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Sample records for circulating vascular progenitors

  1. Circulating Endothelial Progenitor Cells and the Risk of Vascular Events after Ischemic Stroke

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    Martí-Fàbregas, Joan; Delgado-Mederos, Raquel; Crespo, Javier; Peña, Esther; Marín, Rebeca; Jiménez-Xarrié, Elena; Fernández-Arcos, Ana; Pérez-Pérez, Jesús; Martínez-Domeño, Alejandro; Camps-Renom, Pol; Prats-Sánchez, Luís; Casoni, Francesca; Badimon, Lina

    2015-01-01

    Background and Purpose We evaluated the hypothesis that the number of circulating EPC could be associated with the risk of stroke recurrence (SR) or vascular events (VE) after an ischemic stroke. Methods We studied prospectively consecutive patients with cerebral infarction within the first 48 hours after the onset. We recorded demographic factors, vascular risk factors, previous Rankin scale (RS) score, and etiology. We analyzed EPC counts by flow cytometry in blood collected at day 7 and defined EPC as CD34+/CD133+/KDR+ cells. Mean follow-up was 29.3 ± 16 months. We evaluated SR as well as VE. Patients were classified as to the presence or absence of EPC in the circulation (either EPC+ or EPC-). Bivariate analyses, Kaplan-Meier survival curves and Cox regression models were used. Results We included 121 patients (mean age 70.1±12.6 years; 65% were men). The percentage of EPC+ patients was 47.1%. SR occurred in 12 (9.9%) and VE in 18 (14.9%) patients. SR was associated significantly with a worse prior RS score, previous stroke and etiology, but not with EPC count. VE were associated significantly with EPC-, worse prior RS score, previous stroke, high age, peripheral artery disease and etiology. Cox regression model showed that EPC- (HR 7.07, p=0.003), age (HR 1.08, p=0.004) and a worse prior RS score (HR 5.8, p=0.004) were associated significantly with an increased risk of VE. Conclusions The absence of circulating EPC is not associated with the risk of stroke recurrence, but is associated with an increased risk of future vascular events. PMID:25874380

  2. Mobilization of Circulating Vascular Progenitors in Cancer Patients Receiving External Beam Radiation in Response to Tissue Injury

    International Nuclear Information System (INIS)

    Purpose: Endothelial-like vascular progenitor cells (VPCs) are associated with the repair of ischemic tissue injury in several clinical settings. Because the endothelium is a principal target of radiation injury, VPCs may be important in limiting toxicity associated with radiotherapy (RT) in patients with cancer. Methods and Materials: We studied 30 patients undergoing RT for skin cancer (n = 5), head-and-neck cancer (n = 15), and prostate cancer (n = 10) prospectively, representing a wide range of irradiated mucosal volumes. Vascular progenitor cell levels were enumerated from peripheral blood at baseline, midway through RT, at the end of treatment, and 4 weeks after radiation. Acute toxicity was graded at each time point by use of the National Cancer Institute's Common Toxicity Criteria, version 3.0. Results: Significant increases in the proportion of CD34+/CD133+ VPCs were observed after completion of RT, from 0.012% at baseline to 0.048% (p = 0.029), and the increase in this subpopulation was most marked in patients with Grade 2 peak toxicity or greater after RT (p = 0.034). Similarly, CD34+/vascular endothelial growth factor receptor 2-positive VPCs were increased after the completion of radiation therapy in comparison to baseline (from 0.014% to 0.027%, p = 0.043), and there was a trend toward greater mobilization in patients with more significant toxicity (p = 0.08). The mobilization of CD34+ hematopoietic stem cells did not increase after treatment (p = 0.58), and there was no relationship with toxicity. Conclusions: We suggest that VPCs may play an important role in reducing radiation-induced tissue damage. Interventions that increase baseline VPC levels or enhance their mobilization and recruitment in response to RT may prove useful in facilitating more rapid and complete tissue healing.

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

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

    2016-01-01

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

  4. Impairment of circulating endothelial progenitors in Down syndrome

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    Costa Valerio

    2010-09-01

    Full Text Available Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered

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

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    Duong, Heng; Erzurum, Serpil; Asosingh, Kewal

    2011-01-01

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

  6. Accelerating Vascularization in Polycaprolactone Scaffolds by Endothelial Progenitor Cells

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    Singh, Shivani; Wu, Benjamin M.; Dunn, James C.Y.

    2011-01-01

    Vascularization is a major challenge in tissue engineering. The purpose of this study is to expedite the formation of blood vessels in porous polycaprolactone (PCL) scaffolds by the delivery of endothelial progenitor cells (EPCs). To establish a pro-angiogenic and pro-vasculogenic microenvironment, we employed EPCs seeded in PCL scaffold with surface-immobilized heparin and vascular endothelial growth factor (VEGF). EPCs seeded on scaffolds with VEGF exhibited phosphorylation of the receptor....

  7. Vascular progenitor cells in arterial remodeling

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    Grudzinska, Monika K.

    2011-01-01

    Cardiovascular disease is the leading cause of global mortality and physical disability mainly due to the complications such as myocardial infarction or stroke. Physiological healing reaction takes place in the diseased vessel wall aimed to repair the vessel after an injury. There are two factors essentially important for clinical improvement of vascular diseases. The first one is protection of the vascular damage, and the second one is repair of injured, ischemic and regenerating tissues to ...

  8. 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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  10. 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

  11. Decreased circulating endothelial progenitor cell levels and function in patients with nonalcoholic fatty liver disease.

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    Chia-Hung Chiang

    Full Text Available OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs, and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD might have decreased endothelial progenitor cell (EPC levels and attenuated EPC function. METHODS AND RESULTS: A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+, CD34(+KDR(+, and CD34(+KDR(+CD133(+ in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05, attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34(+KDR(+ [cells/10(5 events] was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69-0.89, P<0.001. CONCLUSIONS: NAFLD patients have decreased circulating EPC numbers and

  12. Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy.

