surface markers for circulating fibrocyte progenitors in limited scleroderma.

    Science.gov (United States)

    Russo, R; Medbury, H; Guiffre, A; Englert, H; Manolios, N

    2007-07-01

    The aetiology and pathogenesis of scleroderma is incompletely understood. Recently, a cell called the fibrocyte has been shown to be derived from circulating monocytes with the ability to produce collagen. The aim of this study was to evaluate differences in the cell surface characteristics of circulating fibrocyte progenitors (monocytes) in patients with limited scleroderma compared to controls. A case-control study was performed in eight patients with limited scleroderma, which were matched with eight controls. Three-colour flow cytometry was used to assess the relative expression of cell surface markers. Statistical analysis then compared the relative expression between the two groups. In this preliminary study, there were no significant differences in the expression of circulating monocyte surface molecules involved with cell transformation, function, or migration presumed to give rise to fibrocytes, in a population of patients with limited scleroderma. Various explanations for the results are discussed.

  13. Angiotensin II impairs endothelial progenitor cell number and function in vitro and in vivo: implications for vascular regeneration.

    Science.gov (United States)

    Endtmann, Cathleen; Ebrahimian, Talin; Czech, Thomas; Arfa, Omar; Laufs, Ulrich; Fritz, Mathias; Wassmann, Kerstin; Werner, Nikos; Petoumenos, Vasileios; Nickenig, Georg; Wassmann, Sven

    2011-09-01

    Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E-deficient mice compared with transplantation of apolipoprotein E-deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT(1)-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT(1)-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1-dependent proapoptotic pathways impairs EPCs in

  14. 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.

  15. Circulating progenitors following high-dose sequential (HDS) chemotherapy with G-CSF: short intervals between drug courses severely impair progenitor mobilization.

    Science.gov (United States)

    Tarella, C; Caracciolo, D; Gavarotti, P; Bondesan, P; Cherasco, C; Omedè, P; Bregni, M; Siena, S; Gianni, A M; Pileri, A

    1995-08-01

    Sequential administration of high-dose chemotherapy courses possibly allows extensive in vivo purging before circulating progenitor collection for autograft. To evaluate whether progenitor cell mobilization was negatively affected by repeated high-dose chemotherapy courses, we studied 23 lymphoma patients undergoing the HDS regimen. The scheme includes the sequential administration of cyclophosphamide (CY) given at 7 g/m2 and etoposide (VP16) given at 2 g/m2, each followed by G-CSF (filgrastim) at 5 micrograms/kg/day. Eleven patients received the standard HDS sequence, with a short interval between first and second myelotoxic courses of less than 45 days (median: 30 days); the remaining 12 patients received a modified HDS where the interval between first and second high-dose course was protracted over 2 months (median: 70 days); in this latter group, 2 to 4 conventional debulking courses were delivered prior to HDS. In patients receiving the standard HDS, progenitor mobilization following the first course was consistently high (median circulating CFU-GM/ml peak value: 29,022); however, significantly lower values were observed at the second course (median CFU-GM/ml peak value 3757, P = 0.002). Circulating BFU-E and CD34+ cell values paralleled those of CFU-GM. No significant difference was observed in progenitor mobilization following either course in patients receiving HDS with extended interval (median circulating CFU-GM/ml peak value: 14,363 vs 9208, at first and second course respectively, P = 0.27). Eleven patients had their progenitor cells harvested following the second delayed course and 2-4 leucaphereses allowed very satisfactory harvests in all of them (CFU-GM/kg ranging from 39-340 x 10(4)).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Neurovascular Recovery via Cotransplanted Neural and Vascular Progenitors Leads to Improved Functional Restoration after Ischemic Stroke in Rats

    Directory of Open Access Journals (Sweden)

    Jia Li

    2014-07-01

    Full Text Available The concept of the “neurovascular unit,” emphasizing the interactions between neural and vascular components in the brain, raised the notion that neural progenitor cell (NPC transplantation therapy aimed at neural repair may be insufficient for the treatment of ischemic stroke. Here, we demonstrate that enhanced neurovascular recovery via cotransplantation of NPCs and embryonic stem cell-derived vascular progenitor cells (VPCs in a rat stroke model is correlated with improved functional recovery after stroke. We found that cotransplantation promoted the survival, migration, differentiation, and maturation of neuronal and vascular cells derived from the cotransplanted progenitors. Furthermore, it triggered an increased generation of VEGF-, BDNF-, and IGF1-expressing neural cells derived from the grafted NPCs. Consistently, compared with transplantation of NPCs alone, cotransplantation more effectively improved the neurobehavioral deficits and attenuated the infarct volume. Thus, cotransplantation of NPCs and VPCs represents a more effective therapeutic strategy for the treatment of stroke than transplantation of NPCs alone.

  17. 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.

  18. Differential effects of nebivolol and metoprolol on arterial stiffness, circulating progenitor cells, and oxidative stress.

    Science.gov (United States)

    Hayek, Salim S; Poole, Joseph C; Neuman, Robert; Morris, Alanna A; Khayata, Mohamed; Kavtaradze, Nino; Topel, Matthew L; Binongo, Jose G; Li, Qunna; Jones, Dean P; Waller, Edmund K; Quyyumi, Arshed A

    2015-03-01

    Unlike traditional beta receptor antagonists, nebivolol activates nitric oxide. We hypothesized that therapy with nebivolol compared with metoprolol would improve arterial stiffness, increase levels of circulating progenitor cells (PC), and decrease oxidative stress (OS). In a randomized, double-blind, cross-over study, 30 hypertensive subjects received either once daily nebivolol or metoprolol succinate for 3 months each. Pulse wave velocity and augmentation index were measured using tonometry. Flow cytometry was used to measure circulating PC. OS was measured as plasma aminothiols. Measurements were performed at baseline, and repeated at 3 and 6 months. No significant differences were present between the levels of OS, arterial stiffness, and PC numbers during treatment with metoprolol compared with nebivolol. In subgroup analyses of beta-blocker naïve subjects (n = 19), nebivolol reduced pulse wave velocity significantly compared with metoprolol (-1.4 ± 1.9 vs. -0.1 ± 2.2; P = .005). Both nebivolol and metoprolol increased circulating levels of CD34+/CD133 + PC similarly (P = .05), suggesting improved regenerative capacity.

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

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    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.

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

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    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

  1. 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

  2. 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.

  3. 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.

  4. Stepwise optimization of the procedure for assessment of circulating progenitor cells in patients with myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Yu-Xin Cui

    Full Text Available 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 red blood cell lysis buffer, FMO or isotype controls to identify rare cell populations from background noise, optimal antibody dilutions and conditions of sample storage. We herein propose improvements in critical steps of CPC isolation, antigenic characterization and determination of functional competence for final application in a prospective investigation of CPCs as a biomarker of outcome following acute myocardial infarction. METHODS AND FINDINGS: In this validation study, we refined the standard operating procedure (SOP for flow cytometry characterisation and functional analysis of CPCs from the first 18 patients of the Progenitor Cell Response after Myocardial Infarction Study (ProMIS. ProMIS aims to verify the prognostic value of CPCs in patients with either ST elevation or non-ST elevation myocardial infarction with or without diabetes mellitus, using cardiac magnetic resonance imaging (MRI for assessment of ventricular function as a primary endpoint. Results indicate crucial steps for SOP implementation, namely timely cell isolation after sampling, use of appropriate lysis buffer to separate blood cell types and minimize the acquisition events during flow cytometry, adoption of proper fluorophore combination and antibody titration for multiple antigenic detection and introduction of counting beads for precise quantification of functional CPC activity in migration assay. CONCLUSION AND SIGNIFICANCE: With systematic specification of factors influencing

  5. 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

    2007-08-03

    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.

  6. Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul.

    Science.gov (United States)

    Dome, P; Teleki, Z; Rihmer, Z; Peter, L; Dobos, J; Kenessey, I; Tovari, J; Timar, J; Paku, S; Kovacs, G; Dome, B

    2009-05-01

    Although depression is known to be an independent risk factor for cardiovascular disorders, the mechanisms behind this connection are not well understood. However, the reduction in the number of endothelial progenitor cells (EPCs) in patients with cardiovascular risk factors has led us to hypothesize that depression influences the number of EPCs. EPCs labeled with CD34, CD133 and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood (PB) of 33 patients with a current episode of major depression and of 16 control subjects. Mature (CD34+/VEGFR2+) and immature (CD133+/VEGFR2+) EPC counts were decreased in patients (vs controls; Pdepressive symptoms (Pquantitative RT-PCR approach, we measured CD34, CD133 and VEGFR2 mRNA levels of PB samples and found a net trend toward a decrease in all the investigated EPC-specific mRNA levels in patients as compared with controls. However, statistical significance was reached only for VEGFR2 and CD133 levels (Pdepression.

  7. 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

  8. The angiogenic gene profile of circulating endothelial progenitor cells from ischemic stroke patients

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    Navarro-Sobrino Míriam

    2013-02-01

    Full Text Available Abstract Background The identification of circulating endothelial progenitor cells (EPCs has introduced new possibilities for cell-based treatments for stroke. We tested the angiogenic gene expression of outgrowth endothelial cells (OECs, an EPC subtype capable to shape vessel structures. Methods OECs (at colony or mature stages from ischemic stroke patients (n=8 were characterized using the RT2 ProfilerTM human angiogenesis PCR Array, and human microvascular endothelial cells (hCMEC/D3 were used as an expression reference of endothelial cells. Results Colony-OECs showed higher expression of CCL2, ID3, IGF-1, MMP9, TGFBR1, TNFAIP2, TNF and TGFB1. However, BAI-1, NRP2, THBS1, MMP2 and VEGFC expression was increased in mature-OECs (p Conclusion Our study shows that OECs from stroke patients present higher levels of pro-angiogenic factors at early stages, decreasing in mature OECs when they become more similar to mature microvascular endothelial cells.

  9. 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.

  10. 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.

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

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    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

  13. 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

  14. Fli+ etsrp+ hemato-vascular progenitor cells proliferate at the lateral plate mesoderm during vasculogenesis in zebrafish.

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    Chang Zoon Chun

    Full Text Available BACKGROUND: Vasculogenesis, the de novo formation of blood vessels from precursor cells is critical for a developing embryo. However, the signals and events that dictate the formation of primary axial vessels remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we use ets-related protein-1 (etsrp, which is essential for vascular development, to analyze the early stages of vasculogenesis in zebrafish. We found etsrp(+ cells of the head, trunk and tail follow distinct developmental sequences. Using a combination of genetic, molecular and chemical approaches, we demonstrate that fli(+etsrp(+ hemato-vascular progenitors (FEVPs are proliferating at the lateral plate mesoderm (LPM. The Shh-VEGF-Notch-Hey2 signaling pathway controls the proliferation process, and experimental modulation of single components of this pathway alters etsrp(+ cell numbers at the LPM. CONCLUSIONS/SIGNIFICANCE: This study for the first time defines factors controlling proliferation, and cell numbers of pre-migratory FEVPs in zebrafish.

  15. Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation.

    Science.gov (United States)

    Barman, S A; Senteno, E; Smith, S; Taylor, A E

    1989-10-01

    Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.

  16. 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.

  17. Circulating human CD34(+) progenitor cells modulate neovascularization and inflammation in a nude mouse model

    NARCIS (Netherlands)

    van der Strate, B. W. A.; Popa, E. R.; Schipper, M.; Brouwer, L. A.; Hendriks, M.; Harmsen, M. C.; van Luyn, M. J. A.

    2007-01-01

    CD34(+) progenitor cells hold promise for therapeutic neovascularization in various settings. In this study, the role of human peripheral blood CD34(+) cells in neovascularization and inflammatory cell recruitment was longitudinally studied in vivo. Human CD34(+) cells were incorporated in Matrigel,

  18. A human postnatal lymphoid progenitor capable of circulating and seeding the thymus.

    Science.gov (United States)

    Six, Emmanuelle M; Bonhomme, Delphine; Monteiro, Marta; Beldjord, Kheira; Jurkowska, Monika; Cordier-Garcia, Corinne; Garrigue, Alexandrine; Dal Cortivo, Liliane; Rocha, Benedita; Fischer, Alain; Cavazzana-Calvo, Marina; André-Schmutz, Isabelle

    2007-12-24

    Identification of a thymus-seeding progenitor originating from human bone marrow (BM) constitutes a key milestone in understanding the mechanisms of T cell development and provides new potential for correcting T cell deficiencies. We report the characterization of a novel lymphoid-restricted subset, which is part of the lineage-negative CD34(+)CD10(+) progenitor population and which is distinct from B cell-committed precursors (in view of the absence of CD24 expression). We demonstrate that these Lin(-)CD34(+)CD10(+)CD24(-) progenitors have a very low myeloid potential but can generate B, T, and natural killer lymphocytes and coexpress recombination activating gene 1, terminal deoxynucleotide transferase, PAX5, interleukin 7 receptor alpha, and CD3epsilon. These progenitors are present in the cord blood and in the BM but can also be found in the blood throughout life. Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus.

  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. 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...

  1. 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.

  2. 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...

  3. 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.

  4. 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

    2016-01-01

    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

  5. Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease

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    Cheng-Jui Lin

    2016-12-01

    Full Text Available Background/Aims: Indoxyl sulfate (IS is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD. We explored the effect of IS on human early endothelial progenitor cells (EPCs and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD, pulse wave velocity (PWV, ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS and free IS (F-IS were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR, hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

  6. SDF1 gene variation is associated with circulating SDF1alpha level and endothelial progenitor cell number: the Bruneck Study.

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    Qingzhong Xiao

    Full Text Available BACKGROUND: Stromal cell-derived factor-1 (SDF1 and its receptor CXC chemokine receptor 4 (CXCR4 play a critical role in progenitor cell homing, mobilization and differentiation. It would be interesting to assess the predictive value of SDF-1alpha level for EPC number, and to ascertain whether there is a relationship between SDF1 gene variation, plasma SDF-1alpha level, and the number and function of circulating EPCs. We also tested whether EPC number and function was related to CXCR4 gene variation. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped a cohort of individuals who participated in the Bruneck Study for single nucleotide polymorphisms (SNPs in the SDF1 and CXCR4 genes, and measured blood SDF1alpha level as well as EPC number and function. SDF1alpha levels were correlated with age, gender, alcohol consumption, circulating reticulocyte numbers, and concentrations of matrix metalloproteinase-9, C-reactive protein, cystatin C, fibrinogen and homocytein. In blood samples taken in 2005, EPC number was inversely associated with SDF1alpha level (p<0.001. EPC number in 2005 was also inversely associated with SDF1alpha level in 2000 (p = 0.009, suggesting a predictive value of plasma SDF1alpha level for EPC number. There was an association between the SDF1 gene rs2297630 SNP A/A genotype, increased SDF1alpha level (p = 0.002 and lower EPC number (p = 0.006. CONCLUSIONS: Our data indicate that a SDF1 gene variation (rs2297630 has an influence on SDF1alpha level and circulating EPC number, and that plasma SDF1alpha level is a predictor of EPC number.

  7. 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.

  8. 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.

  9. 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......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...

  10. Neurogenic potential of progenitors derived from human circulating CD14+ monocytes.

    Science.gov (United States)

    Kodama, Hiroaki; Inoue, Takafumi; Watanabe, Ryuichi; Yasutomi, Daisuke; Kawakami, Yutaka; Ogawa, Satoshi; Mikoshiba, Katsuhiko; Ikeda, Yasuo; Kuwana, Masataka

    2006-04-01

    We previously reported a primitive cell fraction derived from human circulating CD14+ monocytes, named monocyte-derived multipotential cells (MOMC), that can differentiate along mesenchymal lineages, including bone, cartilage, fat, skeletal muscle and cardiac muscle. In this study, we investigated whether MOMC can differentiate into the neuronal lineage. MOMC were fluorescently labelled and cocultivated with a primary culture of rat neurons for up to 4 weeks. The protein and gene expressions of neuron-specific markers in the human MOMC were evaluated over time using immunohistochemistry, in situ hybridization and reverse transcription followed by PCR. Shortly after cocultivation with rat neurons, nearly all the MOMC expressed early neuroectodermal markers, Mash1, Neurogenin2 and NeuroD, together with nestin, an intermediate filament expressed in neurogenesis. After 14 days of coculture, a subpopulation of MOMC displayed a multipolar morphology with elongated neurites and expressed mature neuron-specific markers, including neurofilament, microtubule-associated protein type 2, beta3-tubulin, NeuN and Hu. Transdifferentiation of monocytes into the neuroectodermal lineage was shown by the simultaneous expression of proneural markers and CD45/CD14 early in the differentiation process. The cocultivated MOMC retained their proliferative capacity for at least 16 days. Finally, the neuronal differentiation of MOMC was observed when they were cultured with neurons without cell-to-cell contact. The capacity of MOMC to differentiate into both mesodermal and neuroectodermal lineages suggests that circulating CD14+ monocytes are more multipotential than previously thought.

  11. 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.

  12. Germline variants in ETV6 underlie reduced platelet formation, platelet dysfunction and increased levels of circulating CD34+ progenitors

    Science.gov (United States)

    Poggi, Marjorie; Canault, Matthias; Favier, Marie; Turro, Ernest; Saultier, Paul; Ghalloussi, Dorsaf; Baccini, Veronique; Vidal, Lea; Mezzapesa, Anna; Chelghoum, Nadjim; Mohand-Oumoussa, Badreddine; Falaise, Céline; Favier, Rémi; Ouwehand, Willem H.; Fiore, Mathieu; Peiretti, Franck; Morange, Pierre Emmanuel; Saut, Noémie; Bernot, Denis; Greinacher, Andreas; BioResource, NIHR; Nurden, Alan T.; Nurden, Paquita; Freson, Kathleen; Trégouët, David-Alexandre; Raslova, Hana; Alessi, Marie-Christine

    2017-01-01

    Variants in ETV6, which encodes a transcription repressor of the E26 transformation-specific family, have recently been reported to be responsible for inherited thrombocytopenia and hematologic malignancy. We sequenced the DNA from cases with unexplained dominant thrombocytopenia and identified six likely pathogenic variants in ETV6, of which five are novel. We observed low repressive activity of all tested ETV6 variants, and variants located in the E26 transformation-specific binding domain (encoding p.A377T, p.Y401N) led to reduced binding to corepressors. We also observed a large expansion of megakaryocyte colony-forming units derived from variant carriers and reduced proplatelet formation with abnormal cytoskeletal organization. The defect in proplatelet formation was also observed in control CD34+ cell-derived megakaryocytes transduced with lentiviral particles encoding mutant ETV6. Reduced expression levels of key regulators of the actin cytoskeleton CDC42 and RHOA were measured. Moreover, changes in the actin structures are typically accompanied by a rounder platelet shape with a highly heterogeneous size, decreased platelet arachidonic response, and spreading and retarded clot retraction in ETV6 deficient platelets. Elevated numbers of circulating CD34+ cells were found in p.P214L and p.Y401N carriers, and two patients from different families suffered from refractory anemia with excess blasts, while one patient from a third family was successfully treated for acute myeloid leukemia. Overall, our study provides novel insights into the role of ETV6 as a driver of cytoskeletal regulatory gene expression during platelet production, and the impact of variants resulting in platelets with altered size, shape and function and potentially also in changes in circulating progenitor levels. PMID:27663637

  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. Expression of parathyroid-specific genes in vascular endothelial progenitors of normal and tumoral parathyroid glands.

    Science.gov (United States)

    Corbetta, Sabrina; Belicchi, Marzia; Pisati, Federica; Meregalli, Mirella; Eller-Vainicher, Cristina; Vicentini, Leonardo; Beck-Peccoz, Paolo; Spada, Anna; Torrente, Yvan

    2009-09-01

    Parathyroid tissue is able to spontaneously induce angiogenesis, proliferate, and secrete parathyroid hormone when autotransplanted in patients undergoing total parathyroidectomy. Angiogenesis is also involved in parathyroid tumorigenesis. Here we investigated the anatomical and molecular relationship between endothelial and parathyroid cells within human parathyroid glands. Immunohistochemistry for CD34 antigen identified two subpopulations in normal and tumoral parathyroid glands: one constituted by cells lining small vessels that displayed endothelial antigens (factor VIII, isolectin, laminin, CD146) and the other constituted of single cells scattered throughout the parenchyma that did not express endothelial markers. These parathyroid-derived CD34(+) cells were negative for the hematopoietic and mesenchymal markers CD45, Thy-1/CD90, CD105, and CD117/c-kit; however, a subset of CD34(+) cells co-expressed the parathyroid specific genes glial cell missing B, parathyroid hormone, and calcium sensing receptor. When cultured, these cells released significant amount of parathyroid hormone. Parathyroid-derived CD34(+) cells, but not CD34(-) cells, proliferated slowly and differentiated into mature endothelial cells. CD34(+) cells from parathyroid tumors differed from those derived from normal parathyroid glands as: 1) they were more abundant and mainly scattered throughout the parenchyma; 2) they rarely co-expressed CD146; and 3) a fraction co-expressed nestin. In conclusion, we identified cells expressing endothelial and parathyroid markers in human adult parathyroid glands. These parathyroid/endothelial cells were more abundant and less committed in parathyroid tumors compared with normal glands, showing features of endothelial progenitors, which suggests that they might be involved in parathyroid tumorigenesis.

  16. Potential role of vascular smooth muscle cell-like progenitor cell therapy in the suppression of experimental abdominal aortic aneurysms.

    Science.gov (United States)

    Park, Hyung Sub; Choi, Geum Hee; Hahn, Soli; Yoo, Young Sun; Lee, Ji Youl; Lee, Taeseung

    2013-02-08

    Abdominal aortic aneurysms (AAA) are a growing problem worldwide, yet there is no known medical therapy. The pathogenesis involves degradation of the elastic lamina by two combined mechanisms: increased degradation of elastin by matrix metalloproteinases (MMP) and decreased formation of elastin due to apoptosis of vascular smooth muscle cells (VSMC). In this study, we set out to examine the potential role of stem cells in the attenuation of AAA formation by inhibition of these pathogenetic mechanisms. Muscle-derived stem cells from murine skeletal muscles were isolated and stimulated with PDGF-BB in vitro for differentiation to VSMC-like progenitor cells (VSMC-PC). These cells were implanted in to elastase-induced AAAs in rats. The cell therapy group had decreased rate of aneurysm formation compared to control, and MMP expression at the genetic, protein and enzymatic level were also significantly decreased. Furthermore, direct implantation of VSMC-PCs in the intima of harvested aortas was visualized under immunofluorescent staining, suggesting that these cells were responsible for the inhibition of MMPs and consequent attenuation of AAA formation. These results show a promising role of stem cell therapy for the treatment of AAAs, and with further studies, may be able to reach clinical significance.

  17. 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.

  18. Vitamin D Status in Rheumatoid Arthritis: Inflammation, Arterial Stiffness and Circulating Progenitor Cell Number.

    Directory of Open Access Journals (Sweden)

    Alberto Lo Gullo

    Full Text Available Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA. Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs, including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA.CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP, fibrinogen, pulse wave velocity (PWV, and carotid intima-media thickness (cIMT were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT; vitamin D levels appear also to be inversely associated to fibrinogen.RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.

  19. 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.

  20. Changes in circulating endothelial progenitor cells predict responses of multiple myeloma patients to treatment with bortezomib and dexamethasone

    Directory of Open Access Journals (Sweden)

    L. Wang

    2015-08-01

    Full Text Available Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM patients. We investigated whether circulating endothelial progenitor cells (cEPCs could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16, common responders (n=12, and non-responders (n=18. There were no significant differences among these groups at baseline day 1 (P>0.05. cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/μL vs day 1 (8.4±2.9 cEPCs/μL in good responders (P>0.05. In contrast, cEPC levels increased significantly in the other two groups (P<0.05. SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.

  1. Molecular Characterization of the Interactions between Vascular Selectins and Glycoprotein Ligands on Human Hematopoietic Stem/Progenitor Cells

    KAUST Repository

    Abusamra, Dina

    2016-12-01

    The human bone marrow vasculature constitutively expresses both E-selectin and P-selectin where they interact with the cell-surface glycan moiety, sialyl Lewis x, on circulating hematopoietic stem/progenitor cells (HSPCs) to mediate the essential tethering/rolling step. Although several E-selectin glycoprotein ligands (E-selLs) have been identified, the importance of each E-selL on human HSPCs is debatable and requires additional methodologies to advance their specific involvement. The first objective was to fill the knowledge gap in the in vitro characterization of the mechanisms used by selectins to mediate the initial step in the HSPCs homing by developing a real time immunoprecipitation-based assay on a surface plasmon resonance chip. This novel assay bypass the difficulties of purifying ligands, enables the use of natively glycosylated forms of selectin ligands from any model cell of interest and study its binding affinities under flow. We provide the first comprehensive quantitative binding kinetics of two well-documented ligands, CD44 and PSGL-1, with E-selectin. Both ligands bind monomeric E-selectin transiently with fast on- and off-rates while they bind dimeric E-selectin with remarkably slow on- and off-rates with the on-rate, but not the off-rate, is dependent on salt concentration. Thus, suggest a mechanism through which monomeric selectins mediate initial fast-on and -off binding to capture the circulating cells out of shear-flow; subsequently, tight binding by dimeric/oligomeric selectins is enabled to slow rolling significantly. The second objective is to fully identify and characterize E/P-selectin ligand candidates expressed on CD34+ HSPCs which cause enhanced migration after intravenous transplantation compared to their CD34- counterparts. CD34 is widely recognized marker of human HSPCs but its natural ligand and function on these cells remain elusive. Proteomics identified CD34 as an E-selL candidate on human HSPCs, whose binding to E

  2. SDF1 Gene Variation Is Associated with Circulating SDF1 alpha Level and Endothelial Progenitor Cell Number-The Bruneck Study

    OpenAIRE

    Xiao, Q.; Ye, S.; Oberhollenzer, F; Mayr, A; Jahangiri, M; Willeit, J.; Kiechl, S; Xu, Q.

    2008-01-01

    BACKGROUND: Stromal cell-derived factor-1 (SDF1) and its receptor CXC chemokine receptor 4 (CXCR4) play a critical role in progenitor cell homing, mobilization and differentiation. It would be interesting to assess the predictive value of SDF-1alpha level for EPC number, and to ascertain whether there is a relationship between SDF1 gene variation, plasma SDF-1alpha level, and the number and function of circulating EPCs. We also tested whether EPC number and function was related to CXCR4 gene ...

  3. 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.

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Alexander E. Berezin

    2016-09-01

    Full Text Available 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.

  7. Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells.

    Science.gov (United States)

    Butler, Jason M; Gars, Eric J; James, Daylon J; Nolan, Daniel J; Scandura, Joseph M; Rafii, Shahin

    2012-08-09

    Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that coculture of CD34(+) hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45(+)CD34(+) progenitor cells, and 23-fold expansion of CD45(+) Lin(-)CD34(hi+)CD45RA(-)CD49f(+) stem and progenitor cells over a 12-day period. Compared with cytokines alone, coculture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders.

  8. Analysis of Circulating Vascular Endothelial Growth Factor and Its Soluble Receptors in Patients with Different Forms of Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Julia Jagodzinska

    2015-01-01

    Full Text Available Background. Vascular endothelial growth factor (VEGF is a powerful enhancer of vascular permeability and inflammatory response; however its significance in chronic urticaria is poorly recognised. Aim. To compare free circulating levels of VEGF and its soluble receptors (sVEGFR1 and VEGFR2 in patients with different forms of chronic urticaria. Methods. The concentrations of VEGF and its receptors in plateletpoor plasma (PPP/plasma were measured using enzyme-linked immunosorbent assay in chronic urticaria: (1 chronic spontaneous urticaria (CSU with positive autologous serum skin test (ASST, (2 CSU with negative response to ASST, (3 CSU with concomitant euthyroid Hashimoto’s thyroiditis (CSU/Hashimoto, (4 delayed pressure urticaria (DPU, and the healthy subjects. Results. There were no significant differences in VEGF concentration in PPP between CSU groups and the healthy subjects. Contrary, VEGF concentration was significantly higher in DPU and CSU/Hashimoto patients as compared with the healthy subjects and CSU groups. Furthermore, VEGF value in CSU/Hashimoto patients during the remission was similar to that of the active period and significantly higher than the healthy subjects; VEGF concentration was significantly correlated with TSH. Plasma concentrations of sVEGF1 and sVEGF2 were similar in chronic urticaria patients and the healthy subjects. Conclusions. Increased free circulating VEGF concentration may result from the urticarial process itself as well as concomitant Hashimoto’s thyroiditis.

  9. Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia.

    Science.gov (United States)

    Shah, Dania A; Khalil, Raouf A

    2015-06-15

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca(2+), protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

  10. Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.

    Science.gov (United States)

    Rebourcet, Diane; Wu, Junxi; Cruickshanks, Lyndsey; Smith, Sarah E; Milne, Laura; Fernando, Anuruddika; Wallace, Robert J; Gray, Calum D; Hadoke, Patrick W F; Mitchell, Rod T; O'Shaughnessy, Peter J; Smith, Lee B

    2016-06-01

    The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.

  11. Relation Between Circulating Inflammatory Chemokines and Vascular Characteristics in Healthy, Young Children

    NARCIS (Netherlands)

    Eikendal, Anouk L M; Evelein, Annemieke M V; Uiterwaal, Cuno S P M; van der Ent, Cornelis K; Visseren, Frank L J; Bots, Michiel L; Höfer, Imo E.; den Ruijter, Hester M; Dalmeijer, Geertje W

    2015-01-01

    BACKGROUND: Atherosclerosis begins in childhood with the occurrence of inflammatory vascular wall alterations that are detectable with B-mode ultrasound. Chemokines appear to be involved in the development of these alterations given that they occur early in the atherosclerotic pathway as mediators o

  12. Pathophysiology of vascular endothelium and circulating platelets : implications for coronary revascularisation and treatment

    NARCIS (Netherlands)

    Amoroso, G; van Veldhuisen, DJ; Tio, RA; Mariani, M

    2001-01-01

    Constant vasodilatation, inhibition of platelet and leukocyte adhesion, and local thrombolysis are the mechanisms through which an intact endothelial layer exerts its protective action on coronary circulation. A loss in these features is not only the first step in the development of atherosclerosis,

  13. 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

  14. 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

    . In corresponding blood samples, automated complete blood count was performed, and the number of each cell type was correlated to VEGF concentrations in plasma, serum and lysed whole blood. Finally, the impact of increasing clotting time on the release of VEGF to serum was analysed. RESULTS: Isolated neutrophils......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 plasma, serum and lysed whole blood. METHODS: In 51 colorectal cancer (CRC) patients, circulating T-lymphocytes, B-lymphocytes, monocytes, and granulocytes were isolated by means of immunomagnetic separation. Subsequently, the isolated cells were lysed and VEGF contents in the lysates were determined...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Acute Effects of Different Exercise Protocols on the Circulating Vascular microRNAs -16, -21, and -126 in Trained Subjects

    Science.gov (United States)

    Wahl, Patrick; Wehmeier, Udo F.; Jansen, Felix J.; Kilian, Yvonne; Bloch, Wilhelm; Werner, Nikos; Mester, Joachim; Hilberg, Thomas

    2016-01-01

    Aim: mircoRNAs (miRNAs), small non-coding RNAs regulating gene expression, are stably secreted into the blood and circulating miRNAs (c-miRNAs) may play an important role in cell–cell communication. Furthermore, c-miRNAs might serve as novel biomarkers of the current vascular cell status. Here, we examined how the levels of three vascular c-miRNAs (c-miR-16, c-miR-21, c-miR-126) are acutely affected by different exercise intensities and volumes. Methods: 12 subjects performed 3 different endurance exercise protocols: 1. High-Volume Training (HVT; 130 min at 55% peak power output (PPO); 2. High-Intensity Training (HIT; 4 × 4 min at 95% PPO); 3. Sprint-Interval Training (SIT; 4 × 30 s all-out). c-miRNAs were quantified using quantitative real-time PCR with TaqMan probes at time points pre, 0′, 30′, 60′, and 180′ after each intervention. The expression of miR-126 and miR-21 was analyzed in vitro, in human coronary artery endothelial cells, human THP-1 monocytes, human platelets, human endothelial microparticles (EMPs) and human vascular smooth muscle cells (VSMCs). To investigate the transfer of miRNAs via EMPs, VSMCs were incubated with EMPs. Results: HVT and SIT revealed large increases on c-miR-21 [1.9-fold by HVT (cohen's d = 0.85); 1.5-fold by SIT (cohen's d = 0.85)] and c-miR-126 [2.2-fold by SIT (cohen's d = 1.06); 1.9-fold by HVT (cohen's d = 0.85)] post-exercise compared to pre-values, while HIT revealed only small to moderate changes on c-miRs-21 (cohen's d = −0.28) and c-miR-126 (cohen's d = 0.53). c-miR-16 was only slightly affected by SIT (1.4-fold; cohen's d = 0.57), HVT (1.3-fold; cohen's d = 0.61) or HIT (1.1-fold; cohen's d = 0.2). Further in vitro experiments revealed that miR-126 and miR-21 are mainly of endothelial origin. Importantly, under conditions of endothelial apoptosis, miR-126 and miR-21 are packed from endothelial cells into endothelial microparticles, which were shown to transfer miR-126 into target vascular smooth muscle

  18. Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage.

    Science.gov (United States)

    Wang, Lunchang; Qiu, Ping; Jiao, Jiao; Hirai, Hiroyuki; Xiong, Wei; Zhang, Jifeng; Zhu, Tianqing; Ma, Peter X; Chen, Y Eugene; Yang, Bo

    2017-02-01

    Vascular smooth muscle cells (VSMCs) derived from cardiovascular progenitor cell (CVPC) lineage populate the tunica media of the aortic root. Understanding differentiation of VSMCs from CVPC will further our understanding of the molecular mechanisms contributing to aortic root aneurysms, and thus, facilitate the development of novel therapeutic agents to prevent this devastating complication. It is established that the yes-associated protein (YAP) and Hippo pathway is important for VSMC proliferation and phenotype switch. To determine the role of YAP in differentiation of VSMCs from CVPCs, we utilized the in vitro monolayer lineage specific differentiation method by differentiating human embryonic stem cells into CVPCs, and then, into VSMCs. We found that expression of YAP decreased during differentiation of VSMC from CVPCs. Overexpression of YAP attenuated expression of VSMC contractile markers and impaired VSMC function. Knockdown of YAP increased expression of contractile proteins during CVPC-VSMCs differentiation. Importantly, expression of YAP decreased transcription of myocardin during this process. Overexpression of YAP in PAC1 SMC cell line inhibited luciferase activity of myocardin proximal promoter in a dose dependent and NKX2.5 dependent manners. YAP protein interacted with NKX2.5 protein and inhibited binding of NKX2.5 to the 5'-proximal promoter region of myocardin in CVPC-derived VSMCs. In conclusion, YAP negatively regulates differentiation of VSMCs from CVPCs by decreasing transcription of myocardin in a NKX2.5-dependent manner. Stem Cells 2017;35:351-361.

  19. 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.

  20. 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.)

  1. 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

  2. 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.

  3. Circulating progenitor cells in hypertensive subjects: Effectiveness of a treatment with olmesartan in improving cell number and miR profile in addition to expected pharmacological effects

    Science.gov (United States)

    Aragona, Caterina Oriana; Cairo, Valentina; Scuruchi, Michele; Lo Gullo, Alberto; D’Ascola, Angela; Alibrandi, Angela; Loddo, Saverio; Quartuccio, Sebastiano; Morace, Carmela; Mormina, Enricomaria; Basile, Giorgio; Saitta, Antonino; Imbalzano, Egidio

    2017-01-01

    CD34+ circulating progenitor cells (CD34+CPCs) are a population of multipotent cells which can delay the development of atherosclerosis and cardiovascular disease (CVD) in conditions of increased CV risk. MicroRNAs (miRs) 221 and 222 modulate different genes regulating angiogenesis and inflammation; moreover, miR221/22 have beenshown to participate in differentiation and proliferation of CD34+CPCs, inhibiting cell migration and homing. miR221/222 in CD34+CPCs from hypertensive subjects are also increased and associated with CD34+cell number and reactive oxygen species (ROS). We evaluated CD34+CPC number, intracellular miR221/222 and ROS levels, arterial stiffness (AS)and echocardiography indices at baseline (T0).Then, after a six-month treatment with olmesartan, 20 mg/day (T1), in 57 hypertensive patients with left ventricular hypertrophy (LVH) and with no additional risk factor for CVD, and in 29 healthy controls (baseline),fibrinogen, C-reactive protein (CRP), glucose and lipid profiles were also evaluated.At T1, blood pressure values, CRP and fibrinogen levels, ROS and miR221/222 were significantly decreased (all p <0.001), as were AS indices and LV mass index (p<0.001), while cell number was increased (p<0.001). Olmesartan is effective in reducing miR and ROS levels in CD34+CPCs from hypertensive subjects, as well as in increasing CD34+CPC number, providing multilevel CV protection, in addition to its expected pharmacological effects. PMID:28301500

  4. A vascular endothelial growth factor activating transcription factor increases the endothelial progenitor cells population and induces therapeutic angiogenesis in a type 1 diabetic mouse with hindlimb ischemia

    Institute of Scientific and Technical Information of China (English)

    Diao Yongpeng; Lian Lishan; Guo Lilong; Chen Houzao; Chen Yuexin; Song Xiaojun; Li Yongjun

    2014-01-01

    Background Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion.Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis.However,it has side effects that limit its therapeutic utility in vivo,especially at high concentrations.This study aimed to investigate whether an intramuscular injection of a genetically engineered zinc finger VEGF-activating transcription factor modulates the endothelial progenitor cells (EPC) and promotes therapeutic angiogenesis in a hindlimb ischemia model with type 1 diabetes.Methods Alloxan (intravenous injection) was used to induce type Ⅰ diabetes in C57BL/6 mice (n=58).The ischemic limb received ZFP-VEGF (125 μg ZFP-VEGF plasmid in 1% poloxamer) or placebo (1% poloxamer) intramuscularly.Mice were sacrificed 3,5,10,or 20 days post-injection.Limb blood flow was monitored using laser Doppler perfusion imaging.VEGF mRNA and protein expression were examined using real-time PCR and ELISA,respectively.Capillary density,proliferation,and apoptosis were examined using immunohistochemistry techniques.Flow cytometry was used to detect the EPC population in bone marrow.Two-tailed Student's paired t test and repeated-measures analysis of variance were used for statistical analysis.Results ZFP-VEGF increased VEGF mRNA and protein expression at 3 and 10 days post-injection,and increased EPC in bone marrow at day 5 and 20 post-injection compared with controls (P<0.05).ZFP-VEGF treatment resulted in better perfusion recovery,a higher capillary density and proliferation,and less apoptosis compared with controls (P<0.05).Conclusions Intramuscular ZFP-VEGF injection promotes therapeutic angiogenesis in an ischemic hindlimb model with type 1 diabetes.This might be due to the effects of VEGF on cell survival and EPC recruitment.

  5. 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.

  6. Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Kelly; Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Schnell, Susanne; Barker, Alex J.; Garcia, Julio; Chowdhary, Varun; Carr, James [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Lorenz, Ramona [University Medical Center Freiburg, Department of Radiology, Freiburg (Germany); Rose, Michael [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Robinson, Joshua D. [Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Cardiology, Chicago, IL (United States); Rigsby, Cynthia K. [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-10-15

    Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R{sup 2}=0.50, P=0.02; SVC to LPA: R{sup 2}=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability. (orig.)

  7. 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

  8. Study on the function of circulating endothelial progenitor cell in the patients with pregnancy induced hypertension syndrome%妊娠高血压综合征患者循环内皮祖细胞功能的研究

    Institute of Scientific and Technical Information of China (English)

    王莉莉; 黄军华; 刘俊峰; 温秋玉

    2013-01-01

    Objective To study the changes of circulating endothelial progenitor cell's function in the patients with pregnancy induced hypertension syndrome. Methods 12 patients suffered from pregnancy induced hypertension syndrome hospitalized in the department of obstetrics of our hospital from October 2010 to August 2011 were selected as study objects (pregnancy induced hypertension syndrome group),12 hospitalized normal pregnant women at the corresponding time period were selected as control group. The peripheral blood mononuclear cells were separated and cultured in vitro to obtain endothelial progenitor cells in each group. The abilities of endothelial progenitor cell' s proliferation,adhesion,migration were assessed. Results Endothelial progenitor cells could be attained from peripheral blood mononuclear cells when cultured in vitro in each group. The abilities of endothelial progenitor cell' s proliferation,adhesion,migration in the pregnancy induced hypertension syndrome group were down -regulation compared with the control group. Conclusion The occurrence of pregnancy induced hypertension syndrome is associated with the down-regulation of circulating endothelial progenitor cell's function evidently.%目的 研究妊娠高血压综合征患者循环内皮祖细胞功能的变化.方法 选择2010年10月~2011年8月于我院产科住院的妊娠高血压综合征患者12例作为研究对象(妊娠高血压综合征组),同时选取12例正常妊娠的同期入院患者作为对照组.分离两组患者外周血单个核细胞进行体外诱导培养以获得内皮祖细胞,并对其增殖、黏附、迁移能力进行检测.结果 各组骨髓单个核细胞在体外培养下均能够获得内皮祖细胞,与对照组比较,妊娠高血压综合征组内皮祖细胞增殖、黏附、迁移能力均有不同程度的下降.结论 妊娠高血压综合征的发生与循环内皮祖细胞功能的下调存在明显的相关性.

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

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    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.

  10. 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

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

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    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

  12. A pilot trial to examine the association between circulating endothelial cell levels and vascular injury in patients with diabetes and chronic kidney disease [version 1; referees: 2 approved

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    Shayan Shirazian

    2016-03-01

    Full Text Available Objective While albuminuria is a marker for progressive chronic kidney disease (CKD in patients with type 2 diabetes (T2DM, both albuminuric and normoalbuminuric patients appear prone to vascular injury. This pilot study examines the association between circulating endothelial cell (CEC levels and vascular injury in patients with T2DM and CKD. Methods In this cross-sectional study, eligible adult patients had T2DM, and stage 3 CKD (estimated glomerular filtration rate between 30 and 60 mL/min/1.73m2. CEC levels were tested by Janssen Diagnostics, LLC using an immuno-magnetic bead-based assay. CEC levels were compared to levels in a previously tested normal population. Correlations between CEC levels and other vascular injury markers (urine albumin, von-Willebrand factor antigen, hs-CRP, uric acid were performed. Results Patients included 40 adults of which nineteen were normoalbuminuric.  Mean CEC levels (38.7, SD 38.1 cells were significantly higher than the normal population (M = 21±18 cells, p<0.001; N = 249, including in the normoalbuminuric subgroup (M = 42.9±42.5 cells, p<0.001. CEC levels were significantly correlated with uric acid levels (r=0.33, p=0.039. Conclusions CEC levels in patients with T2DM and CKD, both albuminuric and normoalbuminuric, are significantly higher than a normal population, suggesting the presence of vascular injury in both groups. Future studies are needed to evaluate the role of CECs as a biomarker to predict outcomes in normoalbuminuric patients with CKD.

  13. 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.

  14. Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

    Science.gov (United States)

    Kilian, Yvonne; Wehmeier, Udo F.; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

    2016-01-01

    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 years; 57.9 ± 9.4 ml·min−1·kg−1 peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90–95% peak power output (PPO), 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% PPO. 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. PMID:27014090

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

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    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.

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

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    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.

  17. Circulating CD4(+)CD28null T Cells May Increase the Risk of an Atherosclerotic Vascular Event Shortly after Kidney Transplantation.

    Science.gov (United States)

    Betjes, Michiel G H; Weimar, Willem; Litjens, Nicolle H R

    2013-01-01

    Proinflammatory CD4(+) T cells without the costimulatory molecule CD28 (CD4(+)CD28null T cells) are expanded in patients with end-stage renal disease (ESRD) and associated with atherosclerotic vascular events (AVE). In a prospective study, the number of circulating CD4(+)CD28null T cells was established in 295 ESRD patients prior to receiving a kidney allograft. Within the first year after transplantation, an AVE occurred in 20 patients. Univariate analysis showed that besides a history of cardiovascular disease (CVDpos, HR 8.1, P AVE. In a multivariate analysis, only CVDpos remained a significant risk factor with a significant and positive interaction between the terms CVDpos and the % of CD4(+)CD28null T cells (HR 1.05, 95% CI 1.03-1.11, P AVE was 13% in the lowest tertile compared to 25% in the highest tertile of % of CD4(+)CD28null T cells. In conclusion, the presence of circulating CD4(+)CD28null T cells is associated with an increased risk for a cardiovascular event shortly after kidney transplantation.

  18. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    Science.gov (United States)

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  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. Prospective transcriptomic pathway analysis of human lymphatic vascular insufficiency: identification and validation of a circulating biomarker panel.

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    Shin Lin

    Full Text Available BACKGROUND: In our previous transcriptional profiling of a murine model, we have identified a remarkably small number of specific pathways with altered expression in lymphedema. In this investigation, we utilized microarray-based transcriptomics of human skin for an unbiased a priori prospective candidate identification, with subsequent validation of these candidates through direct serum assay. The resulting multi-analyte biomarker panel sensitively should sensitively discriminate human lymphedema subjects from normal individuals. METHODS AND FINDINGS: We enrolled 63 lymphedema subjects and 27 normals in our attempt to discover protein analytes that can distinguish diseased individuals from controls. To minimize technical and biologically irrelevant variation, we first identified potential candidates by performing transcriptional microarray analysis on paired diseased and normal skin specimens sampled from the same individuals. We focused our attention on genes with corresponding protein products that are secreted and took these candidates forward to a protein multiplex assay applied to diseased and normal subjects. We developed a logistic regression-based model on an eventual group of six proteins and validated our system on a separate cohort of study subjects. The area under the receiver operating characteristic curve was calculated to be 0.87 (95% CI : 0.75 to 0.97. CONCLUSIONS: We have developed an accurate bioassay utilizing proteins representing four central pathogenetic modalities of the disease: lymphangiogenesis, inflammation, fibrosis, and lipid metabolism, suggesting that these proteins are directly related to the pathogenesis of the tissue pathology in lymphatic vascular insufficiency. Further studies are warranted to determine whether this newly-identified biomarker panel will possess utility as an instrument for in vitro diagnosis of early and latent disease; the ultimate applicability to risk stratification, quantitation of

  2. Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study: time-course after acute myocardial infarction and stroke.

    Science.gov (United States)

    Regueiro, Ander; Cuadrado-Godia, Elisa; Bueno-Betí, Carlos; Diaz-Ricart, Maribel; Oliveras, Anna; Novella, Susana; Gené, Gemma González; Jung, Carole; Subirana, Isaac; Ortiz-Pérez, Jose Tomás; Roqué, Mercè; Freixa, Xavier; Núñez, Julio; Escolar, Gines; Marrugat, Jaume; Hermenegildo, Carlos; Valverde, Miguel Angel; Roquer, Jaume; Sanchis, Juan; Heras, Magda

    2015-03-01

    The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; pstroke patients, the number of endothelial progenitor cells - but not circulating endothelial cells - was higher than in controls (90.0/mL vs. 37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however, VCAM-1 peaked (628.1/mL vs. 869.1/mL; pafter stroke, circulating endothelial cells and VWF decreased, compared to baseline. Cultured endothelial progenitor cells from controls and myocardial infarction patients had endothelial phenotype characteristics and exhibited functional differences in adhesion and Ca(2+) influx, but not in proliferation and vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization of endothelial progenitor cells peaked at 30 days after the ischemic event. Although a similar VCAM-1 kinetic was observed in stroke patients

  3. 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

  4. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension.

    Science.gov (United States)

    Yang, Zhen; Chen, Long; Su, Chen; Xia, Wen-Hao; Wang, Yan; Wang, Jie-Mei; Chen, Fei; Zhang, Yuan-Yuan; Wu, Fang; Xu, Shi-Yue; Zhang, Xiao-Lin; Tao, Jun

    2010-01-01

    Endothelial dysfunction is related to reduced arterial elasticity in patients with essential hypertension. Circulating endothelial progenitor cells (EPCs), an important endogenous repair approach for endothelial injury, is altered in hypertensive patients. However, the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity has not been reported. The purpose of this study is to investigate the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity. We measured the artery elasticity profiles including brachial-ankle PWV (baPWV) and C1 large and C2 small artery elasticity indices in patients with essential hypertension (n = 20) and age-matched normotensive subjects (n = 21). The number and activity of circulating EPCs isolated from peripheral blood were determined. Compared to normotensive subjects, the patients with hypertension exhibited decreased C1 large and C2 small artery elasticity indices, as well as increased baPWV. The number of circulating EPCs did not differ between the two groups. The migratory and proliferative activities of circulating EPCs in hypertensive patients were lower than those in normotensive subjects. Both proliferatory and migratory activities of circulating EPCs closely correlated with arterial elasticity profiles, including baPWV and C1 large and C2 small artery elasticity indices. Multivariate analysis identified both proliferative and migratory activities of circulating EPCs as independent predictors of the artery elasticity profiles. The present study demonstrates for the first time that impaired activity of circulating EPCs is associated with reduced arterial elasticity in patients with hypertension. The fall in endogenous repair capacity of vascular endothelium may be involved in the pathogenesis of hypertension-related vascular injury.