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    Georgescu, Adriana

    2011-06-15

    The vascular endothelium is a critical determinant of diabetes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The mechanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The present review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine. PMID:21860692

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

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

    2012-06-01

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

  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. Stromal vascular progenitors in adult human adipose tissue

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    Zimmerlin, Ludovic; Donnenberg, Vera S.; Pfeifer, Melanie E.; Meyer, E. Michael; Péault, Bruno; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    Background The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Methods Immunohistostaining of intact adipose tissue was used to identify 3 markers (CD31, CD34, CD146) which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90, CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture and tested for adipogenesis. Results The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/α-SMA+/CD90±/CD34−/CD31−; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146−/α-SMA−/CD90+/CD34+/CD31−. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), while small vessel endothelium was CD31+/CD34−/CD90− (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31− pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared to unsorted expanded SVF cells. Conclusions In adipose tissue perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34− pericytes, and the outermost of CD146−/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD

  16. Heavy and moderate interval exercise training alters low-flow-mediated constriction but does not increase circulating progenitor cells in healthy humans

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    Rakobowchuk, M; E. Harris; Taylor, A.; Baliga, V; Cubbon, RM; Rossiter, HB; Birch, KM

    2011-01-01

    Moderate-intensity endurance exercise training improves vascular endothelial vasomotor function; however, the impact of high-intensity exercise training has been equivocal. Thus, the effect of the physiological stress of the exercise remains poorly understood. Furthermore, enhanced vascular repair mediated by circulating progenitor cells may also be improved. To address whether the physiological stress of exercise training is an important factor contributing to these adaptations, 20 healthy p...

  17. Endothelial progenitor cell recruitment in a microfluidic vascular model.

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    Lewis, Daniel M; Abaci, Hasan E; Xu, Yu; Gerecht, Sharon

    2015-12-01

    During vessel injury, endothelial progenitors cells (EPCs) are recruited from bone marrow and directed to the hypoxic injury site. The hypoxic conditions in the damaged blood vessel promote TNF-α, which upregulates intercellular adhesion molecule-1 (ICAM-1). EPCs attach to endothelial cell lining using ICAM-1. Here we aimed to examine EPC attachment to ECs in an injured-blood vessel conditions. We first determined ICAM-1 expression in stimulated HUVECs. We stimulated HUVECs with 21% oxygen (atmospheric), atmospheric with TNF-α-supplemented media, 1% oxygen (hypoxia), and hypoxia with TNF-α-supplemented media and found the highest ECFC attachment on HUVECs stimulated with TNF-α and hypoxia, correlating with the highest ICAM-1 expression. We next designed, fabricated and tested a three-dimensional microbioreactor (3D MBR) system with precise control and monitoring of dissolve oxygen and media flow rate in the cellular environment. We utilized a step-wise seeding approach, producing monolayer of HUVECs on all four walls. When stimulated with both TNF-α and hypoxia, ECFC retention on HUVECs was significantly increased under low shear stress compared to static controls. Overall, the 3D MBR system mimics the pathological oxygen tension and shear stress in the damaged vasculature, providing a platform to model vascular-related disorders. PMID:26693599

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

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiu-hua; SHE Ming-peng

    2007-01-01

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

  19. Circulating endothelial progenitor cells in kidney transplant patients.

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    Giovana S Di Marco

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

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

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

    2016-06-01

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

  1. 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

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

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    Alexandra Maria Giovanna Brunasso

    2016-04-01

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

  3. Effect of inflammation induced by prolonged exercise on circulating erythroid progenitors and markers of erythropoiesis

    OpenAIRE

    Premetis, Evangelos; Skenderi, Katerina; Graphakos, Stelios; Baltopoulos, Panayiotis; Tsironi, Maria; Papassotiriou, Ioannis

    2009-01-01

    Background: Exercise in humans augments the mobilization of circulating hematopoietic progenitor cells (CD34+) from the bone marrow. We investigated the effect of inflammation on erythroid marrow activity by mobilization of erythroid progenitor cells (EPs) along with soluble markers of erythropoiesis. Methods: Ten healthy athletes who participated in an ultradistance foot race participated in the study. Peripheral blood mononuclear cells were isolated, before (phase I), at the end (phase II)...

  4. Levels and values of circulating endothelial progenitor cells, soluble angiogenic factors, and mononuclear cell apoptosis in liver cirrhosis patients

    Directory of Open Access Journals (Sweden)

    Chen Chih-Hung

    2012-07-01

    Full Text Available Abstract Background The roles of circulating endothelial progenitor cell (EPC and mononuclear cell apoptosis (MCA in liver cirrhosis (LC patients are unknown. Moreover, vascular endothelial growth factor (VEGF and stromal cell-derived factor (SDF-1α are powerful endogenous substances enhancing EPC migration into circulation. We assessed the level and function of EPCs [CD31/CD34 (E1, KDR/CD34 (E2, CXCR4/CD34 (E3], levels of MCA, VEGF and SDF-1α in circulation of LC patients. Methods Blood sample was prospectively collected once for assessing EPC level and function, MCA, and plasma levels of VEGF and SDF-1α using flow cytometry and enzyme-linked immunosorbent assay (ELISA, respectively, in 78 LC patients and 25 age- and gender-matched healthy controls. Results Number of EPCs (E1, E2, E3 was lower (all p 2, E3 was higher but MCA was lower (all p  Conclusion The results of this study demonstrated that level, angiogenic capacity, and function of circulating EPCs were significantly reduced, whereas plasma levels of SDF-1α and circulating MCA were substantially enhanced in cirrhotic patients.

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

    Directory of Open Access Journals (Sweden)

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2008-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  12. Vascular smooth muscle cell differentiation from human stem/progenitor cells.

    Science.gov (United States)

    Steinbach, Sarah K; Husain, Mansoor

    2016-05-15

    Transplantation of vascular smooth muscle cells (VSMCs) is a promising cellular therapy to promote angiogenesis and wound healing. However, VSMCs are derived from diverse embryonic sources which may influence their role in the development of vascular disease and in its therapeutic modulation. Despite progress in understanding the mechanisms of VSMC differentiation, there remains a shortage of robust methods for generating lineage-specific VSMCs from pluripotent and adult stem/progenitor cells in serum-free conditions. Here we describe a method for differentiating pluripotent stem cells, such as embryonic and induced pluripotent stem cells, as well as skin-derived precursors, into lateral plate-derived VSMCs including 'coronary-like' VSMCs and neural crest-derived VSMC, respectively. We believe this approach will have broad applications in modeling origin-specific disease vulnerability and in developing personalized cell-based vascular grafts for regenerative medicine. PMID:26678794

  13. Spartathlon, a 246 kilometer foot race: effects of acute inflammation induced by prolonged exercise on circulating progenitor reparative cells.

    Science.gov (United States)

    Goussetis, Evgenios; Spiropoulos, Antonia; Tsironi, Maria; Skenderi, Katerina; Margeli, Alexandra; Graphakos, Stelios; Baltopoulos, Panayiotis; Papassotiriou, Ioannis

    2009-01-01

    Endothelial progenitor cells (EPCs) and the recently described circulating fibrocytes (CFs) are strongly associated with tissue repair. We investigated the kinetics of both "repair" progenitor cells in healthy athletes who participated in the "Spartahlon" ultradistance foot race (246 km continuous running exercise), which provides a unique model of inducing dramatic systemic inflammatory changes. Peripheral blood mononuclear cells (PBMCs) were isolated from 10 volunteer athletes, who completed successfully the race, before, at the end, and at 48 h post-race. EPCs and CFs were detected as endothelial colony-forming units (CFU-ECs) and as the number of adherent with a spindle-shaped morphology Collagen I(+) cells detected after 6-day culture of PBMCs, respectively. The marked increase of plasma levels of CRP, IL-6, SAA, MCP-1, IL-8, sVCAM-1, sICAM-1, thrombomodulin (sTM) and NT-pro-BNP at the end of race established acute inflammation and tissue injury. EPCs increased by nearly eleven-fold in peripheral blood at the end of the race from 44.5+/-2.5/ml to 494.6+/-27.9/ml and remained increased 428.5+/-31.5/ml at 48 h post-race (p<0.0001). The number of the fibrocytes cultured from PBMCs obtained before, at the end, and 48 h post-race did not reveal any significant difference. These findings indicate that bone marrow responses to acute inflammatory damage, induced by exhausting exercise, with a rapid release of EPCs but not CFs into circulation. Given the ability of EPCs to promote angiogenesis and vascular regeneration, we may suggest that this kind of cell mobilization may serve as a physiologic repair mechanism in acute inflammatory tissue injury. PMID:19233694

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

    Science.gov (United States)

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

    2016-06-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Julia M Kröpfl

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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

    OpenAIRE

    Corral, Luisa; Javierre, Casimiro; Blasi, Juan; Viscor, Ginés; Ricart, Antoni; Ventura, Josep Lluis

    2014-01-01

    Background Our goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC) and increase their concentration in peripheral circulation. Methods Nine healthy male subjects were subjected, as the active group (HME), to a protocol involving IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric pressure of 540 hP...

  19. Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.

    Science.gov (United States)

    Stelzer, I; Kröpfl, J M; Fuchs, R; Pekovits, K; Mangge, H; Raggam, R B; Gruber, H-J; Prüller, F; Hofmann, P; Truschnig-Wilders, M; Obermayer-Pietsch, B; Haushofer, A C; Kessler, H H; Mächler, P

    2015-10-01

    Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration. PMID:25438993

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

    OpenAIRE

    Paradis, Alexandra; Zhang, Lubo

    2013-01-01

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

  1. 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.

  2. SCL/Tal-1 transcription factor acts downstream of cloche to specify hematopoietic and vascular progenitors in zebrafish

    OpenAIRE

    Liao, Eric C.; Paw, Barry H.; Oates, Andrew C; Pratt, Stephen J.; Postlethwait, John H.; Zon, Leonard I.

    1998-01-01

    SCL/Tal-1 is a transcription factor necessary for hematopoietic stem cell differentiation. Although SCL is also expressed in endothelial and neural progenitors, SCL function in these cells remains unknown. In the zebrafish mutant cloche (clo), SCL expression is nearly abolished in hematopoietic and vascular tissues. Correspondingly, it was shown previously that clo fails to differentiate blood and angioblasts. Genetic analysis demonstrates that the clo mutation is not linked to the SCL locus....

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

    Science.gov (United States)

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

    2016-08-01

    Novel strategies for a tailored risk prediction in chronic heart failure (CHF) are crucial to identify patients at very high risk for an improved patient management and to specify treatment regimens. Endothelial progenitor cells (EPCs) are an important endogenous repair mechanism with the ability to counteract endothelial injury and the possibility of new vessel formation. We hypothesised that exhaustion of circulating EPCs may be a suitable prognostic biomarker in patients with CHF. EPCs, defined as CD34+CD45dimKDR+ cells, were analysed using fluorescence-activated cell sorting. EPCs were measured in 185 patients with CHF including 87 (47 %) patients with ischaemic aetiology and 98 (53 %) patients with non-ischaemic CHF and followed for a median time of 2.7 years. During this period, 34.7 % of patients experienced the primary study endpoint all-cause mortality. EPC count was a significant and independent inverse predictor of mortality with an hazard ratio hazard ratio (HR) per increase of one standard deviation (1-SD) of 0.47 (95 % confidence interval [CI]: 0.35-0.61; pHR per 1-SD of 0.54 (95 % CI: 0.4-0.73; p<0.001). EPCs further demonstrated additional prognostic information indicated by improvements in C-statistic, net reclassification index and integrated discrimination increment. In conclusion, in our study circulating EPCs turned out as strong and independent inverse predictors of mortality underlining the importance of an impaired endothelial repair mechanism in the pathophysiology and progression of CHF. PMID:27412580

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

    Directory of Open Access Journals (Sweden)

    Nicoleta Alexandru

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

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

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

    OpenAIRE

    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 possibilit...