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

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    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

  6. Aberrant lymphatic endothelial progenitors in lymphatic malformation development.

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    June K Wu

    Full Text Available Lymphatic malformations (LMs are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4, circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2, and lymphatic endothelial proteins (podoplanin, VEGFR-3. Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133- cells isolated from LM fluids. CD133- LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133- LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.

  7. Progenitor Cells for Arterial Repair: Incremental Advancements towards Therapeutic Reality

    Science.gov (United States)

    Simard, Trevor; Jung, Richard G.; Motazedian, Pouya; Di Santo, Pietro; Ramirez, F. Daniel; Russo, Juan J.; Labinaz, Alisha; Yousef, Altayyeb; Anantharam, Brijesh; Pourdjabbar, Ali

    2017-01-01

    Coronary revascularization remains the standard treatment for obstructive coronary artery disease and can be accomplished by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. Considerable advances have rendered PCI the most common form of revascularization and improved clinical outcomes. However, numerous challenges to modern PCI remain, namely, in-stent restenosis and stent thrombosis, underscoring the importance of understanding the vessel wall response to injury to identify targets for intervention. Among recent promising discoveries, endothelial progenitor cells (EPCs) have garnered considerable interest given an increasing appreciation of their role in vascular homeostasis and their ability to promote vascular repair after stent placement. Circulating EPC numbers have been inversely correlated with cardiovascular risk, while administration of EPCs in humans has demonstrated improved clinical outcomes. Despite these encouraging results, however, advancing EPCs as a therapeutic modality has been hampered by a fundamental roadblock: what constitutes an EPC? We review current definitions and sources of EPCs as well as the proposed mechanisms of EPC-mediated vascular repair. Additionally, we discuss the current state of EPCs as therapeutic agents, focusing on endogenous augmentation and transplantation. PMID:28232850

  8. Endothelial progenitor cells as a new marker of endothelial function with respect to risk of cardiovascular disorders

    Directory of Open Access Journals (Sweden)

    Barbara Głowińska-Olszewska

    2011-01-01

    Full Text Available The discovery of endothelial progenitor cells (EPC, over a decade ago, has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The results of several studies revealed altered number and impaired function of EPC in hyperlipidemia, hypertension, diabetes, obesity as well as in rheumatoid arthritis. The population of developmental age is characterized by higher counts of EPC compared to adults. However, among young patients with chronic disorders that affect the vascular system, the number of EPC decreases. The reduced circulating concentration of EPC has become a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases. This article aims to review the biology and pathophysiology of EPC in the conditions of cardiovascular risk factors. The potential possibilities of increasing EPC number and function as well as the use of EPC in the treatment of vascular pathology will also be discussed.

  9. 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

  10. 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.

  11. 乐卡地平治疗老年高血压及其对循环造血祖细胞的作用%Effect of Lecarnidipine on hypertension and circulation hematopoietic progenitor cells in the elderly

    Institute of Scientific and Technical Information of China (English)

    沈培晓; 汪海娅

    2015-01-01

    目的 探讨乐卡地平治疗老年高血压患者的疗效和对外周血造血祖细胞数量的影响.方法 入选上海交通大学医学院附属仁济医院老年科2014年1-12月门诊就诊的高血压患者61例,数字抽签随机分为乐卡地平组32例,服用盐酸乐卡地平5~10 mg/d;对照组29例,降压药物根据患者情况采用噻嗪类利尿剂和(或)β受体阻滞剂,观察12周,目标血压为< 140/90 mmHg(1mmHg=0.133 kPa).用药前后检测患者血脂、血糖、肝肾功能及红细胞沉降率等实验室检查指标,采用流式细胞分析的方法检测外周造血祖细胞数量(以外周血CD34+ CD45dim细胞的数量外周血100 000个单核细胞的百分比进行计数). 结果 乐卡地平组用药后血压下降,患者血压均达标.血压下降幅度对照组与乐卡地平组比较差异无统计学意义(P>0.05).乐卡地平治疗12周后CD34+ CD45dim细胞数升高(0.022±0.003)%与(0.034±0.028)% (P<0.05);与对照组比较,乐卡地平组CD34+ CD45dim细胞数量有上升趋势,但差异无统计学意义(P>0.05).以CD34+ CD45dim数量为自变量,行多元逐步线性回归分析结果显示,收缩压与CD34+ CD45dim细胞数量呈负相关(B=-1.794,t=-23.04,P<0.01). 结论 老年高血压患者外周血祖细胞数量与收缩压呈负相关.乐卡地平增加外周血祖细胞数量,且不依赖于其降压作用.%Objective To investigate the effect of Lecarnidipine on hypertension and circulation hematopoietic progenitor cells (HPCs) count in elderly patients.Methods A total of 61 elderly patients with hypertension were selected in Renji Hospital geriatric hypertension clinic from January 2014 to August 2014.Patients were randomly divided into two groups:Lercanidipine treatment group (n=32,Lercanidipine hydrochloride 5-10 mg/day),the control group (n=29,thiazide diuretics and / or beta blockers according to patient's condition).Patients were observed for 12 weeks,and the target blood pressure

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 活血化瘀法治疗急性脑血管病的效果评价%Effect and Evaluation in Treatment Acute Cerebro Vascular Disease of Blood Circulation

    Institute of Scientific and Technical Information of China (English)

    李雪

    2015-01-01

    目的:探讨活血化瘀法治疗急性脑血管病的临床疗效。方法选取我院接收的54例急性脑血管病患者作为本次的研究对象,所有患者均采用活血化瘀法进行治疗,并对其临床资料进行回顾性分析,对活血化瘀法在急性脑血管病中的应用效果进行评价分析。结果本组54例患者采用活血化瘀法治疗后痊愈28例,显效12例,有效10例,无效4例,治疗总有效率为92.59%,无效率为7.41%。结论给予急性脑血管疾病患者活血化瘀法治疗可取的较好的治疗效果。%Objective To investigate the clinical effect of activating blood and resolving stasis in treatment of acute cerebral vascular disease.MethodsChoose 54 cases of acute cerebral vascular disease patients in our hospital,al patients were treated by promoting blood circulation and removing blood stasis method treatment,and the clinical data were analyzed retrospectively,to evaluate the application effect of promoting blood circulation and removing blood stasis in patients with acute cerebrovascular disease.Results 54 patients in this group with promoting blood circulation and removing blood stasis after treatment,28 cases recovered,22 cases markedly effective,4 cases ineffective,the total effective rate was 92.59%,no effect in 7.41%.Conclusion Giving the better therapeutic effect in patients with acute cerebral vascular disease desirable and activating blood stasis treatment,the higher clinical value,should be popularized and applied.

  16. Vascular Cures

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation

    DEFF Research Database (Denmark)

    Vlachopoulos, Charalambos; Xaplanteris, Panagiotis; Aboyans, Victor

    2015-01-01

    While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a s...... superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required....

  19. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  20. 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.

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

    OpenAIRE

    2015-01-01

    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 p...

  2. The multiple personality disorder phenotype(s) of circulating endothelial cells in cancer.

    Science.gov (United States)

    Bertolini, Francesco; Mancuso, Patrizia; Braidotti, Paola; Shaked, Yuval; Kerbel, Robert S

    2009-08-01

    Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are currently being investigated in a variety of diseases as markers of vascular turnover or damage and, also in the case of CEPs, vasculogenesis. CEPs appear to have a "catalytic" role in different steps of cancer progression and recurrence after therapy, and there are preclinical and clinical data suggesting that CEC enumeration might be useful to select and stratify patients who are candidates for anti-angiogenic treatments. In some types of cancer, CECs and CEPs might be one of the possible hidden identities of cancer stem cells. The definition of CEC and CEP phenotype and the standardization of CEC and CEP enumeration strategies are highly desirable goals in order to exploit these cells as reliable biomarkers in oncology clinical trials.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. 兔骨髓源单个核细胞诱导血管内皮祖细胞修复尿道缺损%Bone marrow mononuclear cells-differentiated vascular endothelial progenitor cells for urethral defect repair in rabbits

    Institute of Scientific and Technical Information of China (English)

    张谦; 单岩; 李泸平; 范应中; 王家祥

    2008-01-01

    BACKGROUND: How to solve the source of material substitute for repair of urethral dcfoct and improve the blood supply of new urethra has become a critical problem in the urethral repair and reconstruction.OBJECTIVE: To investigate the effects of endothelial progenitor cells (EPCs) on improving blood circulation in the new urethra following urethral defect repair.DESIGN,TIME AND SETTING: In vivo tissue engineering experiment,performed at the Laboratory of Deparanent of Surgery,First Affiliated Hospital of Zhengzhou University between January 2006 and February 2008.MATERIALS: Thirteen 3-5-month-old male Japanese rabbits were included for this study.Of them,one was used for preparation of bone marrow mononuclear cells,and the remaining twelve rabbits were divided into EPC repair group (n=8) and model group (n=4).METHODS: Under the aseptic condition,bone marrow was taken from the rabbit bilateral anterior superior lilac spine.Mononuclear cells isolated by Percoll method were induced in vitro using medium supplemented with vascular endothelial growth factors (VEGFs) and bovine basic fihroblast growth factors.When covering the whole bottom of culture flask,the mononuclear cells were digested with trypsin for passage.Animal models of urethral defect were developed in the two groups.One piece of aseptic fresh acellular human amnion (1 cm2) was sutured to each defected urethra using 0/6 DG suture for forming urethra.In the EPC repair group,1010/L passage 3 rabbit bone marrow mononuclear cell suspension was injected to two anastomotic stomas of the new urethra,0.1 mL for each stoma.The subcutaneous tissue was interruptedly sutured to the formed urethra using 0/6 DG suture.In addition,0.5 mL bone marrow mononuclear cell suspension was added to the region between each anastomotic stroma and newly repaired urethra.The same procedure was performed in the model group except that bone marrow mononuclear cell suspension was replaced by cell-free medium.At weeks 4 and 12 after

  8. Endothelial progenitor cell-based neovascularization : implications for therapy

    NARCIS (Netherlands)

    Krenning, Guido; van Luyn, Marja J. A.; Harmsen, Martin C.

    2009-01-01

    Ischemic cardiovascular events are a major cause of death globally. Endothelial progenitor cell (EPC)-based approaches can result in improvement of vascular perfusion and might offer clinical benefit. However, although functional improvement is observed, the lack of long-term engraftment of EPCs int

  9. Loss of endothelial-ARNT in adult mice contributes to dampened circulating proangiogenic cells and delayed wound healing.

    Science.gov (United States)

    Han, Yu; Tao, Jiayi; Gomer, Alla; Ramirez-Bergeron, Diana L

    2014-12-01

    The recruitment and homing of circulating bone marrow-derived cells include endothelial progenitor cells (EPCs) that are critical to neovascularization and tissue regeneration of various vascular pathologies. We report here that conditional inactivation of hypoxia-inducible factor's (HIF) transcriptional activity in the endothelium of adult mice (Arnt(ΔiEC) mice) results in a disturbance of infiltrating cells, a hallmark of neoangiogenesis, during the early phases of wound healing. Cutaneous biopsy punches show distinct migration of CD31(+) cells into wounds of control mice by 36 hours. However, a significant decline in numbers of infiltrating cells with immature vascular markers, as well as decreased transcript levels of genes associated with their expression and recruitment, were identified in wounds of Arnt(ΔiEC) mice. Matrigel plug assays further confirmed neoangiogenic deficiencies alongside a reduction in numbers of proangiogenic progenitor cells from bone marrow and peripheral blood samples of recombinant vascular endothelial growth factor-treated Arnt(ΔiEC) mice. In addition to HIF's autocrine requirements in endothelial cells, our data implicate that extrinsic microenvironmental cues provided by endothelial HIF are pivotal for early migration of proangiogenic cells, including those involved in wound healing.

  10. 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

  11. Glycosaminoglycan mimetic improves enrichment and cell functions of human endothelial progenitor cell colonies.

    Science.gov (United States)

    Chevalier, Fabien; Lavergne, Mélanie; Negroni, Elisa; Ferratge, Ségolène; Carpentier, Gilles; Gilbert-Sirieix, Marie; Siñeriz, Fernando; Uzan, Georges; Albanese, Patricia

    2014-05-01

    Human circulating endothelial progenitor cells isolated from peripheral blood generate in culture cells with features of endothelial cells named late-outgrowth endothelial colony-forming cells (ECFC). In adult blood, ECFC display a constant quantitative and qualitative decline during life span. Even after expansion, it is difficult to reach the cell dose required for cell therapy of vascular diseases, thus limiting the clinical use of these cells. Glycosaminoglycans (GAG) are components from the extracellular matrix (ECM) that are able to interact and potentiate heparin binding growth factor (HBGF) activities. According to these relevant biological properties of GAG, we designed a GAG mimetic having the capacity to increase the yield of ECFC production from blood and to improve functionality of their endothelial outgrowth. We demonstrate that the addition of [OTR(4131)] mimetic during the isolation process of ECFC from Cord Blood induces a 3 fold increase in the number of colonies. Moreover, addition of [OTR(4131)] to cell culture media improves adhesion, proliferation, migration and self-renewal of ECFC. We provide evidence showing that GAG mimetics may have great interest for cell therapy applied to vascular regeneration therapy and represent an alternative to exogenous growth factor treatments to optimize potential therapeutic properties of ECFC.

  12. Endothelial Progenitor Cells in Tumor Angiogenesis: Another Brick in the Wall

    Directory of Open Access Journals (Sweden)

    Marina Marçola

    2015-01-01

    Full Text Available Until 15 years ago, vasculogenesis, the formation of new blood vessels from undifferentiated cells, was thought to occur only during embryonic development. The discovery of circulating cells that are able to promote vascular regeneration and repair—the so-called endothelial progenitor cells (EPCs—changed that, and EPCs have since been studied extensively. It is already known that EPCs include many subtypes of cells that play a variety of roles in promoting vascular growth. Some EPCs are destined to differentiate into endothelial cells, whereas others are capable of promoting and sustaining angiogenesis through paracrine mechanisms. Vasculogenesis and angiogenesis might constitute complementary mechanisms for postnatal neovascularization, and EPCs could be at the core of this process. Although the formation of new blood vessels from preexisting vasculature plays a beneficial role in many physiological processes, such as wound healing, it also contributes to tumor growth and metastasis. However, many aspects of the role played by EPCs in tumor angiogenesis remain unclear. This review aims to address the main aspects of EPCs differentiation and certain characteristics of their main function, especially in tumor angiogenesis, as well as the potential clinical applications.

  13. A comparison of the tube forming potentials of early and late endothelial progenitor cells.

    Science.gov (United States)

    Mukai, Nana; Akahori, Taichi; Komaki, Motohiro; Li, Qin; Kanayasu-Toyoda, Toshie; Ishii-Watabe, Akiko; Kobayashi, Akiko; Yamaguchi, Teruhide; Abe, Mayumi; Amagasa, Teruo; Morita, Ikuo

    2008-02-01

    The identification of circulating endothelial progenitor cells (EPCs) has revolutionized approaches to cell-based therapy for injured and ischemic tissues. However, the mechanisms by which EPCs promote the formation of new vessels remain unclear. In this study, we obtained early EPCs from human peripheral blood and late EPCs from umbilical cord blood. Human umbilical vascular endothelial cells (HUVECs) were also used. Cells were evaluated for their tube-forming potential using our novel in vitro assay system. Cells were seeded linearly along a 60 mum wide path generated by photolithographic methods. After cells had established a linear pattern on the substrate, they were transferred onto Matrigel. Late EPCs formed tubular structures similar to those of HUVECs, whereas early EPCs randomly migrated and failed to form tubular structures. Moreover, late EPCs participate in tubule formation with HUVECs. Interestingly, late EPCs in Matrigel migrated toward pre-existing tubular structures constructed by HUVECs, after which they were incorporated into the tubules. In contrast, early EPCs promote sprouting of HUVECs from tubular structures. The phenomena were also observed in the in vivo model. These observations suggest that early EPCs cause the disorganization of pre-existing vessels, whereas late EPCs constitute and orchestrate vascular tube formation.

  14. 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.

  15. Fetal Circulation

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Fetal Circulation Updated:Oct 18,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  16. 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

  17. 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.

  18. The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers

    Science.gov (United States)

    Mobarrez, Fariborz; Antoniewicz, Lukasz; Bosson, Jenny A.; Kuhl, Jeanette; Pisetsky, David S.; Lundbäck, Magnus

    2014-01-01

    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. PMID:24587320

  19. 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.

  20. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    Science.gov (United States)

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  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 SDF-1 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 SDF-1 expression was associated with number of circulating CD34(+) progenitor cells (r = 0.454, p SDF-1 and number of CD34(+) cells were higher in patients with DCM compared with patients with ICM (p SDF-1 and CD34(+) progenitor cells are especially increased in patients with severe impairment of left ventricular systolic function in CHF.

  2. Vascular Stem Cells in Vascular Remodeling and Diseases

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-12-01

    Full Text Available BACKGROUND: Blood vessels are a source of stem and progenitor cells, which likely contribute to a variety of vascular processes and diseases. Emerging concepts in this field could influence therapeutic approaches to diseases of blood vessels such as atherosclerosis. CONTENT: Vascular Stem Cells (VSCs field is only beginning to emerge, and thus, many issues regarding VSCs’s identity and function remain poorly understood. In fact, even after decades of intensive research, Mesenchymal Stem Cells (MSC, which is suggested to be VSCs, is still having many outstanding issues of its own. And, on top of this, likewise decades-long intensive pericyte research has not been able resolve the identity issue. While favors Adventitial Progenitor Cells (APCs over pericytes as the likely VSC candidate, it should be pointed out that currently the opposite view (i.e., pericytes as VSCs is more prevalent, and many excellent reviews, including a recent one, have discussed this issue extensively. SUMMARY: It has been postulated that, within the vasculature, APCs could differentiate into pericytes (CD34- CD31- CD140b+ SMA-, endothelial cells (CD34+ CD31+ CD140b- SMA-, and smooth muscle cells (SMCs (CD34- CD31- CD140b- SMA+; and during tissue expansion or repair, APCs could also differentiate into tissue-specific cell types (e.g., muscle and fat Thus, in vitro, APCs fulfill all criteria for being VSCs. Meanwhile, in vivo evidence is still limited and will require further investigation. KEYWORDS: vascular stem cells, VSC, mesenchymal stem cells, MSC, endothelial progenitor cells, EPC, adventitial progenitor cells, APC.

  3. 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.

  4. 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

  5. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.

    Science.gov (United States)

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P R

    2016-05-18

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P mobilization by G-CSF or AMD3100 was either increased or unaffected (P mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.

  6. 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。

  7. Endothelial progenitor cells: Exploring the pleiotropic effects of statins

    Science.gov (United States)

    Sandhu, Kully; Mamas, Mamas; Butler, Robert

    2017-01-01

    Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction, prior to any significant change in lipid profile. Therefore, pleiotropic mechanisms, other than lowering lipid profile alone, must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell (EPC) identification, role in vascular repair, factors affecting EPC numbers, the role of statins in current medical practice and their effects on EPC number. PMID:28163831

  8. 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

  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. 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.

  11. 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.

  12. [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

  13. Regulation of a vascular plexus by gata4 is mediated in zebrafish through the chemokine sdf1a.

    Directory of Open Access Journals (Sweden)

    Ingrid Torregroza

    Full Text Available Using the zebrafish model we describe a previously unrecognized requirement for the transcription factor gata4 controlling embryonic angiogenesis. The development of a vascular plexus in the embryonic tail, the caudal hematopoietic tissue (CHT, fails in embryos depleted of gata4. Rather than forming a normal vascular plexus, the CHT of gata4 morphants remains fused, and cells in the CHT express high levels of osteogenic markers ssp1 and runx1. Definitive progenitors emerge from the hemogenic aortic endothelium, but fail to colonize the poorly vascularized CHT. We also found abnormal patterns and levels for the chemokine sdf1a in gata4 morphants, which was found to be functionally relevant, since the embryos also show defects in development of the lateral line, a mechano-sensory organ system highly dependent on a gradient of sdf1a levels. Reduction of sdf1a levels was sufficient to rescue lateral line development, circulation, and CHT morphology. The result was surprising since neither gata4 nor sdf1a is obviously expressed in the CHT. Therefore, we generated transgenic fish that conditionally express a dominant-negative gata4 isoform, and determined that gata4 function is required during gastrulation, when it is co-expressed with sdf1a in lateral mesoderm. Our study shows that the gata4 gene regulates sdf1a levels during early embryogenesis, which impacts embryonic patterning and subsequently the development of the caudal vascular plexus.

  14. 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

  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. Serum-Free Generation of Multipotent Mesoderm (Kdr-positive) Progenitor Cells in Mouse Embryonic Stem Cells For Functional Genomics Screening

    OpenAIRE

    2012-01-01

    This unit describes a robust protocol for producing multipotent Kdr-expressing mesoderm progenitor cells in serum-free conditions and functional genomics screening using these cells. Kdr-positive cells are known to be able to differentiate into a wide array of mesoderm derivatives including, vascular endothelial cells, cardiomyocytes, hematopietic progenitors and smooth muscle cells. The efficient generation of such progenitor cells is of particular interest because it permits subsequent step...

  18. Bone marrow-derived progenitor cells augment venous remodeling in a mouse dorsal skinfold chamber model.

    Directory of Open Access Journals (Sweden)

    Megan E Doyle

    Full Text Available The delivery of bone marrow-derived cells (BMDCs has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM and Lin(-/Sca-1(+ progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1(+ progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1(+ progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif ligand 2 (CXCL2 and interferon gamma (IFNγ that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, and platelet derived growth factor-BB (PDGF-BB compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45(+ leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1(+ progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment.

  19. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  20. 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.

  1. 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).

  2. 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

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xin; Deng, Jinchuan; Yuan, Shuheng; Wang, Juan; Luo, Rifang; Chen, Si [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Jin, E-mail: jinxxwang@263.net [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Huang, Nan [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2016-11-15

    Highlights: • The dopamine/PEI film with controlled amine density was successfully prepared. • The DNA aptamer was assembled onto the film via electrostatic incorporation. • The A@DPfilmscanspecificallyandeffectivelycaptureEPCs. • The A@DP film can support the survival of ECs, control the hyperplasia of SMCs. • The dynamic/co-culture models are useful for studying cells competitive adhesion. - Abstract: 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.

  5. Endothelial progenitor cells in systemic sclerosis: their possible role in angiogenesis

    Directory of Open Access Journals (Sweden)

    N. Fracchiolla

    2011-09-01

    Full Text Available Background: Recently, several studies have demonstrated the presence of circulating endothelial progenitors (CEPs responsable for angiogenesis. Notably, these cells are able to migrate to ischemic tissues and differentiate in situ in mature endothelial cells. Aim of this study was to assess the presence of CEPs in the peripheral blood of patients with Sistemic Sclerosis (SSc and evaluate their significance as an attempt of re-vascularization Material and methods: Samples of peripheral blood from 40 healthy subjects and 56 patients with SSc were studied. Five-parameter, 3-color flow cytometry was performed with a FACScan. CEPs were defined as CD45 negative, CD34 and CD133 positive. In addition, plasma levels of vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF were detected by commercial ELISA (R&D Systems. Results: Levels of CEPs (CD133+/CD34+/CD45- were significantly higher in patients with SSc in comparison to HC (P = 0.01. No correlation was found between CEPs and any clinical parameter of disease neither activity score. CEPs were significantly higher in the group of patients with early disease, while their number decreased in the late phases of disease. Plasma levels of VEGF, but not bFGF, were significantly higher in SSc in comparison to HC (P<0.001 but no correlation was found between VEGF concentrations and CEP number. Conclusions: The presence of CEPs in patients with SSc suggest that sclerodermic hypoxic tissues could induce the mobilization of bone-marrow derived cells in an attempt to provided new vessels, in the early phase of the disease, at least.