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

    OpenAIRE

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

    2011-01-01

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

  11. Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications

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    Poojitha Rajasekar

    2015-01-01

    Full Text Available The vascular complications of diabetes significantly impact the quality of life and mortality in diabetic patients. Extensive evidence from various human clinical trials has clearly established that a period of poor glycemic control early in the disease process carries negative consequences, such as an increase in the development and progression of vascular complications that becomes evident many years later. Importantly, intensive glycemic control established later in the disease process cannot reverse or slow down the onset or progression of diabetic vasculopathy. This has been named the glycemic memory phenomenon. Scientists have successfully modelled glycemic memory using various in vitro and in vivo systems. This review emphasizes that oxidative stress and accumulation of advanced glycation end products are key factors driving glycemic memory in endothelial cells. Furthermore, various epigenetic marks have been proposed to closely associate with vascular glycemic memory. In addition, we comment on the importance of endothelial progenitors and their role as endogenous vasoreparative cells that are negatively impacted by the diabetic milieu and may constitute a “carrier” of glycemic memory. Considering the potential of endothelial progenitor-based cytotherapies, future studies on their glycemic memory are warranted to develop epigenetics-based therapeutics targeting diabetic vascular complications.

  12. Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

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    Saggese Giuseppe

    2011-10-01

    Full Text Available Abstract Background Carotid intima-media thickness (IMT, indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM. The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs, glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs, soluble receptors for AGEs (sRAGE and adiponectin were evaluated. Methods Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1% and 26 controls (mean age 19 ± 2 years were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70 was used to measure carotid IMT and wave speed (WS, index of local stiffness, applanation tonometry (PulsePen was applied to obtain central pulse pressure (PP and augmentation index (AIx, and carotid-femoral pulse wave velocity (PWV, Complior was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT. Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method, sRAGE and adiponectin were also measured. Results After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p Conclusions Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2006-01-01

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

  15. Circulating endothelial progenitor cells in castration resistant prostate cancer: a randomized, controlled, biomarker study.

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    Thorsten Fuereder

    Full Text Available BACKGROUND: Endothelial progenitor cells (CEPs and circulating endothelial cells (CECs are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC patients. PATIENTS AND METHODS: Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d, in combination with docetaxel (75 mg/m2 or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy. RESULTS: A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001. However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30% patients responded to therapy with a 50% PSA decline, while 9 (64% patients showed a PSA decline in the combination group (n.s.. The median PFS in the docetaxel monotherapy group was 3.1 months (2.6-3.6 months, 95% CI and 6.2 months (4.9-7.4 months, 95% CI; p = 0.062 in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable. CONCLUSION: In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However

  16. 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

  17. Angiogenic potential modulation of human endothelial progenitor cells by vascular plasmatic biomarkers

    OpenAIRE

    d'Audigier, Clément,

    2013-01-01

    Rationale: The pro-angiogenic capacities of endothelial progenitor cells are now well established, and their involvement in neovascularization events in adults has stimulated the research in the field of angiogenic therapy based on transplant of these cells. Current data converge towards the notion of two cell types with endothelial phenotype, defined at least by their kinetics of appearance in culture: early endothelial progenitor cells (CFU-EC or CAC) and late (ECFC). Our team has shown tha...

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

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    Maria Tikhonenko

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

  19. Bioengineered fibrin-based niche to direct outgrowth of circulating progenitors into neuron-like cells for potential use in cellular therapy

    Science.gov (United States)

    Tara, S.; Krishnan, Lissy K.

    2015-06-01

    Objective. Autologous cells are considered to be the best choice for use in transplantation therapy. However, the challenges and risks associated with the harvest of transplantable autologous cells limit their successful therapeutic application. The current study explores the possibility of isolating neural progenitor cells from circulating multipotent adult progenitor cells for potential use in cell-based and patient-specific therapy for neurological diseases. Approach. To enable the selection of neural progenitor cells from human peripheral blood mononuclear cells, and to support their lineage maintenance, the composition of a fibrin-based niche was optimized. Morphological examination and specific marker analysis were carried out, employing a qualitative/quantitative polymerase chain reaction followed by immunocytochemistry to: (i) characterize neural progenitor cells in culture; (ii) monitor proliferation/survival; and (iii) track their differentiation status. Main results. The presence of neural progenitors in circulation was confirmed by the presence of nestin+ cells at the commencement of the culture. The isolation, proliferation and differentiation of circulating neural progenitors to neuron-like cells were directed by the engineered niche. Neural cell isolation to near homogeneity was confirmed by the expression of β-III tubulin in ∼95% of cells, whereas microtubule associated protein-2 expression confirmed their ability to differentiate. The concentration of potassium chloride in the niche was found to favour neuron-like cell lengthening, cell-cell contact, and expressions of synaptophysin and tyrosine hydroxylase. Significance. The purpose of this research was to find out if peripheral blood could serve as a potential source of neural progenitors for cell based therapy. The study established that neural progenitors could be selectively isolated from peripheral blood mononuclear cells using a biomimetic niche. The selected cells could multiply and

  20. 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.

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

    Science.gov (United States)

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

    2016-08-01

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

  2. 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; Nielsen, Hans Jørgen

    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 undergon...

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

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    Jeanine M. Roodhart

    2010-01-01

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

  4. Dysregulation of ossification-related miRNAs in circulating osteogenic progenitor cells obtained from patients with aortic stenosis.

    Science.gov (United States)

    Takahashi, Kan; Satoh, Mamoru; Takahashi, Yuji; Osaki, Takuya; Nasu, Takahito; Tamada, Makiko; Okabayashi, Hitoshi; Nakamura, Motoyuki; Morino, Yoshihiro

    2016-07-01

    CAVD (calcific aortic valve disease) is the defining feature of AS (aortic stenosis). The present study aimed to determine whether expression of ossification-related miRNAs is related to differentiation intro COPCs (circulating osteogenic progenitor cells) in patients with CAVD. The present study included 46 patients with AS and 46 controls. Twenty-nine patients underwent surgical AVR (aortic valve replacement) and 17 underwent TAVI (transcatheter aortic valve implantation). The number of COPCs was higher in the AS group than in the controls (Pperipheral blood mononuclear cells transfected with each ossification-related miRNA showed that these miRNAs controlled levels of osteocalcin protein. In conclusion, dysregulation of ossification-related miRNAs may be related to the differentiation into COPCs and may play a significant role in the pathogenesis of CAVD. PMID:27129184

  5. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Abdominal vascular responses to changes in carbon dioxide tension in the cephalic circulation of anaesthetized dogs.

    Science.gov (United States)

    Ford, R; Hainsworth, R; Rankin, A J; Soladoye, A O

    1985-01-01

    Dogs were anaesthetized with chloralose, the regions of both carotid sinuses were vascularly isolated and perfused with arterial blood and both cervical vagosympathetic trunks were cut above the nodose ganglia. The cephalic circulation was perfused through the brachiocephalic and left subclavian arteries with blood which was equilibrated with various levels of CO2. The abdomen was vascularly isolated, perfused through the aorta at constant flow and drained through the inferior vena cava at constant pressure. Changes in vascular resistance were determined from changes in abdominal aortic perfusion pressure and changes in capacitance from the integral of the changes in venous outflow. An increase in PCO2 in the cephalic perfusate resulted in an increase in abdominal vascular resistance and a decrease in capacitance. However, when carotid sinus pressure was high, the response of resistance to an increase in cephalic PCO2 was abolished and that of capacitance was significantly reduced. The reflex responses of both vascular resistance and capacitance to a change in carotid sinus pressure were enhanced when the cephalic PCO2 was raised. However, the effect on the reflex capacitance response from stimulation of baroreceptors was obtained only when PCO2 was changed below 5 kPa whereas the effect on resistance occurred at higher values of PCO2. The interaction between the effects of changes in cephalic PCO2 and the carotid sinus reflex and the differential effect on resistance and capacitance vessels have been explained in terms of the known difference in the sensitivities of these vessels to sympathetic nerve activity. PMID:3920388

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

    Science.gov (United States)

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

    2016-05-01

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

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

    International Nuclear Information System (INIS)

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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

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

  15. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    The effects of ionizing radiation (IR) on tumor neovascularization are still unclear. We previously reported that vascular endothelial cells (ECs) expressing the IR-induced senescence-like (IRSL) phenotype exhibit a significant decrease in angiogenic activity in vitro. In this study, we examined the effects of the IRSL phenotype on adhesion to early endothelial progenitor cells (early EPCs). Adhesion of human peripheral blood-derived early EPCs to human umbilical vein endothelial cells (HUVECs) expressing the IRSL phenotype was evaluated by an adhesion assay under static conditions. It was revealed that the IRSL HUVECs supported significantly more adhesion of early EPCs than normal HUVECs. Expressions of ICAM-1, VCAM-1 and E-selectin were up-regulated in IRSL HUVECs. Pre-treatment of IRSL HUVECs with adhesion-blocking monoclonal antibodies against E-selectin and VCAM-1 significantly reduced early EPC adhesion to IRSL HUVECs, suggesting a potential role for the E-selectin and VCAM-1 in the adhesion between IRSL ECs and early EPCs. Therefore, the IRSL phenotype expressed in ECs may enhance neovascularization via increased homing of early EPCs. Our findings are first to implicate the complex effects of this phenotype on tumor neovascularization following irradiation. (author)

  16. 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.

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

    Science.gov (United States)

    Maciorkowska, Dominika; Zbroch, Edyta; Malyszko, Jolanta

    2015-11-01

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

  18. Circulating progenitor cells during exercise, muscle electro-stimulation and intermittent hypobaric hypoxia in patients with traumatic brain injury. A pilot study

    OpenAIRE

    Corral Ansa, Luisa; Conde, L; Guillamó Casanoves, Elisabet; Blasi Cabús, Joan; Juncadella i Puig, Montserrat; Javierre Garcés, Casimiro F.; Viscor Carrasco, Ginés; Ventura i Farré, Josep Lluís

    2014-01-01

    BACKGROUND: Circulating progenitor cells (CPC) treatments may have great potential for the recovery of neurons and brain function. OBJECTIVE: To increase and maintain CPC with a program of exercise, muscle electro-stimulation (ME) and/or intermittent-hypobaric-hypoxia (IHH), and also to study the possible improvement in physical or psychological functioning of participants with Traumatic Brain Injury (TBI). METHODS: Twenty-one participants. Four groups: exercise and ME group (EEG), cycling gr...

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

    Directory of Open Access Journals (Sweden)

    Khazaei Majid

    2011-02-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Iván eRodríguez

    2014-09-01

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

  2. Mobilization of stem and progenitor cells in cardiovascular diseases

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tatjana M H Niers

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

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

    Directory of Open Access Journals (Sweden)

    Azza Tawfeek Moawed, Nihad Ahmed El Nashar

    2012-04-01

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

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

    OpenAIRE

    Mariani Santosa; Ermita I.I. Ilyas; Radiana D. Antarianto

    2016-01-01

    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 ...

  7. Study on correlation between circulating endothelial progenitor cells and brain natriuretic peptide in patients with myocardial infarction complicated heart failure after stem cell mobilization

    Directory of Open Access Journals (Sweden)

    Zi-lin ZHAO

    2014-06-01

    Full Text Available Objective: It is to observe the correlation between circulating endothelial progenitor cells (endothelial progenitor cells, EPCs and brain natriuretic peptide (BNP in patients with myocardial infarction and heart failure after stem cell mobilizer granulocyte colony stimulating factor (granulocyte colony stimulating factor, G-CSF.Methods: Patients were divided into the control group(37 and the observation group (38. The observation group took injection of G-CSF, 10μg/kg, for 7d. The Two groups were observed the amount of circulating EPCs , the levels of BNP, TNF- α and other indicators, and make clinical analysis. Results: Compared with control group, the amount of EPCs were significantly increased, the level of BNP, TNF- α were decreased, the difference between the observation group and control group is statistical significant (P < 0.05; the amount of  EPCs had negative correlation with BNP. Conclusion: The application of stem cell mobilization of circulating EPCs can improve the clinical curative effect of myocardial infarction patients and heart failure, cyclic EPCs and BNP detection can effectively evaluate the heart function and prognosis.