  6. 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.

  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. Endothelial progenitor cells as a new cardiovascular risk factor in Klinefelter's syndrome.

    Science.gov (United States)

    Di Mambro, A; Ferlin, A; De Toni, L; Selice, R; Caretta, N; Foresta, C

    2010-06-01

    Klinefelter syndrome (KS) is associated with a significant reduced life expectancy (2.1 years) including greater mortality from cardiovascular diseases. Underlying causes that may involve low levels of testosterone as well as the extra X chromosome are not fully understood. Low testosterone may have a direct affect on vascular tissue or act indirectly via metabolic effects. Testosterone levels may act genomically on cardiac function via the androgen receptor (AR) or non-genomically. Recently, it has been demonstrated that a reduced number of circulating endothelial progenitor cells (EPCs) is an independent predictor of morbidity and mortality from cardiovascular diseases. Because EPCs have never been studied in KS, we evaluated the number of circulating EPCs in 68 adult 47,XXY Klinefelter men and 46 healthy males. Patients and controls were divided into two groups, according to the absence or presence of cardiovascular risk factors (CRFs). Controls without CRFs had significantly higher levels of EPCs than controls with CRFs; on the contrary, KS patients without CRFs had EPCs levels similar to KS men with risk factors and significantly lower with respect to controls without CRFs. The number of EPCs in patients with hypogonadism was not different from that of those with normal testosterone levels. Twenty-two hypogonadal patients were re-evaluated after 6 months of androgen therapy, but we did not observe any modification in the number of EPCs. These primary hypothesis-generating data suggest that factors involved in KS, whether hypogonadism, CRFs or other genetically determined factors related to the supernumerary X chromosome might contribute to a reduction in EPCs number and that this could be considered another CRF contributing to the increased mortality of these subjects.

  9. 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

    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) treate...

  10. 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.

  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. 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...

  13. 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...

  14. Ischemic preconditioning increases endothelial progenitor cell number to attenuate partial nephrectomy-induced ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Hao Liu

    Full Text Available OBJECTIVES: The objective of this study was to investigate the role of endothelial progenitor cells (EPCs in the modulation of ischemia-reperfusion injury (IRI in a partial nephrectomy (PN rat model using early-phase ischemic preconditioning (IPC. MATERIALS AND METHODS: Ninety male Sprague-Dawley rats were randomly divided into three groups following right-side nephrectomy: Sham-operated rats (surgery without vascular clamping; PN rats (renal blood vessels were clamped for 40 min and PN was performed; and IPC rats (pretreated with 15 min ischemia and 10 min reperfusion. At 1, 3, 6, 12, 24 h, and 3 days after reperfusion, the pool of circulating EPCs and kidneys were harvested. The extent of renal injury was assessed, along with EPC number, cell proliferation, angiogenesis, and vascular growth factor expression. RESULTS: Pretreated rats exhibited significant improvements in renal function and morphology. EPC numbers in the kidneys were increased at 12 h following reperfusion in the IPC group as compared to the PN or Sham groups. Cell proliferation (including endothelial and tubular epithelial cells and angiogenesis in peritubular capillaries were markedly increased in kidneys treated with IPC. In addition, vascular endothelial growth factor-A (VEGF-A and stromal cell-derived factor-1α (SDF-1α expression in the kidneys of pretreated rats was increased compared to rats subjected to PN. CONCLUSIONS: OUR INVESTIGATION SUGGESTED THAT: (1 the early phase of IPC may attenuate renal IRI induced by PN; (2 EPCs play an important role in renal protection, involving promotion of cell proliferation and angiogenesis through release of several angiogenic factors.

  15. 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.

  16. 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.

  17. 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

  18. Vascular Disease Foundation

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  19. What Is Vascular Disease?

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  20. 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.

  1. 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.

  2. 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

  3. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  4. 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.

  5. Effects of erythropoietin on advanced pulmonary vascular remodelling

    NARCIS (Netherlands)

    van Albada, M. E.; Sarvaas, G. J. du Marchie; Koster, J.; Houwertjes, M. C.; Berger, R. M. F.; Schoemaker, R. G.

    2008-01-01

    Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult ma

  6. Effect of Reishi polysaccharides on human stem/progenitor cells.

    Science.gov (United States)

    Chen, Wan-Yu; Yang, Wen-Bin; Wong, Chi-Huey; Shih, Daniel Tzu-Bi

    2010-12-15

    The polysaccharide fraction of Ganoderma lucidum (F3) was found to benefit our health in many ways by influencing the activity of tissue stem/progenitor cells. In this study, F3 was found to promote the adipose tissue MSCs' aggregation and chondrosphere formation, with the increase of CAM (N-CAM, I-CAM) expressions and autokine (BMP-2, IL-11, and aggrecan) secretions, in an in vitro chondrogenesis assay. In a stem cell expansion culture, it possesses the thrombopoietin (TPO) and GM-CSF like functions to enhance the survival/renewal abilities of primitive hematopoietic stem/progenitor cells (HSCs). F3 was found to promote the dendrite growth of blood mononuclear cells (MNCs) and the expression of cell adhesion molecules in the formation of immature dendritic cells (DC). On the other hand, F3 exhibited inhibitory effects on blood endothelial progenitor (EPC) colony formation, with concomitant reduction of cell surface endoglin (CD105) and vascular endothelial growth factor receptor-3 (VEGFR-3) marker expressions, in the presence of angiogenic factors. A further cytokine array analysis revealed that F3 indeed inhibited the angiogenin synthesis and enhanced IL-1, MCP-1, MIP-1, RANTES, and GRO productions in the blood EPC derivation culture. Collectively, we have demonstrated that the polysaccharide fraction of G. lucidum F3 exhibits cytokine and chemokine like functions which are beneficial to human tissue stem/progenitor cells by modulating their CAM expressions and biological activities. These findings provide us a better the observation that F3 glycopolysaccharides indeed possesses anti-angiogenic and immune-modulating functions and promotes hematopoietic stem/progenitor cell homing for better human tissue protection, reducing disease progression and health.

  7. 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

  8. 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.

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

    Science.gov (United States)

    Appleby, Sarah L; Cockshell, Michaelia P; Pippal, Jyotsna B; Thompson, Emma J; Barrett, Jeffrey M; Tooley, Katie; Sen, Shaundeep; Sun, Wai Yan; Grose, Randall; Nicholson, Ian; Levina, Vitalina; Cooke, Ira; Talbo, Gert; 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(+) 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.

  10. Cereral Circulation in Preeclampsia

    Directory of Open Access Journals (Sweden)

    A. A. Ivshin

    2008-01-01

    Full Text Available Objective: to evaluate the possibilities of using transcranial Doppler study in pregnant women and pueperas with preeclamp-sia. Subjects and methods. Two hundred and thirty-two pregnant women diagnosed as having varying preeclampsia were prospectively studied. A comparison group comprised 90 apparently healthy women in the third trimester of pregnancy. All the respondents underwent transcranial duplex scanning of the medial cerebral artery with the linear velocity values being determined. A number of the values reflecting the level of perfusion and intracranial pressures, hydrodynamic resistance in the system, cerebrovascular responsiveness and the state of the vascular wall were calculated. Correlation analysis was made between the parameters of cerebral circulation and the severity of preeclampsia, proteinuria, the severity of hydrops, and the parameters of central and peripheral hemodynamics. Results. The findings suggest that there is impaired cerebral perfusion in pregnant women and puerperas with varying preeclampsia, the severity of cerebral circulatory disorders being in proportion with that of preeclampsia. There is a close correlation between cerebral circulation and the individual criteria determining the severity of preeclampsia. The linear values of the Doppler spectrum, namely linear flow characteristics, are prognos-tically most significant. Conclusion. The introduction of transcranial Doppler study into obstetric care has permitted the authors not only to study cerebral circulatory disorders in healthy and pregnant women and puerperas with preeclampia in detail, but also to establish a number of highly significant prognostic criteria for the severity of this life-threatening complication of gestation. The results of transcranial Doppler study assist practitioners in timely and accurately solving the problems in the diagnosis of preeclampsia and in evaluating its severity. Cerebral circulatory values may be successfully used to

  11. Circulating Fibronectin Controls Tumor Growth

    Directory of Open Access Journals (Sweden)

    Anja von Au

    2013-08-01

    Full Text Available Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.

  12. 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.

  13. 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

  14. Circulation economics

    DEFF Research Database (Denmark)

    Ingebrigtsen, Stig; Jakobsen, Ove

    2006-01-01

    Purpose - This paper is an attempt to advance the critical discussion regarding environmental and societal responsibility in economics and business. Design/methodology/approach - The paper presents and discusses as a holistic, organic perspective enabling innovative solutions to challenges...... concerning the responsible and efficient use of natural resources and the constructive interplay with culture. To reach the goal of sustainable development, the paper argues that it is necessary to make changes in several dimensions in mainstream economics. This change of perspective is called a turn towards...... 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...

  15. Vascular dysfunction in preeclampsia.

    Science.gov (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

    2014-01-01

    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review.

  16. 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.

  17. Isolation of Human Fetal Liver Progenitors and Their Enhanced Proliferation by Three-Dimensional Coculture with Endothelial Cells

    Science.gov (United States)

    Xiong, Anming; Austin, Timothy W.; Lagasse, Eric; Uchida, Nobuko; Tamaki, Stanley; Bordier, Bruno B.; Weissman, Irving L.; Glenn, Jeffrey S.; Millan, Maria T.

    2008-01-01

    Liver progenitor cells, characterized by the coexpression of biliary and hepatocyte lineage markers and the ability to form colonies in culture, were isolated by flow cytometry from primary human fetal livers. These prospectively isolated liver progenitor cells supported hepatitis D virus infection, expressed, and produced albumin and α-fetoprotein, as tracked by albumin-and α-fetoprotein–driven lentiviral promoter reporter constructs and measured by ELISA, respectively. Coculture in three-dimensional (3D) fibrin gel with endothelial cells resulted in the formation of vascular structures by the endothelial cells and increased proliferation of liver progenitors. The enhanced proliferation of liver progenitors that was observed when liver progenitors and endothelial cells were cultured in direct contact was not achieved when liver progenitors and endothelial cells were cultured on adjacent but separate matrices and when they were cultured across transwell membranes. In conclusion, coculture of liver progenitors and endothelial cells in three-dimensional matrix resulted in enhanced liver progenitor proliferation and function. This coculture methodology offers a novel coculture system that could be applied for the development of engineered liver tissues. PMID:19230124

  18. 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...

  19. 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

    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...... 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......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...

  20. Directing migration of endothelial progenitor cells with applied DC electric fields.

    Science.gov (United States)

    Zhao, Zhiqiang; Qin, Lu; Reid, Brian; Pu, Jin; Hara, Takahiko; Zhao, Min

    2012-01-01

    Naturally-occurring, endogenous electric fields (EFs) have been detected at skin wounds, damaged tissue sites and vasculature. Applied EFs guide migration of many types of cells, including endothelial cells to migrate directionally. Homing of endothelial progenitor cells (EPCs) to an injury site is important for repair of vasculature and also for angiogenesis. However, it has not been reported whether EPCs respond to applied EFs. Aiming to explore the possibility to use electric stimulation to regulate the progenitor cells and angiogenesis, we tested the effects of direct-current (DC) EFs on EPCs. We first used immunofluorescence to confirm the expression of endothelial progenitor markers in three lines of EPCs. We then cultured the progenitor cells in EFs. Using time-lapse video microscopy, we demonstrated that an applied DC EF directs migration of the EPCs toward the cathode. The progenitor cells also align and elongate in an EF. Inhibition of vascular endothelial growth factor (VEGF) receptor signaling completely abolished the EF-induced directional migration of the progenitor cells. We conclude that EFs are an effective signal that guides EPC migration through VEGF receptor signaling in vitro. Applied EFs may be used to control behaviors of EPCs in tissue engineering, in homing of EPCs to wounds and to an injury site in the vasculature.

  1. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  2. 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.

  3. 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.

  4. The poster as modernist progenitor

    OpenAIRE

    Katherine Hauser

    2015-01-01

    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.

  5. Gamma-ray burst progenitors

    CERN Document Server

    Levan, Andrew; de Grijs, Richard; Langer, Norbert; Xu, Dong; Yoon, Sung-Chul

    2016-01-01

    We review our current understanding of the progenitors of both long and short duration gamma-ray bursts (GRBs). Constraints can be derived from multiple directions, and we use three distinct strands; i) direct observations of GRBs and their host galaxies, ii) parameters derived from modeling, both via population synthesis and direct numerical simulation and iii) our understanding of plausible analog progenitor systems observed in the local Universe. From these joint constraints, we describe the likely routes that can drive massive stars to the creation of long GRBs, and our best estimates of the scenarios that can create compact object binaries which will ultimately form short GRBs, as well as the associated rates of both long and short GRBs. We further discuss how different the progenitors may be in the case of black hole engine or millisecond-magnetar models for the production of GRBs, and how central engines may provide a unifying theme between many classes of extremely luminous transient, from luminous an...

  6. Gamma-Ray Burst Progenitors

    Science.gov (United States)

    Levan, Andrew; Crowther, Paul; de Grijs, Richard; Langer, Norbert; Xu, Dong; Yoon, Sung-Chul

    2016-12-01

    We review our current understanding of the progenitors of both long and short duration gamma-ray bursts (GRBs). Constraints can be derived from multiple directions, and we use three distinct strands; (i) direct observations of GRBs and their host galaxies, (ii) parameters derived from modelling, both via population synthesis and direct numerical simulation and (iii) our understanding of plausible analog progenitor systems observed in the local Universe. From these joint constraints, we describe the likely routes that can drive massive stars to the creation of long GRBs, and our best estimates of the scenarios that can create compact object binaries which will ultimately form short GRBs, as well as the associated rates of both long and short GRBs. We further discuss how different the progenitors may be in the case of black hole engine or millisecond-magnetar models for the production of GRBs, and how central engines may provide a unifying theme between many classes of extremely luminous transient, from luminous and super-luminous supernovae to long and short GRBs.

  7. 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.

  8. Intestinal circulation during inhalation anesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  9. 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

  10. Mobilization of endothelial progenitors by recurrent bacteremias with a periodontal pathogen.

    Directory of Open Access Journals (Sweden)

    Moritz Kebschull

    Full Text Available BACKGROUND: Periodontal infections are independent risk factors for atherosclerosis. However, the exact mechanisms underlying this link are yet unclear. Here, we evaluate the in vivo effects of bacteremia with a periodontal pathogen on endothelial progenitors, bone marrow-derived cells capable of endothelial regeneration, and delineate the critical pathways for these effects. METHODS: 12-week old C57bl6 wildtype or toll-like receptor (TLR-2 deficient mice were repeatedly intravenously challenged with 10⁹ live P. gingivalis 381 or vehicle. Numbers of Sca1+/flk1+ progenitors, circulating angiogenic cells, CFU-Hill, and late-outgrowth EPC were measured by FACS/culture. Endothelial function was assessed using isolated organ baths, reendothelization was measured in a carotid injury model. RANKL/osteoprotegerin levels were assessed by ELISA/qPCR. RESULTS: In wildtype mice challenged with intravenous P.gingivalis, numbers of Sca1+/flk1+ progenitors, CAC, CFU-Hill, and late-outgrowth EPC were strongly increased in peripheral circulation and spleen, whereas Sca1+/flk1+ progenitor numbers in bone marrow decreased. Circulating EPCs were functional, as indicated by improved endothelial function and improved reendothelization in infected mice. The osteoprotegerin/RANKL ratio was increased after P. gingivalis challenge in the bone marrow niche of wildtype mice and late-outgrowth EPC in vitro. Conversely, in mice deficient in TLR2, no increase in progenitor mobilization or osteoprotegerin/RANKL ratio was detected. CONCLUSION: Recurrent transient bacteremias, a feature of periodontitis, increase peripheral EPC counts and decrease EPC pools in the bone marrow, thereby possibly reducing overall endothelial regeneration capacity, conceivably explaining pro-atherogenic properties of periodontal infections. These effects are seemingly mediated by toll-like receptor (TLR-2.

  11. Congenital cardiovascular malformations and the fetal circulation.

    Science.gov (United States)

    Rudolph, A M

    2010-03-01

    After birth, gas exchange is achieved in the lung, whereas prenatally it occurs in the placenta. This is associated with differences in blood flow patterns in the fetus as compared with the postnatal circulation. Congenital cardiovascular malformations are associated with haemodynamic changes in the fetus, which differ from those occurring postnatally. Obstruction to cardiac outflow may alter myocardial development, resulting in progressive ventricular hypoplasia. Alteration of oxygen content may profoundly influence pulmonary vascular and ductus arteriosus responses. Interference in blood flow and oxygen content may affect cerebral development as a result of inadequate oxygen or energy substrate supply. The circulatory effects may be gestational dependent, related to maturation of vascular responses in different organs. These prenatal influences of congenital cardiac defects may severely affect immediate, as well as longterm, postnatal prognosis and survival. This has stimulated the development of techniques for palliation of disturbed circulation during fetal life.

  12. Statins, HMG-CoA Reductase Inhibitors, Improve Neovascularization by Increasing the Expression Density of CXCR4 in Endothelial Progenitor Cells.

    Science.gov (United States)

    Chiang, Kuang-Hsing; Cheng, Wan-Li; Shih, Chun-Ming; Lin, Yi-Wen; Tsao, Nai-Wen; Kao, Yung-Ta; Lin, Chih-Ting; Wu, Shinn-Chih; Huang, Chun-Yao; Lin, Feng-Yen

    2015-01-01

    Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are used to reduce cholesterol biosynthesis in the liver. Accordingly, statins regulate nitric oxide (NO) and glutamate metabolism, inflammation, angiogenesis, immunity and endothelial progenitor cells (EPCs) functions. The function of EPCs are regulated by stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β), etc. Even though the pharmacologic mechanisms by which statins affect the neovasculogenesis of circulating EPCs, it is still unknown whether statins affect the EPCs function through the regulation of CXCR4, a SDF-1 receptor expression. Therefore, we desired to explore the effects of statins on CXCR4 expression in EPC-mediated neovascularization by in vitro and in vivo analyses. In animal studies, we analyzed the effects of atorvastatin or rosuvastatin treatments in recovery of capillary density and blood flow, the expression of vWF and CXCR4 at ischemia sites in hindlimb ischemia ICR mice. Additionally, we analyzed whether the atorvastatin or rosuvastatin treatments increased the mobilization, homing, and CXCR4 expression of EPCs in hindlimb ischemia ICR mice that underwent bone marrow transplantation. The results indicated that statins treatment led to significantly more CXCR4-positive endothelial progenitor cells incorporated into ischemic sites and in the blood compared with control mice. In vivo, we isolated human EPCs and analyzed the effect of statins treatment on the vasculogenic ability of EPCs and the expression of CXCR4. Compared with the control groups, the neovascularization ability of EPCs was significantly improved in the atorvastatin or rosuvastatin group; this improvement was dependent on CXCR4 up-regulation. The efficacy of statins on improving EPC neovascularization was related to the SDF-1α/CXCR4 axis and might be regulated by the NO. In conclusion, atorvastatin and rosuvastatin improved

  13. Endothelial Progenitor Cell Dysfunction in Polycystic Ovary Syndrome: Implications for The Genesis of Cardiovascular Diseases

    OpenAIRE

    Yu-Hsun Kao; Wan-Chun Chiu; Ming-I Hsu; Yi-Jen Chen

    2013-01-01

    Polycystic ovary syndrome (PCOS), the most common endocrine disorder affecting women of reproductive age, is characterized by hyperandrogenism and insulin resistance. Women with PCOS have a higher risk for cardiovascular diseases (CVDs) and endothelial dysfunction. The mechanisms underlying these risks are unclear. Human peripheral blood contains circulating endothelial progenitor cells (EPCs) derived from bone marrow that have the ability to proliferate and differentiate into mature endothel...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Targeting heme oxygenase-1 in vascular disease.

    Science.gov (United States)

    Durante, William

    2010-12-01

    Heme oxygenase-1 (HO-1) metabolizes heme to generate carbon monoxide (CO), biliverdin, and iron. Biliverdin is subsequently metabolized to bilirubin by biliverdin reductase. HO-1 has recently emerged as a promising therapeutic target in the treatment of vascular disease. Pharmacological induction or gene transfer of HO-1 ameliorates vascular dysfunction in animal models of atherosclerosis, post-angioplasty restenosis, vein graft stenosis, thrombosis, myocardial infarction, and hypertension, while inhibition of HO-1 activity or gene deletion exacerbates these disorders. The vasoprotection afforded by HO-1 is largely attributable to its end products: CO and the bile pigments, biliverdin and bilirubin. These end products exert potent anti-inflammatory, antioxidant, anti-apoptotic, and anti-thrombotic actions. In addition, CO and bile pigments act to preserve vascular homeostasis at sites of arterial injury by influencing the proliferation, migration, and adhesion of vascular smooth muscle cells, endothelial cells, endothelial progenitor cells, or leukocytes. Several strategies are currently being developed to target HO-1 in vascular disease. Pharmacological induction of HO-1 by heme derivatives, dietary antioxidants, or currently available drugs, is a promising near-term approach, while HO-1 gene delivery is a long-term therapeutic goal. Direct administration of CO via inhalation or through the use of CO-releasing molecules and/or CO-sensitizing agents provides an attractive alternative approach in targeting HO-1. Furthermore, delivery of bile pigments, either alone or in combination with CO, presents another avenue for protecting against vascular disease. Since HO-1 and its products are potentially toxic, a major challenge will be to devise clinically effective therapeutic modalities that target HO-1 without causing any adverse effects.

  19. [Fetal circulation in normal pregnancy and in placental insufficiency].

    Science.gov (United States)

    Ivanov, B; Malinova, M

    2010-01-01

    The fetal circulation is different from the adult circulation. One of the quite common conditions that are challenging to the developing fetus is placental hypoxia. Regardless of its cause, placental vascular insufficiency is commonly assumed to be an important factor in the development of intrauterine growth retardation. Several mechanisms are involved in the fetal adaptation to the decompensation during hypoxemia. Doppler Ultrasound technologies can help to evaluate of the fetal wellbeing.

  20. Society for Vascular Medicine

    Science.gov (United States)

    ... Certification with this new online course from the Society for Vascular Medicine. Learn more. Looking for a ... jobs are listed right now. Copyright © 2016 The Society for Vascular Medicine. All Rights Reserved.

  1. Interface dynamos in supernova progenitors

    CERN Document Server

    Blackman, E G; Thomas, J H; Blackman, Eric G.; Nordhaus, Jason T.; Thomas, John H.

    2004-01-01

    Observational evidence for anisotropy in supernovae (SN) and their phenomenological connection to jetted sources such as gamma-ray bursts^Mhave revived considerations of the role magnetohydrodynamic outflows might play therein. Understanding the types of dynamos that might operate in supernova progenitors is therefore relevant. In contrast to previous work, here we study an ``interface dynamo'' for the conditions of a rapidly rotating neutron star surrounded by a convective envelope. Such dynamos have been studied for the Sun, naked white dwarfs,and post-AGB stars, where analogous configurations of strong shear layers surrounded by convective envelopes are present. The interface dynamo provides estimates of large-scale poloidal and toroidal fields, whose product enters the Poynting flux. Because the poloidal field is much weaker than the toroidal magnetic field, the actual average Poynting flux is lower than rough estimates which invoke the only the magnitude of the total magnetic energy. The lower value is s...

  2. Progenitors of Supernovae Type Ia

    CERN Document Server

    Toonen, S; Bours, M; Zwart, S Portegies; Claeys, J; Mennekens, N; Ruiter, A

    2013-01-01

    Despite the significance of Type Ia supernovae (SNeIa) in many fields in astrophysics, SNeIa lack a theoretical explanation. The standard scenarios involve thermonuclear explosions of carbon/oxygen white dwarfs approaching the Chandrasekhar mass; either by accretion from a companion or by a merger of two white dwarfs. We investigate the contribution from both channels to the SNIa rate with the binary population synthesis (BPS) code SeBa in order to constrain binary processes such as the mass retention efficiency of WD accretion and common envelope evolution. We determine the theoretical rates and delay time distribution of SNIa progenitors and in particular study how assumptions affect the predicted rates.

  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. 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

  5. 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

  6. Establishment of an Early Vascular Network Promotes the Formation of Ectopic Bone

    NARCIS (Netherlands)

    Eman, Rhandy M.; Meijer, Henriette A W; Öner, F. Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

    2016-01-01

    Vascularization is crucial for the induction of bone formation. In this study, we investigated the application of two subtypes of peripheral blood-derived endothelial progenitor cells (EPCs) to stimulate vessel formation in ectopic bone constructs. Early and late outgrowth EPCs (E-EPC and L-EPC, res

  7. 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.

  8. Norepinephrine stimulates mobilization of endothelial progenitor cells after limb ischemia.

    Directory of Open Access Journals (Sweden)

    Qijun Jiang

    Full Text Available OBJECTIVE: During several pathological processes such as cancer progression, thermal injury, wound healing and hindlimb ischemia, the mobilization of endothelial progenitor cells (EPCs mobilization was enhanced with an increase of sympathetic nerve activity and norepinephrine (NE secretion, yet the cellular and molecular mechanisms involved in the effects of NE on EPCs has less been investigated. METHODS AND RESULTS: EPCs from BMs, peripheral circulation and spleens, the VEGF concentration in BM, skeletal muscle, peripheral circulation and spleen and angiogenesis in ischemic gastrocnemius were quantified in mice with hindlimbs ischemia. Systemic treatment of NE significantly increased EPCs number in BM, peripheral circulation and spleen, VEGF concentration in BM and skeletal muscle and angiogenesis in ischemic gastrocnemius in mice with hind limb ischemia, but did not affair VEGF concentration in peripheral circulation and spleen. EPCs isolated from healthy adults were cultured with NE in vitro to evaluate proliferation potential, migration capacity and phosphorylations of Akt and eNOS signal moleculars. Treatment of NE induced a significant increase in number of EPCs in the S-phase in a dose-dependent manner, as well as migrative activity of EPCs in vitro (p<0.05. The co-treatment of Phentolamine, I127, LY294002 and L-NAME with NE blocked the effects of NE on EPCs proliferation and migration. Treatment with NE significantly increased phosphorylation of Akt and eNOS of EPCs. Addition of phentolamine and I127 attenuated the activation of Akt/eNOS pathway, but metoprolol could not. Pretreatment of mice with either Phentolamine or I127 significantly attenuated the effects of NE on EPCs in vivo, VEGF concentration in BM, skeletal muscle and angiogenesis in ischemic gastrocnemius, but Metoprolol did not. CONCLUSION: These results unravel that sympathetic nervous system regulate EPCs mobilization and their pro-angiogenic capacity via α adrenoceptor

  9. 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

  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. 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.

  12. 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.

  13. 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...

  14. Hematopoietic progenitor migration to the adult thymus

    OpenAIRE

    Zlotoff, Daniel A.; Bhandoola, Avinash

    2011-01-01

    While most hematopoietic lineages develop in the bone marrow (BM), T cells uniquely complete their development in the specialized environment of the thymus. Hematopoietic stem cells with long-term self-renewal capacity are not present in the thymus. As a result, continuous T cell development requires that BM-derived progenitors be imported into the thymus throughout adult life. The process of thymic homing begins with the mobilization of progenitors out of the bone marrow, continues with thei...

  15. 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.

  16. Vascular Distribution of Glioblastoma Multiforme at Diagnosis

    Science.gov (United States)

    Yohay, K.; Wolf, D.S.; Aronson, L.J.; Duus, M.; Melhem, E.R.; Cohen, K.J.

    2013-01-01

    Summary Treatment of high-grade gliomas with selective intra-arterial (IA) administration of chemotherapies has been proposed, and utilized as a therapeutic modality. This approach offers the conceptual benefit of providing maximal delivery of the agent to the tumor bed, while potentially reducing systemic exposure to the agent. This retrospective study was designed to determine the vascular distribution of glioblastoma multiforme (GBM) at the time of diagnosis in an effort to determine what proportion of patients would likely be candidates for this approach. The preoperative MRI scans of 50 patients with GBM were analyzed and compared to published normative data of intracranial vascular distribution. Vascular distribution was determined by analyzing post-gadolinium axial and coronal T1 images, axial T2 images, and axial T2 images with an additional 1 cm margin (T2 + 1 cm) added in all dimensions. T1 analysis demonstrated 60% of tumors in a single vascular distribution. T2 analysis of these tumors reduced that number to 34%. When the T2 + 1 cm margin was utilized, only 6% of tumors were in a single vascular distribution. 66% of tumors were limited to the anterior circulation on T1 imaging but only 34% on T2 + 1 cm imaging. 30% of tumors were also within the distribution of the anterior choroidal artery. These findings suggest that the use of selective IA administration of agents is necessarily limited to a fraction of presenting patients or will require administration via multiple cerebral arteries. PMID:23472735

  17. 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.

  18. 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.

  19. 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.

  20. Serum-Free Generation of Multipotent Mesoderm (Kdr-positive) Progenitor Cells in Mouse Embryonic Stem Cells For Functional Genomics Screening

    Science.gov (United States)

    McKeithan, Wesley; Colas, Alexandre; Bushway, Paul J.; Ray, Saugata; Mercola, Mark

    2013-01-01

    This unit describes a robust protocol for producing multipotent Kdr-expressing mesoderm progenitor cells in serum-free conditions and functional genomics screening using these cells. Kdr-positive cells are known to be able to differentiate into a wide array of mesoderm derivatives including, vascular endothelial cells, cardiomyocytes, hematopietic progenitors and smooth muscle cells. The efficient generation of such progenitor cells is of particular interest because it permits subsequent steps in cardiovascular development to be analyzed in detail, including deciphering the mechanisms that direct differentiation. The oligonucleotide transfection protocol used to functionally screen siRNA and microRNA libraries is a powerful tool to reveal networks of genes, signaling proteins and microRNAs that control the diversification of cardiovascular lineages from multipotent progenitors. The discussion addresses technical limitations, troubleshooting and potential applications. PMID:23154934

  1. 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 ...

  2. csrnp1a is necessary for the development of primitive hematopoiesis progenitors in zebrafish.

    Directory of Open Access Journals (Sweden)

    Jaime Espina

    Full Text Available The CSRNP (cystein-serine-rich nuclear protein transcription factors are conserved from Drosophila to human. Functional studies in mice, through knockout for each of their paralogs, have resulted insufficient to elucidate the function of this family of proteins in vertebrate development. Previously, we described the function of the zebrafish ortholog, Csnrp1/Axud1, showing its essential role in the survival and proliferation of cephalic progenitors. To extend our understanding of this family, we have studied the function of its paralog csrnp1a. Our results show that csrnp1a is expressed from 0 hpf, until larval stages, particularly in cephalic territories and in the intermediate cell mass (ICM. Using morpholinos in wild type and transgenic lines we observed that Csrnp1a knockdown generates a mild reduction in head size and a depletion of blood cells in circulation. This was combined with in situ hybridizations to analyze the expression of different mesodermal and primitive hematopoiesis markers. Morphant embryos have impaired blood formation without disruption of mesoderm specification, angiogenesis or heart development. The reduction of circulating blood cells occurs at the hematopoietic progenitor level, affecting both the erythroid and myeloid lineages. In addition, cell proliferation was also altered in hematopoietic anterior sites, specifically in spi1 expression domain. These and previous observations suggest an important role of Csnrps transcription factors in progenitor biology, both in the neural and hematopoietic linages.

  3. 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.

  4. 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.

  5. 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.

  6. Aldosterone and vascular damage.

    Science.gov (United States)

    Duprez, D; De Buyzere, M; Rietzschel, E R; Clement, D L

    2000-06-01

    Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

  7. 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.

  8. Potential of cardiac stem/progenitor cells and induced pluripotent stem cells for cardiac repair in ischaemic heart disease

    OpenAIRE

    Wang, Wei Eric; Chen, Xiongwen; Houser, Steven R.; Zeng, Chunyu

    2013-01-01

    Stem cell therapy has emerged as a promising strategy for cardiac and vascular repair. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. CS/PCs (cardiac stem/progenitor cells) are one type of adult stem cell with the potential to differentiate into cardiac lineages (cardiomyocytes, smooth muscle cells and endothelial cells). iPSCs (induced pluripotent stem cells) also ha...

  9. Vascular Cognitive Impairment.

    Science.gov (United States)

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  10. 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

  11. Red blood cells in retinal vascular disorders.

    Science.gov (United States)

    Agrawal, Rupesh; Sherwood, Joseph; Chhablani, Jay; Ricchariya, Ashutosh; Kim, Sangho; Jones, Philip H; Balabani, Stavroula; Shima, David

    2016-01-01

    Microvascular circulation plays a vital role in regulating physiological functions, such as vascular resistance, and maintaining organ health. Pathologies such as hypertension, diabetes, or hematologic diseases affect the microcirculation posing a significant risk to human health. The retinal vasculature provides a unique window for non-invasive visualisation of the human circulation in vivo and retinal vascular image analysis has been established to predict the development of both clinical and subclinical cardiovascular, metabolic, renal and retinal disease in epidemiologic studies. Blood viscosity which was otherwise thought to play a negligible role in determining blood flow based on Poiseuille's law up to the 1970s has now been shown to play an equally if not a more important role in controlling microcirculation and quantifying blood flow. Understanding the hemodynamics/rheology of the microcirculation and its changes in diseased states remains a challenging task; this is due to the particulate nature of blood, the mechanical properties of the cells (such as deformability and aggregability) and the complex architecture of the microvasculature. In our review, we have tried to postulate a possible role of red blood cell (RBC) biomechanical properties and laid down future framework for research related to hemorrheological aspects of blood in patients with retinal vascular disorders.

  12. Mechanisms of oligodendrocyte regeneration from ventricular-subventricular zone-derived progenitor cells in white matter diseases

    Directory of Open Access Journals (Sweden)

    Takakuni eMaki

    2013-12-01

    Full Text Available White matter dysfunction is an important part of many CNS disorders including multiple sclerosis and vascular dementia. Within injured areas, myelin loss and oligodendrocyte death may trigger endogenous attempts at regeneration. However, during disease progression, remyelination failure may eventually occur due to impaired survival/proliferation, migration/recruitment, and differentiation of oligodendrocyte precursor cells (OPCs. The ventricular-subventricular zone (V-SVZ and the subgranular zone are the main sources of neural stem/progenitor cells (NSPCs, which can give rise to neurons as well as OPCs. Under normal conditions in the adult brain, the V-SVZ progenitors generate a large number of neurons with a small number of oligodendrocyte lineage cells. However, after demyelination, the fate of V-SVZ-derived progenitor cells shifts from neurons to OPCs, and these newly generated OPCs migrate to the demyelinating lesions to ease white matter damage. In this mini-review, we will summarize the recent studies on extrinsic (e.g., vasculature, extracellular matrix, cerebrospinal fluid and intrinsic (e.g., transcription factors, epigenetic modifiers factors, which mediate oligodendrocyte generation from the V-SVZ progenitor cells. A deeper understanding of the mechanisms that regulate the fate of V-SVZ progenitor cells may lead to new therapeutic approaches for ameliorating white matter dysfunction and damage in CNS disorders.

  13. Poikiloderma vasculare atrophicans

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    1994-01-01

    Full Text Available A 65 year old lady presented with generalised pruritus and discolouration of skin and mucous membranes of 5 years duration. The histopathology from the cutaneous lesions revealed features suggestive of poikiloderma vasculare atrophicans (PVA. Investigations did not reveal any underlying connective tissue disease,lymphoma or systemic disease. A diagnosis of idiopathic poikiloderma vasculare atrophicans was made.

  14. [Vascular factors in glaucoma].

    Science.gov (United States)

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation.

  15. Arterial vascularization patterns of the splenium: An anatomical study.

    Science.gov (United States)

    Kahilogullari, G; Comert, A; Ozdemir, M; Brohi, R A; Ozgural, O; Esmer, A F; Egemen, N; Karahan, S T

    2013-09-01

    The aim of this study was to provide detailed information about the arterial vascularization of the splenium of the corpus callosum (CC). The splenium is unique in that it is part of the largest commissural tract in the brain and a region in which pathologies are seen frequently. An exact description of the arterial vascularization of this part of the CC remains under debate. Thirty adult human brains (60 hemispheres) were obtained from routine autopsies. Cerebral arteries were separately cannulated and injected with colored latex. Then, the brains were fixed in formaldehyde, and dissections were performed using a surgical microscope. The diameter of the arterial branches supplying the splenium of the CC at their origin was investigated, and the vascularization patterns of these branches were observed. Vascular supply to the splenium was provided by the anterior pericallosal artery (40%) from the anterior circulation and by the posterior pericallosal artery (88%) and posterior accessory pericallosal artery (50%) from the posterior circulation. The vascularization pattern of the splenium differs in each hemisphere and is usually supplied by multiple branches. The arterial vascularization of the splenium of the CC was studied comprehensively considering the ongoing debate and the inadequacy of the studies on this issue currently available in the literature. This anatomical knowledge is essential during the treatment of pathologies in this region and especially for splenial arteriovenous malformations.

  16. 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

  17. 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.

  18. Carbon monoxide and bile pigments: surprising mediators of vascular function.

    Science.gov (United States)

    Durante, William

    2002-08-01

    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

  19. 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

  20. 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

  1. [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.

  2. 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.

  3. Core-Collapse supernovae and its progenitors

    CERN Document Server

    Bose, Subhash; Misra, Kuntal

    2016-01-01

    Massive stars unable to sustain gravitational collapse, at the end of nuclear burning stage, turns out into core-collapse supernovae, leaving behind compact objects like neutron stars or black holes. The progenitor properties like mass and metallicity primarily governs the explosion parameters and type of compact remnant. In this contribution we summarize observational study of three Core Collapse type IIP SNe 2012aw, 2013ab and 2013ej, which are rigorously observed from ARIES and other Indian observatories and discuss their progenitor and explosion properties.

  4. 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...

  5. 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.

  6. 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.

  7. Learning Circulant Sensing Kernels

    Science.gov (United States)

    2014-03-01

    learned dictionaries. Examples of analytic dictionaries include the discrete cosine basis, various wavelets bases , as well as tight frames. Some of them...Compressive sensing based high resolution channel estimation for OFDM system. To appear in IEEE Journal of Selected Topics in Signal Processing, Special...theoretical and computational properties to a (partial) circulant matrix of the same size, our discussions below are based exclusively on the circulant

  8. 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

  9. 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.

  10. Characterization of hepatic progenitors from human fetal liver using CD34 as a hepatic progenitor marker

    Institute of Scientific and Technical Information of China (English)

    Parveen Nyamath; Ayesha AM; Aejaz Habeeb; Sanjeev Khosla; Aleem A Khan; CM Habibullah

    2007-01-01

    AIM: To enrich putative hepatic progenitors from the developing human fetal liver using CD34 as a marker.METHODS: Aborted fetuses of 13-20 wk were used for the isolation of liver cells. The cells were labeled with anti CD34; a marker used for isolating progenitor population and the cells were sorted using magnetic cell sorting. The positive fractions of cells were assessed for specific hepatic markers. Further, these cells were cultured in vitro for long term investigation.RESULTS: Flow cytometric and immunocytochemical analysis for alphafetoprotein (AFP) showed that the majority of the enriched CD34 positive cells were positive for AFP. Furthermore, these enriched cells proliferated in the long term and maintained hepatic characteristics in in vitro culture.CONCLUSION: The study shows that aborted human fetal liver is a potential source for isolation of hepatic progenitors for clinical applications. The study also demonstrates that CD34 can be a good marker for the enrichment of progenitor populations.

  11. Targeting human oligodendrocyte progenitors for myelin repair.

    Science.gov (United States)

    Dietz, Karen C; Polanco, Jessie J; Pol, Suyog U; Sim, Fraser J

    2016-09-01

    Oligodendrocyte development has been studied for several decades, and has served as a model system for both neurodevelopmental and stem/progenitor cell biology. Until recently, the vast majority of studies have been conducted in lower species, especially those focused on rodent development and remyelination. In humans, the process of myelination requires the generation of vastly more myelinating glia, occurring over a period of years rather than weeks. Furthermore, as evidenced by the presence of chronic demyelination in a variety of human neurologic diseases, it appears likely that the mechanisms that regulate development and become dysfunctional in disease may be, in key ways, divergent across species. Improvements in isolation techniques, applied to primary human neural and oligodendrocyte progenitors from both fetal and adult brain, as well as advancements in the derivation of defined progenitors from human pluripotent stem cells, have begun to reveal the extent of both species-conserved signaling pathways and potential key differences at cellular and molecular levels. In this article, we will review the commonalities and differences in myelin development between rodents and man, describing the approaches used to study human oligodendrocyte differentiation and myelination, as well as heterogeneity within targetable progenitor pools, and discuss the advances made in determining which conserved pathways may be both modeled in rodents and translate into viable therapeutic strategies to promote myelin repair.

  12. Single Degenerate Progenitors of Type Ia Supernovae

    Science.gov (United States)

    Bours, Madelon; Toonen, Silvia; Nelemans, Gijs

    2013-01-01

    There is a general agreement that Type Ia supernovae correspond to the thermonuclear runaway of a white dwarf (WD) in a compact binary. The details of these progenitor systems are still unclear. Using the population synthesis code SeBa and several assumption for the WD retention efficiency, we estimate the delay times and supernova rates for the single degenerate scenario.

  13. Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

    Directory of Open Access Journals (Sweden)

    Julian Pulecio

    2016-10-01

    Full Text Available Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41+, display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.

  14. Intracranial Vascular Treatments

    Science.gov (United States)

    ... full size with caption Related Articles and Media Gamma Knife Linear Accelerator Catheter Embolization Angioplasty and Vascular Stenting Proton Therapy Radiation Dose in X-Ray and CT Exams Stereotactic ...

  15. Congenital Vascular Malformation

    Science.gov (United States)

    ... also be effective for small, localized birthmarks (port wine stains). Patients with a rare venous malformation (Kleppel– ... 3) non-profit organization focused on providing public education and improving awareness about vascular diseases. For more ...

  16. Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.

    Science.gov (United States)

    Relucio, Jenne; Menezes, Michael J; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Colognato, Holly

    2012-10-01

    The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2-/- mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2-/- VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2-/- corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that prosurvival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately.

  17. 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.

  18. 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

  19. 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

  20. [Complex vascular access].

    Science.gov (United States)

    Mangiarotti, G; Cesano, G; Thea, A; Hamido, D; Pacitti, A; Segoloni, G P

    1998-03-01

    Availability of a proper vascular access is a basic condition for a proper extracorporeal replacement in end-stage chronic renal failure. However, biological factors, management and other problems, may variously condition their middle-long term survival. Therefore, personal experience of over 25 years has been critically reviewed in order to obtain useful information. In particular "hard" situations necessitating complex procedures have been examined but, if possible, preserving the peripherical vascular features.

  1. Ageing and vascular ageing

    OpenAIRE

    2006-01-01

    There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, di...

  2. Vascular compression syndromes.

    Science.gov (United States)

    Czihal, Michael; Banafsche, Ramin; Hoffmann, Ulrich; Koeppel, Thomas

    2015-11-01

    Dealing with vascular compression syndromes is one of the most challenging tasks in Vascular Medicine practice. This heterogeneous group of disorders is characterised by external compression of primarily healthy arteries and/or veins as well as accompanying nerval structures, carrying the risk of subsequent structural vessel wall and nerve damage. Vascular compression syndromes may severely impair health-related quality of life in affected individuals who are typically young and otherwise healthy. The diagnostic approach has not been standardised for any of the vascular compression syndromes. Moreover, some degree of positional external compression of blood vessels such as the subclavian and popliteal vessels or the celiac trunk can be found in a significant proportion of healthy individuals. This implies important difficulties in differentiating physiological from pathological findings of clinical examination and diagnostic imaging with provocative manoeuvres. The level of evidence on which treatment decisions regarding surgical decompression with or without revascularisation can be relied on is generally poor, mostly coming from retrospective single centre studies. Proper patient selection is critical in order to avoid overtreatment in patients without a clear association between vascular compression and clinical symptoms. With a focus on the thoracic outlet-syndrome, the median arcuate ligament syndrome and the popliteal entrapment syndrome, the present article gives a selective literature review on compression syndromes from an interdisciplinary vascular point of view.

  3. Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation

    Institute of Scientific and Technical Information of China (English)

    Ai-wu SHI; Xiao-bin WANG; Feng-xiang LU; Min-min ZHU; Xiang-qing KONG; Ke-jiang CAO

    2009-01-01

    Aim: To investigate the effect of ginsenoside Rgl on the migration, adhesion, proliferation, and VEGF expression of endothe-lial progenitor cells (EPCs).Methods: EPCs were isolated from human peripheral blood and incubated with different concentrations of ginsenoside Rgl (0.1, 0.5, 1.0, and 5.0 μmol/L) and vehicle controls. EPC migration was detected with a modified Boyden chamber assay. EPC adhesion was determined by counting adherent cells on fibronectin-coated culture dishes. EPC proliferation was analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro vasculogenesis was assayed using an in vitro vasculogenesis detection kit. A VEGF-ELISA kit was used to measure the amount of VEGF protein in the cell culture medium.Results: Ginsenoside Rgl promoted EPC adhesionp proliferation, migration and in vitro vasculogenesis in a dose- and time-dependent manner. Cell cycle analysis showed that 5.0 μmol/L of ginsenoside Rgl significantly increased the EPC prolifera-tive phase (S phase) and decreased the resting phase (G0/G1 phase). Ginsenoside Rgl increased vascular endothelial growth factor production.Conclusion: The results indicate that ginsenoside Rgl promotes proliferation, migration, adhesion and in vitro vasculogen-esis.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Successful one-lung ventilation in a patient with the Fontan circulation undergoing thoracoscopic procedure.

    Science.gov (United States)

    Cvetkovic, Draginja; Ramzy, Wassim; Vitale, Salvatore; Malekan, Ramin; Warsy, Irfan

    2014-12-01

    Over the course of the past 4 decades, the survival of patients with the Fontan circulation has improved and today they often present for noncardiac surgery anesthesia care. In patients with the Fontan circulation, pulmonary blood flow is passive and anesthetic management is directed at reducing pulmonary vascular resistance and maintaining adequate cardiac output. One-lung ventilation can have unfavorable effects on the Fontan circulation due to hypoxia, hypercarbia, and increased airway pressure. We present a case of successful one-lung ventilation in a patient with the Fontan circulation and describe the perioperative anesthetic management.

  9. Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults

    Science.gov (United States)

    Matrix Gla protein (MGP) is a calcification inhibitor in vascular tissue. To function, MGP must be carboxylated by vitamin K. Evidence suggests that circulating uncarboxylated MGP (ucMGP) is elevated in diseased individuals with vascular calcification. The extent to which this reflects vitamin K’s r...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Kernels in circulant digraphs

    Directory of Open Access Journals (Sweden)

    R. Lakshmi

    2014-06-01

    Full Text Available A kernel $J$ of a digraph $D$ is an independent set of vertices of $D$ such that for every vertex $w,in,V(D,setminus,J$ there exists an arc from $w$ to a vertex in $J.$ In this paper, among other results, a characterization of $2$-regular circulant digraph having a kernel is obtained. This characterization is a partial solution to the following problem: Characterize circulant digraphs which have kernels; it appeared in the book {it Digraphs - theory, algorithms and applications}, Second Edition, Springer-Verlag, 2009, by J. Bang-Jensen and G. Gutin.

  15. Sumatriptan does not change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Petersen, Jesper; Wienecke, Troels;

    2009-01-01

    not differ between the four vascular compartments (P=0.49). It was found that Sumatriptan did not change the levels of circulating CGRP in the intra or extracerebral circulation in healthy volunteers. This speaks against a direct CGRP-reducing effect of sumatriptan in vivo in humans when the trigemino...