  8. 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.

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  11. In vivo endothelization of tubular vascular grafts through in situ recruitment of endothelial and endothelial progenitor cells by RGD-fused mussel adhesive proteins

    International Nuclear Information System (INIS)

    The use of tissue mimics in vivo, including patterned vascular networks, is expected to facilitate the regeneration of functional tissues and organs with large volumes. Maintaining patency of channels in contact with blood is an important issue in the development of a functional vascular network. Endothelium is the only known completely non-thrombogenic material; however, results from treatments to induce endothelialization are inconclusive. The present study was designed to evaluate the clinical applicability of in situ recruitment of endothelial cells/endothelial progenitor cells (EC/EPC) and pre-endothelization using a recombinant mussel adhesive protein fused with arginine–glycine–aspartic acid peptide (MAP-RGD) coating in a model of vascular graft implantation. Microporous polycaprolactone (PCL) scaffolds were fabricated with salt leaching methods and their surfaces were modified with collagen and MAP-RGD. We then evaluated their anti-thrombogenicity with an in vitro hemocompatibility assessment and a 4-week implantation in the rabbit carotid artery. We observed that MAP-RGD coating reduced the possibility of early in vivo graft failure and enhanced re-endothelization by in situ recruitment of EC/EPC (patency rate: 2/3), while endothelization prior to implantation aggravated the formation of thrombosis and/or IH (patency rate: 0/3). The results demonstrated that in situ recruitment of EC/EPC by MAP-RGD could be a promising strategy for vascular applications. In addition, it rules out several issues associated with pre-endothelization, such as cell source, purity, functional modulation and contamination. Further evaluation of long term performance and angiogenesis from the luminal surface may lead to the clinical use of MAP-RGD for tubular vascular grafts and regeneration of large-volume tissues with functional vascular networks. (paper)

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

    OpenAIRE

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

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  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

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

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

    OpenAIRE

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

    2013-01-01

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

  16. Chronic Treatment with Clenbuterol Modulates Endothelial Progenitor Cells and Circulating Factors in a Murine Model of Cardiomyopathy

    OpenAIRE

    Rider, James E.; Polster, Sean P.; Lee, Sangjin; Charles, Nathan J.; Adhikari, Neeta; Mariash, Ami; Tadros, George; Stangland, Jenna; Smolenski, Ryszard T.; Terracciano, Cesare M.; Barton, Paul J R.; Birks, Emma J.; Yacoub, Magdi H; Miller, Leslie W.; Hall, Jennifer L.

    2009-01-01

    The purpose of this study was to determine the effects of chronic treatment with the beta 2 adrenergic receptor agonist clenbuterol on endothelial progenitor cells (EPC) in a well-characterized model of heart failure, the muscle LIM protein knockout (MLP−/−) mouse. MLP−/−mice were treated daily with clenbuterol (2 mg/kg) or saline subcutaneously for 6 weeks. Clenbuterol led to a 30% increase in CD31+ cells in the bone marrow of MLP−/− heart failure mice (p

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

    Science.gov (United States)

    Hennig, E

    1992-01-01

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

  18. 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

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

    OpenAIRE

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

    2010-01-01

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

  20. A novel oxygen carrier “YQ23” suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells

    International Nuclear Information System (INIS)

    Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury. An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs). Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment. YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs

  1. 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.

    2016-01-01

    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. PMID:27145015

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

    Science.gov (United States)

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

    2015-04-01

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

  3. High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects.

    Science.gov (United States)

    Sesti, G; Andreozzi, F; Fiorentino, T V; Mannino, G C; Sciacqua, A; Marini, M A; Perticone, F

    2014-10-01

    Irisin, a novel myokine, was proposed to be able to regulate glucose homeostasis and obesity in mice. Whether irisin levels are associated with cardio-metabolic variables, insulin sensitivity, and vascular atherosclerosis in humans remain unsettled. To determine the associations between circulating irisin levels, cardio-metabolic variables, insulin sensitivity, and common carotid intima-media thickness (IMT), an indicator of vascular atherosclerosis, a cross-sectional evaluation of circulating irisin levels and cardio-metabolic variables in 192 White adults was conducted. Insulin sensitivity and insulin clearance were assessed by euglycemic-hyperinsulinemic clamp. Common carotid IMT was measured by ultrasound. After adjusting for age and gender, irisin levels were positively correlated with body fat mass (r = 0.12, P < 0.05), fasting (r = 0.17, P < 0.01), 2 h post-load insulin (r = 0.15, P < 0.02) levels, and IMT (r = 0.29, P < 0.0001) and were negatively correlated with insulin-stimulated glucose disposal (r = -0.18, P = 0.007), Matsuda index (r = -0.13, P < 0.04), disposition index (r = -0.278, P < 0.0001), and insulin clearance (r = -0.26, P < 0.0001). After adjusting for age, gender, and BMI, individuals in the highest tertile of irisin levels exhibited higher body fat mass (P < 0.01), fasting (P < 0.05), 2 h post-load (P < 0.01) insulin levels, carotid IMT (P < 0.001), lower insulin-stimulated glucose disposal (P < 0.001), Matsuda index (P < 0.01), disposition index (P < 0.01), and insulin clearance (P < 0.001) as compared with subjects in the lowest tertile of circulating irisin levels. Irisin is inversely associated with insulin sensitivity and positively associated with carotid IMT in humans, suggesting either increased release by adipose/muscle tissue in response to deterioration of insulin sensitivity or a compensatory increase in irisin to overcome an underlying irisin resistance. PMID:24619655

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

    Directory of Open Access Journals (Sweden)

    Frank Joseph

    2011-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Sadikovic Suwad

    2009-12-01

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

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

  8. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

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

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

    International Nuclear Information System (INIS)

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

  10. 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

  11. Elevated circulating vascular cell Adhesion Molecule-1 (sVCAM-1) is associated with concurrent depressive symptoms and cerebral white matter Hyperintensities in older adults

    OpenAIRE

    Tchalla, Achille E.; Wellenius, Gregory A.; Sorond, Farzaneh A.; Travison, Thomas G.; Dantoine, Thierry; Lipsitz, Lewis A.