  16. Derivation of myoepithelial progenitor cells from bipotent mammary stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Xiangshan Zhao

    Full Text Available There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Recent molecular profiling has identified six major subtypes of breast cancer: basal-like, ErbB2-overexpressing, normal breast epithelial-like, luminal A and B, and claudin-low subtypes. To help understand the relationship among mammary stem/progenitor cells and breast cancer subtypes, we have recently derived distinct hTERT-immortalized human mammary stem/progenitor cell lines: a K5(+/K19(- type, and a K5(+/K19(+ type. Under specific culture conditions, bipotent K5(+/K19(- stem/progenitor cells differentiated into stable clonal populations that were K5(-/K19(- and exhibit self-renewal and unipotent myoepithelial differentiation potential in contrast to the parental K5(+/K19(- cells which are bipotent. These K5(-/K19(- cells function as myoepithelial progenitor cells and constitutively express markers of an epithelial to mesenchymal transition (EMT and show high invasive and migratory abilities. In addition, these cells express a microarray signature of claudin-low breast cancers. The EMT characteristics of an un-transformed unipotent mammary myoepithelial progenitor cells together with claudin-low signature suggests that the claudin-low breast cancer subtype may arise from myoepithelial lineage committed progenitors. Availability of immortal MPCs should allow a more definitive analysis of their potential to give rise to claudin-low breast cancer subtype and facilitate biological and molecular/biochemical studies of this disease.

  17. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

    Directory of Open Access Journals (Sweden)

    Yaling Liu

    Full Text Available We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.

  18. Osterix-Cre Labeled Progenitor Cells Contribute to the Formation and Maintenance of the Bone Marrow Stroma

    Science.gov (United States)

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S.; Wang, Wen; Rowe, David W.; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma. PMID:23951132

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. On the progenitor of V838 Monocerotis

    CERN Document Server

    Tylenda, R; Szczerba, R

    2004-01-01

    We summarize and analyze the available observational data on the progenitor and the enviroment of V838 Mon, the object that erupted in January 2002. We show that the radio and infrared observed matter in the vicinity of V838 Mon could not have its origin in mass loss from V838 Mon but is of interstellar origin. Also from the light echo evolution we conclude that the reflecting dust is of the same nature and not blown by V838 Mon in the past. This is compatible with the photometric data for the progenitor of V838 Mon, from which we exclude the possibility that the object before eruption was an evolved red giant star (AGB or RGB star). We find that most likely it was a main sequence star of \\~5-10 M_sun.

  4. Ageing and vascular ageing

    Science.gov (United States)

    Jani, B; Rajkumar, C

    2006-01-01

    There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, diabetes, and end stage renal failure. Changes in arterial compliance can be present before the clinical manifestation of cardiovascular disease. Pharmacological and non‐pharmacological measures have been shown to improve arterial compliance. Arterial compliance may constitute an early cardiovascular risk marker and may be useful in assessing the effects of drugs on the cardiovascular system. Pharmacogenetics and genetics of arterial compliance in the future will improve our knowledge and understanding about vascular ageing. PMID:16754702

  5. Thymosin β4 Improves Differentiation and Vascularization of EHTs

    Science.gov (United States)

    Ziegler, Tilman; Hinkel, Rabea; Stöhr, Andrea; Eschenhagen, Thomas; Laugwitz, Karl-Ludwig; le Noble, Ferdinand; David, Robert; Hansen, Arne

    2017-01-01

    Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation. We examined the potential impact of Tβ4 to enhance maturation of cardiomyocytes from iPSCs. Assessing the expression of transcription factors associated with cardiac differentiation, we were able to demonstrate the increased generation of cells displaying cardiomyocyte characteristics in vitro. Furthermore, we demonstrated, in a zebrafish model of embryonic vascular development, that Tβ4 is crucial for the proper execution of lymphatic and angiogenic vessel sprouting. Finally, utilizing Tβ4-transduced EHTs generated from mice genetically engineered to label endothelial cells in vitro, we show that treatment with Tβ4 promotes vascularization and contractility in EHTs, highlighting Tβ4 as a growth factor improving the formation of cardiomyocytes from iPSC and enhancing the performance of EHTs generated from neonatal cardiomyocytes. PMID:28191018

  6. Late Posthemorrhagic Structural and Functional Changes in Pulmonary Circulation Arteries

    Directory of Open Access Journals (Sweden)

    S. A. Andreyeva

    2008-01-01

    Full Text Available Objective: to reveal the major regularities and mechanisms of morphological changes in the rat pulmonary circulation arteries in the late posthemorrhagic period and to compare them with age-related features of the vessels. Materials and methods: experiments to generate graduated hemorrhagic hypotension with the blood pressure being maintained at 40 mm Hg were carried out on young (5—6-month albino male Wistar rats. Throughout hypotension and 60 days after blood loss, the blood was tested to determine low and average molecular-weight substances by spectrophotometry and the pro- and antioxidative systems by chemiluminescence. Pulmonary circulation arteries were morphologically studied in young animals, rats in the late posthemorrhagic period and old (24—25-month rats. Results. Sixty-minute hemorrhagic hypotension leads to the development of endotoxemia and imbalance of the pro- and antioxidative systems, the signs of which are observed in the late periods (2 months after hypotension. At the same time, the posthemorrhagic period is marked by the significant pulmonary circulation arterial morphological changes comparable with their age-related alterations in old rat. This shows up mainly in the reorganization of a connective tissue component in the vascular wall: the elevated levels of individual collagen fibers, their structural changes, elastic medial membrane destruction and deformity. At the same time, there is a change in the morphometric parameters of vessels at all study stages while their lowered flow capacity is only characteristic for intraorgan arteries. Conclusion: The increased activity of free radical oxidation and endotoxemia may be believed to be one of the causes of morphological changes in pulmonary circulation arteries in the late posthemorrhagic period, which is similar to age-related vascular alterations. Key words: hemorrhagic hypotension, pulmonary circulation arteries, free radical oxidation, endotoxemia, remodeling, late

  7. Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model

    Science.gov (United States)

    Lavasani, Mitra; Robinson, Andria R.; Lu, Aiping; Song, Minjung; Feduska, Joseph M.; Ahani, Bahar; Tilstra, Jeremy S.; Feldman, Chelsea H.; Robbins, Paul D.; Niedernhofer, Laura J.; Huard, Johnny

    2012-01-01

    With ageing, there is a loss of adult stem cell function. However, there is no direct evidence that this has a causal role in ageing-related decline. We tested this using muscle-derived stem/progenitor cells (MDSPCs) in a murine progeria model. Here we show that MDSPCs from old and progeroid mice are defective in proliferation and multilineage differentiation. Intraperitoneal administration of MDSPCs, isolated from young wild-type mice, to progeroid mice confer significant lifespan and healthspan extension. The transplanted MDSPCs improve degenerative changes and vascularization in tissues where donor cells are not detected, suggesting that their therapeutic effect may be mediated by secreted factor(s). Indeed, young wild-type-MDSPCs rescue proliferation and differentiation defects of aged MDSPCs when co-cultured. These results establish that adult stem/progenitor cell dysfunction contributes to ageing-related degeneration and suggests a therapeutic potential of post-natal stem cells to extend health. PMID:22215083

  8. 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

  9. 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

  10. Involvement of microparticles in diabetic vascular complications.

    Science.gov (United States)

    Tsimerman, Gala; Roguin, Ariel; Bachar, Anat; Melamed, Eyal; Brenner, Benjamin; Aharon, Anat

    2011-08-01

    Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear. We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels of MPs originated from platelet and endothelial cells and negatively-charged phospholipid-bearing MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (1.8, p≥0.002). MPs of all T2DM patients induced a more than two-fold increase in endothelial cell TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were longest and most stable in endothelial cells that were incubated with MPs of healthy controls, whereas no tube formation occurred in MPs of diabetic patients with coronary artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced branched tube networks that were unstable and collapsed over time. This study demonstrates that MP characteristics are related to the specific type of vascular complications and may serve as a bio-marker for the pro- coagulant state and vascular pathology in patients with T2DM.

  11. Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-13-1-0244 TITLE: Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells PRINCIPAL...2014 - 31 Aug 2015 4. TITLE AND SUBTITLE Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells 5a. CONTRACT NUMBER 5b...the development of knee osteoarthritis (OA). New treatments centered on the stem/ progenitor cell population resident within the adult meniscus will be

  12. 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...

  13. Enhanced antitumor efficacy of a vascular disrupting agent combined with an antiangiogenic in a rat liver tumor model evaluated by multiparametric MRI.

    Directory of Open Access Journals (Sweden)

    Feng Chen

    Full Text Available A key problem in solid tumor therapy is tumor regrowth from a residual viable rim after treatment with a vascular disrupting agent (VDA. As a potential solution, we studied a combined treatment of a VDA and antiangiogenic. This study was approved by the institutional ethical committee for the use and care of laboratory animals. Rats with implanted liver tumors were randomized into four treatment groups: 1 Zd6126 (Zd; 2 Thalidomide (Tha; 3 Zd in combination with Tha (ZdTha; and 4 controls. Multiparametric MRIs were performed and quantified before and after treatment. Circulating endothelial progenitor cells (EPCs and plasma stromal cell-derived factor-1α (SDF-1α were monitored. Tumor apoptosis, necrosis, and microvessels were verified by histopathology. A single use of Zd or Tha did not significantly delay tumor growth. The combined ZdTha showed enhanced antitumor efficacy due to synergistic effects; it induced a cumulative tumor apoptosis or necrosis, which resulted in significant delay in tumor growth and reduction in the viable tumor rim; it also reduced tumor vessel permeability; and it improved tumor hemodynamic indexes, most likely via a transient normalization of tumor vasculature induced by Tha. A stepwise linear regression analysis showed that the apparent diffusion coefficient was an independent predictor of tumor growth. We found no significant increases in Zd-induced circulating EPCs or plasma SDF-1α. ZdTha showed improved therapeutic efficacy in solid tumors compared to either agent alone. The therapeutic effects were successfully tracked in vivo with multiparametric MRI.

  14. The fetal circulation.

    Science.gov (United States)

    Kiserud, Torvid; Acharya, Ganesh

    2004-12-30

    Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.

  15. [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.

  16. Human endothelial stem/progenitor cells, angiogenic factors and vascular repair

    OpenAIRE

    Watt, Suzanne M.; Athanassopoulos, Athanasios; Harris, Adrian L.; Tsaknakis, Grigorios

    2010-01-01

    Neovascularization or new blood vessel formation is of utmost importance not only for tissue and organ development and for tissue repair and regeneration, but also for pathological processes, such as tumour development. Despite this, the endothelial lineage, its origin, and the regulation of endothelial development and function either intrinsically from stem cells or extrinsically by proangiogenic supporting cells and other elements within local and specific microenvironmental niches are stil...

  17. Apoptosis of endothelial progenitor cells in a metabolic syndrome experimental model

    Science.gov (United States)

    Lembo, Carina; Lopez-Aguilera, Francisco; Diez, Emiliano R.; Renna, Nicolás; Vazquez-Prieto, Marcela; Miatello, Roberto M.

    2012-01-01

    Aim: This study tests the hypothesis postulating that metabolic syndrome induced by chronic administration of fructose to spontaneously hypertensive rats (FFHR) generates impairment in vascular repair by endothelial progenitor cells (EPC). Materials and Methods: To characterize the vascular adverse environment present in this experimental model we measured: NAD(P)H oxidase activity, eNOS activity, presence of apoptosis in the arterial wall, all these parameters were most affected in the FFHR group. Also, we found decreased level and proliferative capacity of EPC measured by flow cytometry and colonies forming units assay in cultured cells, respectively, in both groups treated with fructose; FFHR (SHR fructose fed rats) and FFR (WKY fructose fed rats) compared with their controls; SHR and WKY. Results: The fructose-fed groups FFR and SHR also showed an incremented number of apoptotic (annexinV+/7AADdim) EPC measured by flow cytometry that returns to almost normal values after eliminating fructose administration. Conclusion: Our findings suggest that increased apoptosis levels of EPC generated in this experimental model could bein part the underlying cause for the impaired vascular repair by in EPC. PMID:23233774

  18. 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 durin...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress.......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...

  19. Pharmacologically active microcarriers for endothelial progenitor cell support and survival.

    Science.gov (United States)

    Musilli, Claudia; Karam, Jean-Pierre; Paccosi, Sara; Muscari, Claudio; Mugelli, Alessandro; Montero-Menei, Claudia N; Parenti, Astrid

    2012-08-01

    The regenerative potential of endothelial progenitor cell (EPC)-based therapies is limited due to poor cell viability and minimal retention following application. Neovascularization can be improved by means of scaffolds supporting EPCs. The aim of the present study was to investigate whether human early EPCs (eEPCs) could be efficiently cultured on pharmacologically active microcarriers (PAMs), made with poly(d,l-lactic-coglycolic acid) and coated with adhesion/extracellular matrix molecules. They may serve as a support for stem cells and may be used as cell carriers providing a controlled delivery of active protein such as the angiogenic factor, vascular endothelial growth factor-A (VEGF-A). eEPC adhesion to fibronectin-coated PAMs (FN-PAMs) was assessed by means of microscopic evaluation and by means of Alamar blue assay. Phospho ERK(1/2) and PARP-1 expression was measured by means of Western blot to assess the survival effects of FN-PAMs releasing VEGF-A (FN-VEGF-PAMs). The Alamar blue assay or a modified Boyden chamber assay was employed to assess proliferative or migratory capacity, respectively. Our data indicate that eEPCs were able to adhere to empty FN-PAMs within a few hours. FN-VEGF-PAMs increased the ability of eEPCs to adhere to them and strongly supported endothelial-like phenotype and cell survival. Moreover, the release of VEGF-A by FN-PAMs stimulated in vitro HUVEC migration and proliferation. These data strongly support the use of PAMs for supporting eEPC growth and survival and for stimulating resident mature human endothelial cells.

  20. Neurobiology of Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Ana-Maria Enciu

    2011-01-01

    Full Text Available Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach.

  1. 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.

  2. [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.

  3. Adhesion in vascular biology

    OpenAIRE

    2014-01-01

    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is call...

  4. 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

  5. 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.

  6. 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.

  7. The progenitors of supernovae Type Ia

    Science.gov (United States)

    Toonen, Silvia

    2014-09-01

    Despite the significance of Type Ia supernovae (SNeIa) in many fields in astrophysics, SNeIa lack a theoretical explanation. SNeIa are generally thought to be thermonuclear explosions of carbon/oxygen (CO) white dwarfs (WDs). The canonical scenarios involve white dwarfs reaching the Chandrasekhar mass, either by accretion from a non-degenerate companion (single-degenerate channel, SD) or by a merger of two CO WDs (double-degenerate channel, DD). The study of SNeIa progenitors is a very active field of research for binary population synthesis (BPS) studies. The strength of the BPS approach is to study the effect of uncertainties in binary evolution on the macroscopic properties of a binary population, in order to constrain binary evolutionary processes. I will discuss the expected SNeIa rate from the BPS approach and the uncertainties in their progenitor evolution, and compare with current observations. I will also discuss the results of the POPCORN project in which four BPS codes were compared to better understand the differences in the predicted SNeIa rate of the SD channel. The goal of this project is to investigate whether differences in the simulated populations are due to numerical effects or whether they can be explained by differences in the input physics. I will show which assumptions in BPS codes affect the results most and hence should be studied in more detail.

  8. Single degenerate supernova type Ia progenitors

    CERN Document Server

    Bours, M C P; Nelemans, G

    2013-01-01

    There is general agreement that supernovae Ia correspond to the thermonuclear runaway of a white dwarf that is part of a compact binary, but the details of the progenitor systems are still unknown and much debated. One of the proposed progenitor theories is the single-degenerate channel in which a white dwarf accretes from a companion, grows in mass, reaches a critical mass limit, and is then consumed after thermonuclear runaway sets in. However, there are major disagreements about the theoretical delay time distribution and the corresponding time-integrated supernova Ia rate from this channel. We investigate whether the differences are due to the uncertainty in the common envelope phase and the fraction of transferred mass that is retained by the white dwarf. This so-called retention efficiency may have a strong influence on the final amount and timing of supernovae Ia. Using the population synthesis code SeBa, we simulated large numbers of binaries for various assumptions on common envelopes and retention e...

  9. Magnetized massive stars as magnetar progenitors

    CERN Document Server

    Hu, Ren-Yu

    2009-01-01

    The origin of ultra-intense magnetic fields on magnetars is a mystery in modern astrophysics. We model the core collapse dynamics of massive progenitor stars with high surface magnetic fields in the theoretical framework of a self-similar general polytropic magnetofluid under the self-gravity with a quasi-spherical symmetry. With the specification of physical parameters such as mass density, temperature, magnetic field and wind mass loss rate on the progenitor stellar surface and the consideration of a rebound shock breaking through the stellar interior and envelope, we find a remnant compact object (i.e. neutron star) left behind at the centre with a radius of $\\sim 10^6$ cm and a mass range of $\\sim 1-3$ solar masses. Moreover, we find that surface magnetic fields of such kind of compact objects can be $\\sim 10^{14}-10^{15}$ G, consistent with those inferred for magnetars which include soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs). The magnetic field enhancement factor critically depend...

  10. 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...

  11. The Physicochemical Hydrodynamics of Vascular Plants

    Science.gov (United States)

    Stroock, Abraham D.; Pagay, Vinay V.; Zwieniecki, Maciej A.; Michele Holbrook, N.

    2014-01-01

    Plants live dangerously, but gracefully. To remain hydrated, they exploit liquid water in the thermodynamically metastable state of negative pressure, similar to a rope under tension. This tension allows them to pull water out of the soil and up to their leaves. When this liquid rope breaks, owing to cavitation, they catch the ends to keep it from unraveling and then bind it back together. In parallel, they operate a second vascular system for the circulation of metabolites though their tissues, this time with positive pressures and flow that passes from leaf to root. In this article, we review the current state of understanding of water management in plants with an emphasis on the rich coupling of transport phenomena, thermodynamics, and active biological processes. We discuss efforts to replicate plant function in synthetic systems and point to opportunities for physical scientists and engineers to benefit from and contribute to the study of plants.

  12. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Lavik, Erin B;

    2005-01-01

    To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs.......To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs....

  13. 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.

  14. HMG-CoA reductase inhibitors (statins), inflammation, and endothelial progenitor cells-New mechanistic insights of atherosclerosis.

    Science.gov (United States)

    Blum, Arnon

    2014-01-01

    Statins have been shown to favorably affect the prognosis of patients with risk factors to atherosclerosis-both as a primary and a secondary prevention. The beneficial effects observed with statin therapy are not merely related to changes in lipid profile but also are due to a positive effect on vascular inflammation and on immune-modulation of T lymphocytes and endothelial progenitor stem cells (EPCs). This dual effect has been demonstrated mainly in clinical trials where a change in endothelial function was observed within hours, much earlier than the effects of statins on the lipid profile (weeks). Based on all the knowledge that we have today questions were raised as to the mechanistic pathways that may explain the process of atherosclerosis and through this pathway to find better solutions and therapies to prevent and fight atherosclerosis. Our review will focus on the new updates in the field of inflammation and stem cells in vascular biology-in relation with atherosclerosis.

  15. 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)).

  16. 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.

  17. Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage

    DEFF Research Database (Denmark)

    Porse, Bo T; Bryder, David; Theilgaard-Mönch, Kim;

    2005-01-01

    CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription factor that couples lineage commitment to terminal differentiation and cell cycle arrest, and is found mutated in 9% of patients who have acute myeloid leukemia (AML). We previously showed that mutations which......, accumulation of myeloblasts and promyelocytes, and expansion of myeloid progenitor populations--all characteristics of AML. Circulating myeloblasts and hepatic leukocyte infiltration were observed, but thrombocytopenia, anemia, and elevated leukocyte count--normally associated with AML-were absent...

  18. GSK-3 is a master regulator of neural progenitor homeostasis

    Science.gov (United States)

    Kim, Woo-Yang; Wang, Xinshuo; Wu, Yaohong; Doble, Bradley W; Patel, Satish; Woodgett, James R; Snider, William D

    2016-01-01

    The development of the brain requires the exquisite coordination of progenitor proliferation and differentiation to achieve complex circuit assembly. It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because of its essential role in the RTK, Wnt and Shh signaling pathways. We created conditional mutations that deleted both the α and β forms of GSK-3 in mouse neural progenitors. GSK-3 deletion resulted in massive hyperproliferation of neural progenitors along the entire neuraxis. Generation of both intermediate neural progenitors and postmitotic neurons was markedly suppressed. These effects were associated with the dysregulation of β-catenin, Sonic Hedgehog, Notch and fibroblast growth factor signaling. Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development. PMID:19801986

  19. 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.

  20. Mast cell progenitors: origin, development and migration to tissues.

    Science.gov (United States)

    Dahlin, Joakim S; Hallgren, Jenny

    2015-01-01

    Mast cells in tissues are developed from mast cell progenitors emerging from the bone marrow in a process highly regulated by transcription factors. Through the advancement of the multicolor flow cytometry technique, the mast cell progenitor population in the mouse has been characterized in terms of surface markers. However, only cell populations with enriched mast cell capability have been described in human. In naïve mice, the peripheral tissues have a constitutive pool of mast cell progenitors. Upon infections in the gut and in allergic inflammation in the lung, the local mast cell progenitor numbers increase tremendously. This review focuses on the origin and development of mast cell progenitors. Furthermore, the evidences for cells and molecules that govern the migration of these cells in mice in vivo are described.

  1. Hepatic progenitor cells in human liver tumor development

    Institute of Scientific and Technical Information of China (English)

    Louis Libbrecht

    2006-01-01

    In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types.The available data indeed strongly suggest that most combined hepatocellular-cholangiocarcinomas arise from hepatic progenitor cells that retained their potential to differentiate into the hepatocytic and biliary lineages.Hepatic progenitor cells could also be the basis for some hepatocellular carcinomas and hepatocellular adenomas, although it is very difficult to determine the origin of an individual hepatocellular carcinoma. There is currently not enough data to make statements regarding a hepatic progenitor cell origin of cholangiocarcinoma.The presence of hepatic progenitor cell markers and the presence and extent of the cholangiocellular component are factors that are related to the prognosis of hepatocellular carcinomas and combined hepatocellularcholangiocarcinomas, respectively.

  2. 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.

  3. Clinical implications of disturbances of uterine vascular morphology and function.

    Science.gov (United States)

    Hickey, M; Fraser, I S

    2000-12-01

    Menstrual disturbances are one of the most common problems presenting to the gynaecologist. In order for the endometrium to bleed, vessels must break down. Disruption in the regulation of endometrial vascular growth and function has been found in association with spontaneous and sex steroid-induced disturbances of menstrual bleeding. Although circulating oestrogens and progestogens influence the endometrial vessels, this effect appears to be indirect, and regulation is primarily via local factors. Deficient vasoconstriction and haemostasis with excessive fibrinolysis is seen in menorrhagia. Breakthrough bleeding in users of progestogen-only contraceptives is associated with increased superficial vascular fragility and disruptions in the supporting basement membrane. Blood vessels in uterine fibroids are abnormal in distribution and appearance. Adenomyosis is also commonly associated with menstrual disturbance, and alterations in vascular distribution suggest altered angiogenesis. Successful human embryo implantation requires endometrial vascular breakdown. Excessive thrombosis associated with the antiphospholipid syndrome may interfere with this re-modelling and compromise implantation. Arteriovenous malformations are a rare but important cause of excessive or irregular vaginal bleeding. Abundant vessels with abnormal morphology, associated with aberrant angiogenesis can be seen, and embolization of these vessels may be an effective conservative treatment. Improved understanding of the regulation of the uterine vasculature is likely to lead to targeted therapies to prevent unscheduled vascular breakdown and to control menstrual disturbance at an endometrial level.

  4. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  5. 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.

  6. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens;

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...

  7. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Holst, J J; Møller, Søren;

    2000-01-01

    during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng...

  8. Mobilization of stem/progenitor cells by sulfated polysaccharides does not require selectin presence.

    Science.gov (United States)

    Sweeney, E A; Priestley, G V; Nakamoto, B; Collins, R G; Beaudet, A L; Papayannopoulou, T

    2000-06-06

    Employing carbohydrate ligands, which have been extensively used to block selectin function in vitro and in vivo, we have examined the involvement of such ligands in stem/progenitor cell mobilization in mice and monkeys. We found that sulfated fucans, branched and linear, are capable of increasing mature white cells in the periphery and mobilizing stem/progenitor cells of all classes (up to 32-fold) within a few hours posttreatment in a dose-dependent manner. To elicit the effect, the presence of sulfate groups was necessary, yet not sufficient, as certain sulfated hexosamines tested (chondroitin sulfates A or B) were ineffective. Significant mobilization of stem/progenitor cells and leukocytosis was elicited in selectin-deficient mice (L(-/-), PE(-/-), or LPE(-/-)) similar to that of wild-type controls, suggesting that the mode of action of sulfated fucans is not through blockade of known selectins. Other mechanisms have been entertained, in particular, the release of chemokines/cytokines, including some previously implicated in mobilization. Significant increases were documented in the levels of seven circulating chemokines/cytokines within a few hours after fucan sulfate treatment and support such a proposition. Additionally, an increase was noted in plasma metalloproteinase (MMP) 9, which might independently contribute to the mobilization process by enzymatically facilitating chemokine/cytokine release. Mobilization by sulfated polysaccharides provides a distinct paradigm in the mobilization process and uncovers an additional novel in vivo biological role for sulfated glycans. As similarly sulfated compounds were ineffective in vivo, the data also underscore the fact that polysaccharides with similar structures may elicit diverse in vivo effects.

  9. 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.

  10. Lymphangiogenesis by blind-ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting.

    Science.gov (United States)

    Parsons-Wingerter, Patricia; McKay, Terri L; Leontiev, Dmitry; Vickerman, Mary B; Condrich, Terence K; Dicorleto, Paul E

    2006-03-01

    Development of effective vascular therapies requires the understanding of all modes of vessel formation involved in angiogenesis (here termed "hemangiogenesis") and lymphangiogenesis. Two major modes of vessel morphogenesis include sprouting of a new vessel from a preexisting vessel and splitting of a preexisting parent vessel into two offspring vessels. In the quail chorioallantoic membrane (CAM) during mid-development (embryonic days E6-E9), lymphangiogenesis progressed primarily via blind-ended vessel sprouting. Isolated lymphatic endothelial progenitor cells were recruited to the tips of growing vessels. During concurrent hemangiogenesis, parent blood vessels expanded from the capillary network and split into offspring vessels, accompanied by transient capillary expression of alpha smooth muscle actin (alphaSMA) and recruitment of polarized mural progenitor cells. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptor VEGFR-2, alphaSMA (specific to CAM blood vessels), homeobox transcription factor Prox1 (specific to lymphatics), and the quail hematopoetic marker, QH-1. VEGFR-2 was expressed intensely in isolated cells and lymphatics, and moderately in blood vessels. Prox1 was absent from isolated progenitor cells prior to lymphatic recruitment. Exogenous vascular endothelial growth factor-165 (VEGF165) increased blood vessel density and anastomotic frequency without changing endogenous modes of vascular/lymphatic vessel formation or marker expression. Although VEGF165 is a key cellular regulator of hemangiogenesis and vasculogenesis, the role of VEGF165 in lymphangiogenesis is less clear. Interestingly, VEGF165 increased lymphatic vessel diameter and density as measured by novel Euclidean distance mapping, and the antimaturational dissociation of lymphatics from blood vessels, accompanied by lymphatic reassociation into homogeneous networks.

  11. 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.

  12. By Different Cellular Mechanisms, Lymphatic Vessels Sprout by Endothelial Cell Recruitment Whereas Blood Vessels Grow by Vascular Expansion

    Science.gov (United States)

    Parsons-Wingerter, Patricia; McKay, Terri L.; Leontiev, Dmitry; Condrich, Terence K.; DiCorleto, Paul E.

    2005-01-01

    The development of effective vascular therapies requires the understanding of all modes of vessel formation contributing to vasculogenesis, angiogenesis (here termed hemangiogenesis) and lymphangiogenesis. We show that lymphangiogenesis proceeds by blind-ended vessel sprouting via recruitment of isolated endothelial progenitor cells to the tips of growing vessels, whereas hemangiogenesis occurs by non-sprouting vessel expansion from the capillary network, during middevelopment in the quail chorioallantoic membrane (CAM). Blood vessels expanded out of capillaries that displayed transient expression of alpha smooth muscle actin (alphaSMA), accompanied by mural recruitment of migratory progenitor cells expressing SMA. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptors VEGFR-1 and VEGFR-2, alphaSMA (expressed on CAM blood vessels but not on lymphatics), homeobox transcription factor Prox-1 (specific to CAM lymphatic endothelium), and the quail hematopoetic/vascular marker, QH-1. Expression of VEGFR-1 was highly restricted to blood vessels (primarily capillaries). VEGFR-2 was expressed intensely in isolated hematopoietic cells, lymphatic vessels and moderately in blood vessels. Prox-1 was absent from endothelial progenitor cells prior to lymphatic recruitment. Although vascular endothelial growth factor-165 (VEGF(sub 165)) is a key regulator of numerous cellular processes in hemangiogenesis and vasculogenesis, the role of VEGF(sub 165) in lymphangiogenesis is less clear. Exogenous VEGF(sub 165) increased blood vessel density without changing endogenous modes of vascular/lymphatic vessel formation or marker expression patterns. However, VEGF(sub 165) did increase the frequency of blood vascular anastomoses and strongly induced the antimaturational dissociation of lymphatics from blood vessels, with frequent formation of homogeneous lymphatic networks.

  13. Promotion of adhesion and proliferation of endothelial progenitor cells on decellularized valves by covalent incorporation of RGD peptide and VEGF.

    Science.gov (United States)

    Zhou, Jianliang; Ding, Jingli; Nie, Bin'en; Hu, Shidong; Zhu, Zhigang; Chen, Jia; Xu, Jianjun; Shi, Jiawei; Dong, Nianguo

    2016-09-01

    Tissue engineered heart valve is a promising alternative to current heart valve surgery, for its capability of growth, repair, and remodeling. However, extensive development is needed to ensure tissue compatibility, durability and antithrombotic potential. This study aims to investigate the biological effects of multi-signal composite material of polyethyl glycol-cross-linked decellularized valve on adhesion and proliferation of endothelial progenitor cells. Group A to E was decellularized valve leaflets, composite material of polyethyl glycol-cross-linked decellularized valves leaflets, vascular endothelial growth factor-composite materials, Arg-Gly-Asp peptide-composite materials and multi-signal modified materials of polyethyl glycol-cross-linked decellularized valve leaflets, respectively. The endothelial progenitor cells were seeded for each group, cell adhesion and proliferation were detected and neo-endothelium antithrombotic function of the multi-signal composite materials was evaluated. At 2, 4, and 8 h after the seeding, the cell numbers and 3H-TdR incorporation in group D were the highest. At 2, 4, and 8 days after the seeding, the cell numbers and 3H-TdR incorporation were significantly higher in groups C, D, and E compared with groups A and B (P composite material of PEG-crosslinked decellularized valve leaflets synergistically promoted the adhesion and proliferation of endothelial progenitor cells on the composite material, which may help in tissue engineering of heart valves.

  14. Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.

    Science.gov (United States)

    Ardehali, Reza; Ali, Shah R; Inlay, Matthew A; Abilez, Oscar J; Chen, Michael Q; Blauwkamp, Timothy A; Yazawa, Masayuki; Gong, Yongquan; Nusse, Roeland; Drukker, Micha; Weissman, Irving L

    2013-02-26

    A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2(+) cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.

  15. Lost circulation technology development status

    Energy Technology Data Exchange (ETDEWEB)

    Glowka, D.A.; Schafer, D.M.; Loeppke, G.E.; Scott, D.D.; Wernig, M.D.; Wright, E.K.

    1992-07-01

    Lost circulation is the loss of drilling fluid from the wellbore to fractures or pores in the rock formation. In geothermal drilling, lost circulation is often a serious problem that contributes greatly to the cost of the average geothermal well. The Lost Circulation Technology Development Program is sponsored at Sandia National Laboratories by the US Department of Energy. The goal of the program is to reduce lost circulation costs by 30--50% through the development of mitigation and characterization technology. This paper describes the technical progress made in this program during the period April 1991--March 1992. 8 refs.

  16. 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.

  17. Acute management of vascular air embolism

    Directory of Open Access Journals (Sweden)

    Shaikh Nissar

    2009-01-01

    Full Text Available Vascular air embolism (VAE is known since early nineteenth century. It is the entrainment of air or gas from operative field or other communications into the venous or arterial vasculature. Exact incidence of VAE is difficult to estimate. High risk surgeries for VAE are sitting position and posterior fossa neurosurgeries, cesarean section, laparoscopic, orthopedic, surgeries invasive procedures, pulmonary overpressure syndrome, and decompression syndrome. Risk factors for VAE are operative site 5 cm  above the heart, creation of pressure gradient which will facilitate entry of air into the circulation, orogenital sex during pregnancy, rapid ascent in scuba (self contained underwater breathing apparatus divers and barotrauma or chest trauma. Large bolus of air can lead to right ventricular air lock and immediate fatality. In up to 35% patient, the foramen ovale is patent which can cause paradoxical arterial air embolism. VAE affects cardiovascular, pulmonary and central nervous system. High index of clinical suspicion is must to diagnose VAE. The transesophgeal echocardiography is the most sensitive device which will detect smallest amount of air in the circulation. Treatment of VAE is to prevent further entrainment of air, reduce the volume of air entrained and haemodynamic support. Mortality of VAE ranges from 48 to 80%. VAE can be prevented significantly by proper positioning during surgery, optimal hydration, avoiding use of nitrous oxide, meticulous care during insertion, removal of central venous catheter, proper guidance, and training of scuba divers.

  18. 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.

  19. 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.

  20. Postmortem circulation: a new model for testing endovascular devices and training clinicians in their use.

    Science.gov (United States)

    Chevallier, Christine; Willaert, Wouter; Kawa, Emilia; Centola, Marcos; Steger, Beat; Dirnhofer, Richard; Mangin, Patrice; Grabherr, Silke

    2014-05-01

    The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients.

  1. New approaches to SNe Ia progenitors

    CERN Document Server

    Ruiz-Lapuente, Pilar

    2014-01-01

    Although Type Ia supernovae (SNe Ia) are a major tool in cosmology and play a key role in the chemical evolution of galaxies, the nature of their progenitor systems (apart from the fact that they must be close binaries containing at least one white dwarf) remains largely unknown. In the last decade, considerable efforts have been made, both observationally and theoretically, to solve this problem. Observations have, however, revealed a previously unsuspected variety of events, ranging from very underluminous outbursts to clearly overluminous ones, and spanning a range well outside the peak luminosity--decline rate of the light curve relationship, used to make calibrated candles of the SNe Ia. On the theoretical side, new explosion scenarios, such as violent mergings of pairs of white dwarfs, have been explored. We review those recent developments, emphasizing the new observational findings, but also trying to tie them to the different scenarios and explosion mechanisms proposed thus far.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, P L; Pedersen-Bjergaard, U; Schalkwijk, C

    2010-01-01

    OBJECTIVE: Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe...... levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes....

  7. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-01-10

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  8. 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.

  9. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction.

    Science.gov (United States)

    Xu, Jiajun; Yang, Ming; Kosterin, Paul; Salzberg, Brian M; Milovanova, Tatyana N; Bhopale, Veena M; Thom, Stephen R

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries.

  10. 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

  11. 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.

  12. The peritoneum as a natural scaffold for vascular regeneration.

    Directory of Open Access Journals (Sweden)

    Stefano Bonvini

    Full Text Available OBJECTIVE: The peritoneum has the same developmental origin as blood vessels, is highly reactive and poorly thrombogenic. We hypothesize that parietal peritoneum can sustain development and regeneration of new vessels. METHODS AND RESULTS: The study comprised two experimental approaches. First, to test surgical feasibility and efficacy of the peritoneal vascular autograft, we set up an autologous transplantation procedure in pigs, where a tubularized parietal peritoneal graft was covered with a metal mesh and anastomosed end-to-end in the infrarenal aorta. Second, to dissect the contribution of graft vs host cells to the newly developed vessel wall, we performed human-to-rat peritoneal patch grafting in the abdominal aorta and examined the origin of endothelial and smooth muscle cells. In pig experiments, the graft remodeled to an apparently normal blood vessel, without thrombosis. Histology confirmed arterialization of the graft with complete endothelial coverage and neointimal hyperplasia in the absence of erosion, inflammation or thrombosis. In rats, immunostaining for human mitochondri revealed that endothelial cells and smooth muscle cells rarely were of human origin. Remodeling of the graft was mainly attributable to local cells with no clear evidence of c-kit+ endothelial progenitor cells or c-kit+ resident perivascular progenitor cells. CONCLUSIONS: The parietal peritoneum can be feasibly used as a scaffold to sustain the regeneration of blood vessels, which appears to occur through the contribution of host-derived resident mature cells.

  13. 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.

  14. 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...

  15. Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation.

    Science.gov (United States)

    Garriock, Robert J; Chalamalasetty, Ravindra B; Kennedy, Mark W; Canizales, Lauren C; Lewandoski, Mark; Yamaguchi, Terry P

    2015-05-01

    In the development of the vertebrate body plan, Wnt3a is thought to promote the formation of paraxial mesodermal progenitors (PMPs) of the trunk region while suppressing neural specification. Recent lineage-tracing experiments have demonstrated that these trunk neural progenitors and PMPs derive from a common multipotent progenitor called the neuromesodermal progenitor (NMP). NMPs are known to reside in the anterior primitive streak (PS) region; however, the extent to which NMPs populate the PS and contribute to the vertebrate body plan, and the precise role that Wnt3a plays in regulating NMP self-renewal and differentiation are unclear. To address this, we used cell-specific markers (Sox2 and T) and tamoxifen-induced Cre recombinase-based lineage tracing to locate putative NMPs in vivo. We provide functional evidence for NMP location primarily in the epithelial PS, and to a lesser degree in the ingressed PS. Lineage-tracing studies in Wnt3a/β-catenin signaling pathway mutants provide genetic evidence that trunk progenitors normally fated to enter the mesodermal germ layer can be redirected towards the neural lineage. These data, combined with previous PS lineage-tracing studies, support a model that epithelial anterior PS cells are Sox2(+)T(+) multipotent NMPs and form the bulk of neural progenitors and PMPs of the posterior trunk region. Finally, we find that Wnt3a/β-catenin signaling directs trunk progenitors towards PMP fates; however, our data also suggest that Wnt3a positively supports a progenitor state for both mesodermal and neural progenitors.

  16. 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 ...

  17. The vascular secret of Klotho

    DEFF Research Database (Denmark)

    Lewin, Ewa; Olgaard, Klaus

    2015-01-01

    Klotho is an evolutionarily highly conserved protein related to longevity. Increasing evidence of a vascular protecting effect of the Klotho protein has emerged and might be important for future treatments of uremic vascular calcification. It is still disputed whether Klotho is locally expressed ...

  18. Vascularity in the reptilian spectacle.

    Science.gov (United States)

    Mead, A W

    1976-07-01

    Vascularization of the spectacle or brille of the reptile was demonstrated by biomicroscopy, histology, fluorescein (in vivo), and Microfil silicone rubber (in situ) injections. This unusual vascularity provides new evidence for reassessment of the origin and development of this structure, and a useful tool with which to do so.

  19. 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.

  20. 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

  1. TNFα-Damaged-HUVECs Microparticles Modify Endothelial Progenitor Cell Functional Activity

    Science.gov (United States)

    Luna, Carlos; Carmona, Andrés; Alique, Matilde; Carracedo, Julia; Ramirez, Rafael

    2015-01-01

    Endothelial progenitor cells (EPCs) have an important role in the maintenance of vascular integrity and homeostasis. While there are many studies that explain EPCs mechanisms action, there are few studies that demonstrate how they interact with other emerging physiological elements such as Endothelial Microparticles (EMPs). EMPs are membranous structures with a size between 100 and 1000 nm that act as molecular information transporter in biological systems and are known as an important elements in develop different pathologies; moreover a lot of works explains that are novel biomarkers. To elucidate these interactions, we proposed an in vitro model of endothelial damage mediated by TNFalpha, in which damaged EMPs and EPCs are in contact to assess EPCs functional effects. We have observed that damaged EMPs can modulate several EPCs classic factors as colony forming units (CFUs), contribution to repair a physically damaged endothelium (wound healing), binding to mature endothelium, and co-adjuvants to the formation of new vessels in vitro (angiogenesis). All of these in a dose-dependent manner. Damaged EMPs at a concentration of 103 MPs/ml have an activating effect of these capabilities, while at concentrations of 105 MPs/ml these effects are attenuated or reduced. This in vitro model helps explain that in diseases where there is an imbalance between these two elements (EPCs and damaged EMPs), the key cellular elements in the regeneration and maintenance of vascular homeostasis (EPCs) are not fully functional, and could explain, at least in part, endothelial dysfunction associated in various pathologies. PMID:26733886

  2. Strategies to stimulate mobilization and homing of endogenous stem and progenitor cells for bone tissue repair

    Directory of Open Access Journals (Sweden)

    Marietta eHerrmann

    2015-06-01

    Full Text Available The gold standard for the treatment of critical sized bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies represent an alternative approach. Mesenchymal stem cells (MSCs have been considered as a source of osteoprogenitor cells. More recently, focus has been placed on the use of endothelial progenitor cells (EPCs, since vascularization is a critical step in bone healing. Although many of these approaches have demonstrated effectiveness for bone regeneration, cell-based therapies require time consuming and cost expensive in vitro cell expansion procedures. Accordingly, research is becoming increasingly focused on the homing and stimulation of native cells. The stromal cell-derived factor 1 (SDF-1 – CXCR4 axis has been shown to be critical for the recruitment of MSCs and EPCs. Vascular endothelial growth factor (VEGF is a key factor in angiogenesis and has been targeted in many studies. Here, we present an overview of the different approaches for delivering homing factors to the defect site by absorption or incorporation to biomaterials, gene therapy or via genetically manipulated cells. We further review strategies focusing on the stimulation of endogenous cells to support bone repair. Finally, we discuss the major challenges in the treatment of critical size bone defects and fracture non-unions.

  3. 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.

  4. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    Science.gov (United States)

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    hair. The viability of the compact bone, bone marrow and skin at 100 days posttransplant was confirmed by histologic evaluation, and bone marrow revealed active hematopoiesis. Bilateral skin/bone transplantation model may serve as an experimental tool to study new strategies in tolerance induction by altering the amount of the immunogenic load in the form of skin transplant and bone marrow delivery in the vascularized form, allowing for expedited engraftment of stem and progenitor cells.

  5. Caffeine's Vascular Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2010-01-01

    Full Text Available Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial.

  6. Maintenance of vascular integrity by pericytes is essential for normal kidney function.

    Science.gov (United States)

    Lemos, Dario R; Marsh, Graham; Huang, Angela; Campanholle, Gabriela; Aburatani, Takahide; Dang, Lan; Gomez, Ivan; Fisher, Ken; Ligresti, Giovanni; Peti-Peterdi, Janos; Duffield, Jeremy S

    2016-12-01

    Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

  7. Citicoline in vascular cognitive impairment and vascular dementia after stroke.

    Science.gov (United States)

    Alvarez-Sabín, Jose; Román, Gustavo C

    2011-01-01

    Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.

  8. 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 $...

  9. Luminal progenitors restrict their lineage potential during mammary gland development.

    Directory of Open Access Journals (Sweden)

    Veronica Rodilla

    2015-02-01

    Full Text Available The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  10. Luminal progenitors restrict their lineage potential during mammary gland development.

    Science.gov (United States)

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  11. 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.

  12. 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...

  13. 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.

  14. 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

  15. 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

  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. Transplanted progenitors generate functional enteric neurons in the postnatal colon

    OpenAIRE

    2013-01-01

    Cell therapy has the potential to treat gastrointestinal motility disorders caused by diseases of the enteric nervous system. Many studies have demonstrated that various stem/progenitor cells can give rise to functional neurons in the embryonic gut; however, it is not yet known whether transplanted neural progenitor cells can migrate, proliferate, and generate functional neurons in the postnatal bowel in vivo. We transplanted neurospheres generated from fetal and postnatal intestinal neural c...

  18. 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

  19. Mechanisms of oxidative stress and vascular dysfunction

    Science.gov (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J

    2003-01-01

    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  20. 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.

  1. 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

  2. A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Richard Longeras

    2012-01-01

    Full Text Available Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs. Pigment epithelium-derived factor (PEDF contains an N-terminal 34-amino acid peptide (PEDF-34 that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+ cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS. OIR significantly increased the number of circulating Tie2-GFP+ at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+ cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+ cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.

  3. On the progenitor of the Type IIb supernova 2016gkg

    Science.gov (United States)

    Kilpatrick, Charles D.; Foley, Ryan J.; Abramson, Louis E.; Pan, Yen-Chen; Lu, Cicero-Xinyu; Williams, Peter; Treu, Tommaso; Siebert, Matthew R.; Fassnacht, Christopher D.; Max, Claire E.

    2017-03-01

    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 0.89σ. The HST photometry is consistent with the progenitor star being an A0 Ia star with T = 9500 K and log (L/L⊙) = 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 d 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 2016 September 20.15 and progenitor-star radius of log (R/R⊙) = 2.41, which agrees with photometry from the progenitor star. Our findings are also consistent with detections of other SNe IIb progenitor stars, although more luminous and bluer than most other examples.

  4. 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.

  5. Hematopoietic progenitor cell mobilization for autologous transplantation - a literature review

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Salvino

    2016-02-01

    Full Text Available ABSTRACT The use of high-dose chemotherapy with autologous support of hematopoietic progenitor cells is an effective strategy to treat various hematologic neoplasms, such as non-Hodgkin lymphomas and multiple myeloma. Mobilized peripheral blood progenitor cells are the main source of support for autologous transplants, and collection of an adequate number of hematopoietic progenitor cells is a critical step in the autologous transplant procedure. Traditional strategies, based on the use of growth factors with or without chemotherapy, have limitations even when remobilizations are performed. Granulocyte colony-stimulating factor is the most widely used agent for progenitor cell mobilization. The association of plerixafor, a C-X-C Chemokine receptor type 4 (CXCR4 inhibitor, to granulocyte colony stimulating factor generates rapid mobilization of hematopoietic progenitor cells. A literature review was performed of randomized studies comparing different mobilization schemes in the treatment of multiple myeloma and lymphomas to analyze their limitations and effectiveness in hematopoietic progenitor cell mobilization for autologous transplant. This analysis showed that the addition of plerixafor to granulocyte colony stimulating factor is well tolerated and results in a greater proportion of patients with non-Hodgkin lymphomas or multiple myeloma reaching optimal CD34+ cell collections with a smaller number of apheresis compared the use of granulocyte colony stimulating factor alone.

  6. Interstitial stromal progenitors during kidney development: here, there and everywhere.

    Science.gov (United States)

    Fanni, Daniela; Gerosa, Clara; Vinci, Laura; Ambu, Rossano; Dessì, Angelica; Eyken, Peter Van; Fanos, Vassilios; Faa, Gavino

    2016-12-01

    In recent years, the renal interstitium has been identified as the site of multiple cell types, giving rise to multiple contiguous cellular networks with multiple fundamental structural and functional roles. Few studies have been carried out on the morphological and functional properties of the stromal/interstitial renal cells during the intrauterine life. This work was aimed at reviewing the peculiar features of renal interstitial stem/progenitor cells involved in kidney development. The origin of the renal interstitial progenitor cells remains unknown. During kidney development, besides the Six2 + cells of the cap mesenchyme, a self-renewing progenitor population, characterized by the expression of Foxd1, represents the first actor of the non-nephrogenic lineage. Foxd1 + interstitial progenitors originate the cortical and the renal medullary interstitial progenitors. Here, the most important stromal/interstitial compartments present in the developing human kidney will be analyzed: capsular stromal cells, cortical interstitial cells, medullary interstitial cells, the interstitium inside the renal stem cell niche, Hilar interstitial cells and Ureteric interstitial cells. Data reported here indicate that the different interstitial compartments of the developing kidney are formed by different cell types that characterize the different renal areas. Further studies are needed to better characterize the different pools of renal interstitial progenitors and their role in human nephrogenesis.

  7. 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

  8. Boosting Hematopoietic Engraftment after in Utero Transplantation through Vascular Niche Manipulation

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    Saloomeh Mokhtari

    2016-06-01

    Full Text Available 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.

  9. Constraining GRB progenitors environment with Swift XRT

    CERN Document Server

    Saez, Dounia

    2015-01-01

    The characteristics of the Gamma-Ray Bursts (GRBs) environment may reflect the differences in GRB progenitors: long GRBs are expected to be found in high-density star-forming regions of the GRB host galaxies, while short ones may be associated with an older stellar population that may have had the time to travel far from stellar forming regions in potentially lower density regions. The latter is related to the hypothesis that short GRBs are associated to the merging of compact objects (BH-NS or NS-NS). We used the Swift XRT GRB afterglow archive to compare the intrinsic neutral hydrogen column density values for long and short GRBs within the redshift range 0.1- 1.3, performing a coherent analysis, and excluding from our analysis observations with poor statistics, which reduced our sample to 15 short GRBs. While short GRBs effectively show a median absorption value smaller than long ones the result is not statistically significant. In order to increase our sample we added short GRBs without redshift measure, ...