    2015-01-01

    Background: Circulating vascular adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial activation and dysfunction, but little is known about its association with mood. We hypothesized that elevated plasma concentrations of sVCAM-1 may be a marker of depressive symptoms due to cerebral vascular disease. Methods: We studied 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. sICAM-1 and sVCAM-1 were measured by ELISA assay and depressive sympto...

  12. 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.

  13. 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

  14. Circulating Angiogenic Factors in Patients with Thromboangiitis Obliterans

    OpenAIRE

    Hewing, Bernd; Stangl, Verena; Stangl, Karl; Enke-Melzer, Kathrin; Baumann, Gert; Ludwig, Antje

    2012-01-01

    Background Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO. Methodology/Principa...

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

    Directory of Open Access Journals (Sweden)

    Dilyana Todorova

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

  16. Lung Circulation.

    Science.gov (United States)

    Suresh, Karthik; Shimoda, Larissa A

    2016-01-01

    The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. © 2016 American Physiological Society. Compr Physiol 6:897-943, 2016. PMID:27065170

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

    OpenAIRE

    2015-01-01

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

  18. 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

    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 ...

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

    OpenAIRE

    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 se...

  20. Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease

    OpenAIRE

    Radom-Aizik, Shlomit; Zaldivar, Frank P.; Haddad, Fadia; Cooper, Dan M.

    2014-01-01

    Physical activity can prevent and/or attenuate atherosclerosis, a disease clearly linked to inflammation. Paradoxically, even brief exercise induces a stress response and increases inflammatory cells like monocytes in the circulation. We hypothesized that exercise would regulate the expression of genes, gene pathways, and microRNAs in monocytes in a way that could limit pro-inflammatory function and drive monocytes to prevent, rather than contribute to, atherosclerosis. Twelve healthy men (22...

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

    Directory of Open Access Journals (Sweden)

    Yvonne eKilian

    2016-03-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult...

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

    Directory of Open Access Journals (Sweden)

    Yoka H. Kusumanto

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  5. 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

    Framingham Offspring cohort. METHODS: We followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and...... 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 are...

  6. Circulating angiogenic factors in patients with thromboangiitis obliterans.

    Directory of Open Access Journals (Sweden)

    Bernd Hewing

    Full Text Available BACKGROUND: Thromboangiitis obliterans (TAO, also known as Buerger's disease is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO. METHODOLOGY/PRINCIPAL FINDINGS: TAO patients with critical limb ischemia and age- and gender-matched nonsmokers and smokers without cardiovascular disease (n = 12 in each group were enrolled in the study. Flow cytometric analysis of peripheral blood showed significantly decreased levels of circulating CD45(dimCD34(+ progenitor cells in TAO patients and in smokers compared to nonsmokers. In contrast to both control groups, the proportion of CD45(dimCD34(+ progenitor cells co-expressing VEGF receptor-2 (VEGFR2 was significantly elevated in TAO patients. Enzyme-linked immunosorbent assay (ELISA of common angiogenic factors (such as VEGF did not clearly point to pro- or antiangiogenic conditions in serum or plasma of TAO patients. Serum of TAO patients and controls was evaluated in proliferation, migration (scratch assay and spheroid sprouting assays using human umbilical vein endothelial cells (HUVECs. Serum of TAO patients exhibited a diminished sprouting capacity of HUVECs compared to both control groups. Proliferation and migration of endothelial cells were impaired after treatment with serum of TAO patients. CONCLUSION: Levels of circulating progenitor cells were altered in TAO patients compared to healthy nonsmokers and smokers. Furthermore, serum of TAO patients exhibited an antiangiogenic activity (impaired endothelial cell sprouting, migration and proliferation on endothelial cells, which may contribute to vascular pathology in this patient population.

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

    Directory of Open Access Journals (Sweden)

    Couchman John R

    2008-01-01

    Full Text Available Abstract Background Mouse embryonic stem cells cultured in vitro have the ability to differentiate into cells of the three germ layers as well as germ cells. The differentiation mimics early developmental events, including vasculogenesis and early angiogenesis and several differentiation systems are being used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult. Results CCE mouse embryonic stem cells were differentiated on collagen type IV for 4–5 days, Flk1+ mesodermal cells were sorted and replated either on collagen type IV in the presence of VEGFA to give rise to endothelial cells and smooth muscle cells or in collagen type I gels for the formation of vascular tubes. The activity of the CMV and β-actin promoters was downregulated during selection of stable transfectants and during differentiation to the Flk1 stage, while the CMV immediate enhancer/β-actin promoter in the pCAGIPuro-GFP vector led to 100% of stably transfected undifferentiated and differentiated cells expressing GFP. To further test this system we expressed syndecan-2 and -4 in these cells and demonstrated high levels of transgene expression in both undifferentiated cells and cells differentiated to the Flk1 stage. Conclusion Vectors containing the CAG promoter offer a valuable tool for the long term expression of transgenes during stem cell differentiation towards mesoderm, while the CMV and β-actin promoters lead to very poor transgene expression during this process.

  8. 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

  9. Progenitor Cells and Podocyte Regeneration

    Science.gov (United States)

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

    2014-01-01

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

  10. Endothelial progenitor cells in acute ischemic stroke

    Science.gov (United States)

    Martí-Fàbregas, Joan; Crespo, Javier; Delgado-Mederos, Raquel; Martínez-Ramírez, Sergi; Peña, Esther; Marín, Rebeca; Dinia, Lavinia; Jiménez-Xarrié, Elena; Fernández-Arcos, Ana; Pérez-Pérez, Jesús; Querol, Luis; Suárez-Calvet, Marc; Badimon, Lina

    2013-01-01

    Objectives The levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points. Material and methods We studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0–2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry. Results We included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes. Conclusions After acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months. PMID:24363968

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

    Directory of Open Access Journals (Sweden)

    Jia-Yin Sun

    2013-05-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘微

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. 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.