  10. 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...

  11. The Binary Progenitor of Tycho Brahe's Supernova

    Science.gov (United States)

    Ruiz-Lapuente, P.

    2006-08-01

    The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova (SN 1572) provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.

  12. 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...

  13. 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.

  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. Harmine stimulates proliferation of human neural progenitors

    Science.gov (United States)

    Dakic, Vanja; Maciel, Renata de Moraes; Drummond, Hannah; Nascimento, Juliana M.; Trindade, Pablo

    2016-01-01

    Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo. PMID:27957390

  16. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  17. [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.

  18. 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 durin...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress.......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...

  19. 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.

  20. Ion channels and transporters as therapeutic targets in the pulmonary circulation.

    Science.gov (United States)

    Olschewski, Andrea; Papp, Rita; Nagaraj, Chandran; Olschewski, Horst

    2014-12-01

    Pulmonary circulation is a low pressure, low resistance, high flow system. The low resting vascular tone is maintained by the concerted action of ion channels, exchangers and pumps. Under physiological as well as pathophysiological conditions, they are targets of locally secreted or circulating vasodilators and/or vasoconstrictors, leading to changes in expression or to posttranslational modifications. Both structural changes in the pulmonary arteries and a sustained increase in pulmonary vascular tone result in pulmonary vascular remodeling contributing to morbidity and mortality in pediatric and adult patients. There is increasing evidence demonstrating the pivotal role of ion channels such as K(+) and Cl(-) or transient receptor potential channels in different cell types which are thought to play a key role in vasoconstrictive remodeling. This review focuses on ion channels, exchangers and pumps in the pulmonary circulation and summarizes their putative pathophysiological as well as therapeutic role in pulmonary vascular remodeling. A better understanding of the mechanisms of their actions may allow for the development of new options for attenuating acute and chronic pulmonary vasoconstriction and remodeling treating the devastating disease pulmonary hypertension.

  1. 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.

  2. 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.

  3. 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.

  4. [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.

  5. Vascular injuries during gynecological laparoscopy: the vascular surgeon's advice

    Directory of Open Access Journals (Sweden)

    Marcello Barbosa Barros

    Full Text Available CONTEXT: Iatrogenic vascular problems due to laparoscopy are a well recognized problem and lead to significant repercussions. In this context, a ten-year review of cases topic is presented, based on experience gained while heading two important vascular surgery services. CASES: Five patients with vascular injuries during elective laparoscopy are described. These patients presented with seven lesions of iliac vessels. All cases were evaluated immediately and required laparotomy, provisional hemostasis and urgent attendance by a vascular surgeon. Direct suturing was performed in three cases. One aortoiliac bypass and one ilioiliac reversed venous graft were made. Venous lesions were sutured. One case of a point-like perforation of the small bowel was found. There were no deaths and no complications during the postoperative period. DISCUSSION: Important points on this subject are made, and advice is given. There needs to be immediate recognition of the vascular injury, and expert repair by a vascular surgeon is recommended, in order to significantly reduce the degree of complications.

  6. Does macrophage migration factor function as a switch in septic circulation crisis?

    Directory of Open Access Journals (Sweden)

    Dr. Li Ma

    2008-07-01

    Full Text Available Circulation dysfunction-associated mortality is defined as its reduced responsiveness to circulation active agents in the pathological context of sepsis/septic shock. Macrophage migration inhibitory factor (MIF, a versatile pro-inflammatory cytokine, has been identified independently from other mediators and found to play certain roles in the “bio-vicious-gate” of circulation collapse. Cumulating evidence shows that MIF exerts its function through interaction with a body of signal molecules that are involved in functional regulation of several end-point molecules such as, carbon monoxide, insulin, complement C5a, nitric oxide, inducible nitric oxide synthase, and glucocorticoids, and these downstream mediators are linked to vascular tone differentially. Thus, MIF stays as a molecular switch at the signaling upstream to charge the downstream action of signals in sepsis-associated circulation crisis.

  7. Cell-Surface Protein Profiling Identifies Distinctive Markers of Progenitor Cells in Human Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Akiyoshi Uezumi

    2016-08-01

    Full Text Available Skeletal muscle contains two distinct stem/progenitor populations. One is the satellite cell, which acts as a muscle stem cell, and the other is the mesenchymal progenitor, which contributes to muscle pathogeneses such as fat infiltration and fibrosis. Detailed and accurate characterization of these progenitors in humans remains elusive. Here, we performed comprehensive cell-surface protein profiling of the two progenitor populations residing in human skeletal muscle and identified three previously unrecognized markers: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers distinguish myogenic and mesenchymal progenitors, and enable efficient isolation of the two types of progenitors. Functional study revealed that CD82 ensures expansion and preservation of myogenic progenitors by suppressing excessive differentiation, and CD201 signaling favors adipogenesis of mesenchymal progenitors. Thus, cell-surface proteins identified here are not only useful markers but also functionally important molecules, and provide valuable insight into human muscle biology and diseases.

  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. 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.

  10. Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells.

    Science.gov (United States)

    Vela, José M; Molina-Holgado, Eduardo; Arévalo-Martín, Angel; Almazán, Guillermina; Guaza, Carmen

    2002-07-01

    Interleukin-1 (IL-1) is a pleiotropic cytokine expressed during normal CNS development and in inflammatory demyelinating diseases, but remarkably little is known about its effect on oligodendroglial cells. In this study we explored the role of IL-1beta in oligodendrocyte progenitors and differentiated oligodendrocytes. The effects of IL-1beta were compared to those of IL-1 receptor antagonist, the specific inhibitor of IL-1 activity, since progenitors and differentiated oligodendrocytes produce IL-1beta and express IL-1 receptors. Unlike other proinflammatory cytokines (TNFalpha and IFNgamma), IL-1beta was not toxic for oligodendrocyte lineage cells. However, this cytokine inhibited proliferation of oligodendrocyte progenitors in the presence of growth factors (PDGF plus bFGF). This was evidenced by a significant decrease in both cells incorporating bromodeoxyuridine (45%) and total cell numbers (57%) after 6 days of treatment. Interestingly, IL-1beta blocked proliferation at the late progenitor/prooligodendrocyte (O4+) stage but did not affect proliferation of early progenitors (A2B5+). Inhibition of proliferation paralleled with promotion of differentiation, as revealed by the increased percentage of R-mab+ cells (6.7-fold). Moreover, when oligodendrocyte progenitors were allowed to differentiate in the absence of growth factors, treatment with IL-1beta promoted maturation to the MBP+ stage (4.2-fold) and survival of differentiating oligodendrocytes (2.1-fold). Regarding intracellular signaling, IL-1beta activated the p38 mitogen-activated protein kinase (MAPK) but not the p42/p44 MAPK and, when combined with growth factors, intensified p38 activation but inhibited the growth-factor-induced p42/p44 activation. IL-1beta also induced a time-dependent inhibition of PFGF-Ralpha gene expression. These results support a role for IL-1beta in promoting mitotic arrest and differentiation of oligodendrocyte progenitors as well as maturation and survival of differentiating

  11. Endothelial progenitor cells and integrins: adhesive needs

    Directory of Open Access Journals (Sweden)

    Caiado Francisco

    2012-03-01

    Full Text Available Abstract In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  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. Generation of neuronal progenitor cells in response to tumors in the human brain.

    Science.gov (United States)

    Macas, Jadranka; Ku, Min-Chi; Nern, Christian; Xu, Yuanzhi; Bühler, Helmut; Remke, Marc; Synowitz, Michael; Franz, Kea; Seifert, Volker; Plate, Karl H; Kettenmann, Helmut; Glass, Rainer; Momma, Stefan

    2014-01-01

    Data from transgenic mouse models show that neuronal progenitor cells (NPCs) migrate toward experimental brain tumors and modulate the course of pathology. However, the pathways whereby NPCs are attracted to CNS neoplasms are not fully understood and it is unexplored if NPCs migrate toward brain tumors (high-grade astrocytomas) in humans. We analyzed the tumor-parenchyma interface of neurosurgical resections for the presence of (NPCs) and distinguished these physiological cells from the tumor mass. We observed that polysialic acid neural cell adhesion molecule-positive NPCs accumulate at the border of high-grade astrocytomas and display a marker profile consistent with immature migratory NPCs. Importantly, these high-grade astrocytoma-associated NPCs did not carry genetic aberrations that are indicative of the tumor. Additionally, we observed NPCs accumulating in CNS metastases. These metastatic tumors are distinguished from neural cells by defined sets of markers. Transplanting murine glioma cells embedded in a cell-impermeable hollow fiber capsule into the brains of nestin-gfp reporter mice showed that diffusible factors are sufficient to induce a neurogenic reaction. In vitro, vascular endothelial growth factor (VEGF) secreted from glioma cells increases the migratory and proliferative behavior of adult human brain-derived neural stem and progenitor cells via stimulation of VEGF receptor-2 (VEGFR-2). In vivo, inhibiting VEGFR-2 signaling with a function-blocking antibody led to a reduction in NPC migration toward tumors. Overall, our data reveal a mechanism by which NPCs are attracted to CNS tumors and suggest that NPCs accumulate in human high-grade astrocytomas.

  19. 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.

  20. Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players.

    Science.gov (United States)

    Alexandru, Nicoleta; Badila, Elisabeta; Weiss, Emma; Cochior, Daniel; Stępień, Ewa; Georgescu, Adriana

    2016-03-25

    The recognition of the importance of diabetes in vascular disease has greatly increased lately. Common risk factors for diabetes-related vascular disease include hyperglycemia, insulin resistance, dyslipidemia, inflammation, hypercoagulability, hypertension, and atherosclerosis. All of these factors contribute to the endothelial dysfunction which generates the diabetic complications, both macro and microvascular. Knowledge of diabetes-related vascular complications and of associated mechanisms it is becoming increasingly important for therapists. The discovery of microparticles (MPs) and their associated microRNAs (miRNAs) have opened new perspectives capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers. MPs known as submicron vesicles generated from membranes of apoptotic or activated cells into circulation have the ability to act as autocrine and paracrine effectors in cell-to-cell communication. They operate as biological vectors modulating the endothelial dysfunction, inflammation, coagulation, angiogenesis, thrombosis, subsequently contributing to the progression of macro and microvascular complications in diabetes. More recently, miRNAs have started to be actively investigated, leading to first exciting reports, which suggest their significant role in vascular physiology and disease. The contribution of MPs and also of their associated miRNAs to the development of vascular complications in diabetes was largely unexplored and undiscussed. In essence, with this review we bring light upon the understanding of impact diabetes has on vascular biology, and the significant role of MPs and MPs associated miRNAs as novel mediators, potential biomarkers and therapeutic targets in vascular complications in diabetes.

  1. Perioperative iloprost and endothelial progenitor cells in uremic patients with severe limb ischemia undergoing peripheral revascularization.

    Science.gov (United States)

    Coppolino, Giuseppe; Buemi, Antoine; Bolignano, Davide; Lacquaniti, Antonio; La Spada, Michele; Stilo, Francesco; De Caridi, Giovanni; Benedetto, Francesco; Loddo, Saverio; Buemi, Michele; Spinelli, Francesco

    2009-11-01

    The incidence of severe limb ischemia (SLI) is high among haemodialysis (HD) patients. Limb rescue rate after surgical revascularization is relatively poor compared with patients with normal renal function. Prostanoids are an interesting category as adjuvants to revascularization. New vessel growth develops not exclusively by proliferation of endothelial cells in vascular extremities but also by cells mobilized from the bone marrow (HSC), transformed into endothelial progenitor cells (EPC) contributing to both re-endothelialization and neovascularization. Basal number of HSC and EPC is significantly reduced in HD patients and correlated with a subsequent defective neovascularization. The aim of this study was to evaluate the effects of perioperative treatment with iloprost in uremic patients with acute ischemia of lower limbs, undergoing surgical revascularization, on endothelial progenitor cells, hypothesizing a possible biological mechanism induced by the prostanoids. A search was also made for vascular remodeling processes through the analysis of the concentrations of soluble adhesion molecules (i-CAM, v-CAM, e-selectin), biochemical markers of endothelial activation. Thirty HD patients with SLI undergoing peripheral revascularization were enrolled (15 were treated with iloprost and 15 with a placebo). Iloprost was administered as an intra-arterial bolus of 3000 ng over 1 to 3 min immediately after revascularization and in the same affected artery. Serum samples were taken before revascularization (T0), at 6 (T6) and 24 h (T24) after infusion to measure sICAM-1, sE-selectin, and sVCAM-1, and for quantification of HSC and EPC. Progenitors were identified by specific surface markers CD34+, CD133+ and VEGFR2+. Count was conducted using PROCOUNT performed in a TRUCOUNT tube and with a FACSort flow cytometer. Before revascularization, all patients showed a decreased number of HSC and EPC. After 6 h, HSC augmented significantly compared with T0 in both groups. The

  2. The Progenitor of the Type IIb SN 2008ax Revisited

    CERN Document Server

    Folatelli, Gastón; Kuncarayakti, Hanindyo; Benvenuto, Omar G; Maeda, Keiichi; Nomoto, Ken'ichi

    2015-01-01

    Hubble Space Telescope observations of the site of the supernova (SN) 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf-Rayet (WR) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modelling shows the pre-explosion mass was $4-5$ $M_\\odot$ and the radius was $30-50$ $R_\\odot$, wh...

  3. THE TYPE IIb SUPERNOVA 2011dh FROM A SUPERGIANT PROGENITOR

    Energy Technology Data Exchange (ETDEWEB)

    Bersten, Melina C.; Nomoto, Ken' ichi; Folatelli, Gaston; Maeda, Keiichi [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan); Benvenuto, Omar G. [Facultad de Ciencias Astronomicas y Geofisicas, Universidad Nacional de La Plata, Paseo del Bosque S/N, B1900FWA La Plata (Argentina); Ergon, Mattias; Sollerman, Jesper [The Oskar Klein Centre, Department of Astronomy, AlbaNova, SE-106 91 Stockholm (Sweden); Benetti, Stefano; Ochner, Paolo; Tomasella, Lina [INAF-Osservatorio Astronomico di Padova, Vicolo dell' Osservatorio 5, I-35122 Padova (Italy); Botticella, Maria Teresa [INAF-Osservatorio Astronomico di Capodimonte, Salita Moiariello 16, I-80131 Napoli (Italy); Fraser, Morgan; Kotak, Rubina, E-mail: melina.bersten@ipmu.jp [Astrophysics Research Centre, School of Mathematics and Physics, Queen' s University Belfast, Belfast BT7 1NN (United Kingdom)

    2012-09-20

    A set of hydrodynamical models based on stellar evolutionary progenitors is used to study the nature of SN 2011dh. Our modeling suggests that a large progenitor star-with R {approx} 200 R{sub Sun }-is needed to reproduce the early light curve (LC) of SN 2011dh. This is consistent with the suggestion that the yellow super-giant star detected at the location of the supernova (SN) in deep pre-explosion images is the progenitor star. From the main peak of the bolometric LC and expansion velocities, we constrain the mass of the ejecta to be Almost-Equal-To 2 M{sub Sun }, the explosion energy to be E = (6-10) Multiplication-Sign 10{sup 50} erg, and the {sup 56}Ni mass to be approximately 0.06 M{sub Sun }. The progenitor star was composed of a helium core of 3-4 M{sub Sun} and a thin hydrogen-rich envelope of Almost-Equal-To 0.1M{sub Sun} with a main-sequence mass estimated to be in the range of 12-15 M{sub Sun }. Our models rule out progenitors with helium-core masses larger than 8 M{sub Sun }, which correspond to M{sub ZAMS} {approx}> 25M{sub Sun }. This suggests that a single star evolutionary scenario for SN 2011dh is unlikely.

  4. The Type IIb Supernova 2011dh from a Supergiant Progenitor

    CERN Document Server

    Bersten, Melina C; Nomoto, Ken'ichi; Ergon, Mattias; Folatelli, Gastón; Sollerman, Jesper; Benetti, Stefano; Botticella, Maria Teresa; Fraser, Morgan; Kotak, Rubina; Maeda, Keiichi; Ochner, Paolo; Tomasella, Lina

    2012-01-01

    A set of hydrodynamical models based on stellar evolutionary progenitors is used to study the nature of SN 2011dh. Our modeling suggests that a large progenitor star ---with R ~200 Rsun---, is needed to reproduce the early light curve of SN 2011dh. This is consistent with the suggestion that the yellow super-giant star detected at the location of the SN in deep pre-explosion images is the progenitor star. From the main peak of the bolometric light curve and expansion velocities we constrain the mass of the ejecta to be ~2 Msun, the explosion energy to be E= 6-10 x 10^50 erg, and the 56Ni mass to be approximately 0.06 Msun. The progenitor star was composed of a helium core of 3 to 4 Msun and a thin hydrogen-rich envelope of ~0.1 M_sun with a main sequence mass estimated to be in the range of 12--15 Msun. Our models rule out progenitors with helium-core masses larger than 8 Msun, which correspond to M_ZAMS > 25 Msun. This suggests that a single star evolutionary scenario for SN 2011dh is unlikely.

  5. Type Ia Supernovae Keep Memory of their Progenitor Metallicity

    Science.gov (United States)

    Piersanti, Luciano; Bravo, Eduardo; Cristallo, Sergio; Domínguez, Inmaculada; Straniero, Oscar; Tornambé, Amedeo; Martínez-Pinedo, Gabriel

    2017-02-01

    The ultimate understanding of SNe Ia diversity is one of the most urgent issues to exploit thermonuclear explosions of accreted White Dwarfs (WDs) as cosmological yardsticks. In particular, we investigate the impact of the progenitor system metallicity on the physical and chemical properties of the WD at the explosion epoch. We analyze the evolution of CO WDs through the accretion and simmering phases by using evolutionary models based on time-dependent convective mixing and an extended nuclear network including the most important electron captures, beta decays, and URCA processes. We find that, due to URCA processes and electron-captures, the neutron excess and density at which the thermal runaway occurs are substantially larger than previously claimed. Moreover, we find that the higher the progenitor metallicity, the larger the neutron excess variation during the accretion and simmering phases and the higher the central density and the convective velocity at the explosion. Hence, the simmering phase acts as an amplifier of the differences existing in SNe Ia progenitors. When applying our results to the neutron excess estimated for the Tycho and Kepler young supernova remnants, we derive that the metallicity of the progenitors should be in the range Z=0.030{--}0.032, close to the average metallicity value of the thin disk of the Milky Way. As the amount of {}56{Ni} produced in the explosion depends on the neutron excess and central density at the thermal runaway, our results suggest that the light curve properties depend on the progenitor metallicity.

  6. The progenitor mass of the magnetar SGR1900+14

    CERN Document Server

    Davies, Ben; Kudritzki, Rolf-Peter; Trombley, Christine; Kouveliotou, Chryssa; Wachter, Stefanie

    2009-01-01

    Magnetars are young neutron stars with extreme magnetic fields (B > 10^{14}-10^{15}G). How these fields relate to the properties of their progenitor stars is not yet clearly established. However, from the few objects associated with young clusters it has been possible to estimate the initial masses of the progenitors, with results indicating that a very massive progenitor star (M_prog >40Msun) is required to produce a magnetar. Here we present adaptive-optics assisted Keck/NIRC2 imaging and Keck/NIRSPEC spectroscopy of the cluster associated with the magnetar SGR 1900+14, and report that the initial progenitor star mass of the magnetar was a factor of two lower than this limit, M_prog=17 \\pm 2 Msun. Our result presents a strong challenge to the concept that magnetars can only result from very massive progenitors. Instead, we favour a mechanism which is dependent on more than just initial stellar mass for the production of these extreme magnetic fields, such as the "fossil-field" model or a process involving c...

  7. Ex vivo expansion of human peripheral blood progenitors.

    Science.gov (United States)

    Chabannon, C; Herrera-Rodriguez, D; Bardin, F; Mouren, M; Novakovitch, G; Blaise, D; Maraninchi, D; Mannoni, P

    1995-01-01

    Culture of human hematopoietic progenitors on a large scale could lead to several clinical applications within the near future, including the production of differentiated and functional cells, the increase in the number of early progenitors, especially stem cells, with such use as gene transfer, or the improvement of grafts used to limit the hematological toxicity associated with high-dose chemotherapy. In this case, one can still distinguish different objectives: improvement of grafts that contain low numbers of progenitors because of prior chemotherapies or because of marrow involvement for example, and qualitative changes in the graft content that would allow to envision the disappearance, or the further reduction, in the duration of absolute neutropenia that follows delivery of high dose chemotherapy ("nadir rescue"), despite substitution of mobilized blood cells to marrow cells and the in vivo use of hematopoietic growth factors. Additional advantages may be related to tumor purging in autologous expanded cells, and to the change in the ratio between hematopoietic progenitors and immunocompetent cells in allogeneic expanded populations. Therefore it appears that in vitro expansion currently raises two types of questions: the first ones are related to the definition of clinical or biological endpoints to be achieved, the second ones are related to "bioengineering", and deal with the efficiency and safety of progenitor cell cultures to be used for clinical applications. We here present preliminary results preparing future pilot clinical studies with ex vivo cultured human hematopoietic cells.

  8. 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....

  9. 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.

  10. 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.

  11. Steroid hormones and the stroma-vascular cells of the adipose tissue.

    Science.gov (United States)

    Volat, Fanny; Bouloumié, Anne

    2013-09-01

    The stroma-vascular fraction (SVF) of adipose tissue (AT) is a heterogeneous cell fraction composed of progenitor cells, endothelial cells, and immune cells. SVF plays a key role in AT homeostasis and growth as well as in obesity-associated pathologies. The SVF cell composition and phenotype are distinct according to AT location and adiposity. Such discrepancies influence AT function and are involved in obesity-associated disorders such as chronic inflammation. Investigations performed in recent years in rodents and humans provided evidence that the stroma-vascular cells contribute to the conversion of steroid hormones in AT and are also steroid targets. This review describes the link between steroids and SVF depending on gender, adiposity, and AT location and highlights the potential role of sex and corticosteroid hormones in adipogenesis, angiogenesis, and their contributions in AT inflammation.

  12. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    Institute of Scientific and Technical Information of China (English)

    Donnahue; Dennie; Jean-Pierre; Louboutin; David; S; Strayer

    2016-01-01

    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 characterizethe 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 16mo 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 transduced by SV40vectors

  13. Effects of scuba diving on vascular repair mechanisms.

    Science.gov (United States)

    Culic, Vedrana Cikes; Van Craenenbroeck, Emeline; Muzinic, Nikolina Rezic; Ljubkovic, Marko; Marinovic, Jasna; Conraads, Viviane; Dujic, Zeljko

    2014-01-01

    A single air dive causes transient endothelial dysfunction. Endothelial progenitor cells (EPCs) and circulating angiogenic cells (CAC) contribute synergistically to endothelial repair. In this study (1) the acute effects of diving on EPC numbers and CAC migration and (2) the influence of the gas mixture (air/nitrox-36) was investigated. Ten divers performed two dives to 18 meters on Day (D) 1 and D3, using air. After 15 days, dives were repeated with nitrox-36. Blood sampling took place before and immediately after diving. Circulating EPCs were quantified by flow cytometry, CAC migration of culture was assessed on D7. When diving on air, a trend for reduced EPC numbers is observed post-dive, which is persistent on D1 and D3. CAC migration tends to improve acutely following diving. These effects are more pronounced with nitrox-36 dives. Diving acutely affects EPC numbers and CAC function, and to a larger extent when diving with nitrox-36. The diving-induced oxidative stress may influence recruitment or survival of EPC. The functional improvement of CAC could be a compensatory mechanism to maintain endothelial homeostasis.

  14. 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...

  15. Raised levels of circulating endothelial cells in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    N. Fracchiolla

    2011-09-01

    Full Text Available Objective: Circulating endothelial cells (CECs have been described in different conditions with vascular injury. Vascular abnormalities play a key role in the pathogenesis of Systemic Sclerosis (SSc. The aim of our study was to look for the presence of CECs in SSc patients and to evaluate their clinical significance. Methods: We studied 52 SSc patients and 40 healthy controls (HC. Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD31 and P1H12 positive, and activated CECs as CD45 negative and P1H12, CD62, or CD106 positive. Results: Total and activated CEC counts were significantly higher in SSc patients when