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

    Science.gov (United States)

    Gebesh, V V; Iarosh, O A

    1991-01-01

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

  19. Vascular Cures

    Science.gov (United States)

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

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

    Institute of Scientific and Technical Information of China (English)

    余东彪; 吴继雄

    2012-01-01

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

  2. 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.

  3. Repetitive hypoglycemia increases circulating adrenaline level with resultant worsening of intimal thickening after vascular injury in male Goto-Kakizaki rat carotid artery.

    Science.gov (United States)

    Yasunari, Eisuke; Mita, Tomoya; Osonoi, Yusuke; Azuma, Kosuke; Goto, Hiromasa; Ohmura, Chie; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

    2014-06-01

    Hypoglycemia associated with diabetes management is a potential risk for cardiovascular diseases. However, the effect of hypoglycemic episodes including a surge of sympathetic activity on the progression of neointima formation after vascular injury remains largely unknown. In this study, insulin was injected intraperitoneally into nonobese diabetic Goto-Kakizaki (GK) rats, once every 3 days for 4 weeks after balloon injury of carotid artery to induce hypoglycemia. Then, we evaluated balloon injury-induced neointima formation. Insulin treatment enhanced neointima formation and increased the number of proliferating cell nuclear antigen (PCNA)-positive cells in the carotid artery. Injection of glucose with insulin prevented hypoglycemia and abrogated intimal thickening. Also, bunazosin, an α1 adrenergic receptor antagonist, prevented intimal thickening and accumulation of PCNA-positive cells induced by insulin treatment despite the presence of concomitant hypoglycemia and high adrenaline levels. Incubation of cultured smooth muscle cells with adrenaline resulted in a significant increase in their proliferation and G0/G1 to S phase progression, which was associated with activation of extracellular signal-regulated kinase, enhanced expression of cell cycle regulatory molecules such as cyclin D1, and cyclin E, and phosphorylation of retinoblastoma protein. These adrenaline-induced effects were abrogated by bunazosin. Our data indicated that increased adrenaline induced by repetitive hypoglycemia promotes intimal thickening and smooth muscle cell proliferation after endothelial denudation in GK rats. PMID:24684300

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    董勇; 李文志; 辛毅; 孙智

    2013-01-01

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

  6. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

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

  7. Analysis of circulating hem-endothelial marker RNA levels in preterm infants

    Directory of Open Access Journals (Sweden)

    Kuint Jacob

    2009-06-01

    Full Text Available Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30. Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (AC133, Tie-2, Flk-1 (VEGFR2 and Scl/Tal1 in association with characteristics of prematurity and preterm morbidity. Results Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA. We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.

  8. PULMONARY CIRCULATION AT EXERCISE

    OpenAIRE

    R. Naeije; CHESLER, N

    2012-01-01

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

  9. Circulating endothelial cells in cardiovascular disease.

    Science.gov (United States)

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

    2006-10-17

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

  10. The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    Science.gov (United States)

    Liberda, Eric N.

    Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

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

    Institute of Scientific and Technical Information of China (English)

    伍大华; 祝皓

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  13. 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

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

    International Nuclear Information System (INIS)

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

  15. GRB Progenitors and Environment

    OpenAIRE

    Lazzati, Davide

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

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

  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. Fetal Circulation

    Science.gov (United States)

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

  19. 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.

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

    Institute of Scientific and Technical Information of China (English)

    刘哲亮; 吴忠仕; 胡建国; 陈勇; 胡野荣; 李伟

    2008-01-01

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

  1. Sox17 is required for normal pulmonary vascular morphogenesis

    OpenAIRE

    Lange, Alexander W.; Haitchi, Hans Michael; LeCras, Timothy D.; Sridharan, Anusha; Xu, Yan; Wert, Susan E.; James, Jeanne; Udell, Nicholas; Thurner, Philipp J.; Whitsett, Jeffrey A.

    2014-01-01

    The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pul...

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pawan Krishan

    2015-06-01

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

  4. Endothelial Progenitor Cells Dysfunction and Senescence: Contribution to Oxidative Stress

    OpenAIRE

    Imanishi, Toshio; Tsujioka, Hiroto; Akasaka, Takashi

    2008-01-01

    The identification of endothelial progenitor cells (EPCs) has led to a significant paradigm in the field of vascular biology and opened a door to the development of new therapeutic approaches. Based on the current evidence, it appears that EPCs may make both direct contribution to neovascularization and indirectly promote the angiogenic function of local endothelial cells via secretion of angiogenic factors. This concept of arterial wall repair mediated by bone marrow (BM)-derived EPCs provid...

  5. 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.

  6. 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

    2016-01-01

    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. PMID:26952167

  7. 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.

  8. Stem cells and progenitor cells in renal disease.

    Science.gov (United States)

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

    2005-11-01

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

  9. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.

    Science.gov (United States)

    Yoder, Mervin C; Mead, Laura E; Prater, Daniel; Krier, Theresa R; Mroueh, Karim N; Li, Fang; Krasich, Rachel; Temm, Constance J; Prchal, Josef T; Ingram, David A

    2007-03-01

    The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration. PMID:17053059

  10. Identification of Progenitor Cell Survival in Peripheral Blood

    International Nuclear Information System (INIS)

    The myeloid progenitors can not survive properly under the usual conditions of blood banking.The aim of work is to assay the survival of myeloid progenitors during varying periods of blood storage, under the usual condition of blood banking. It is an attempt to detect whether or not ,these circulating myeloid progenitors could be stored under the blood banking condition to be used in clinical transplantation protocols to treat a wide variety of refractory diseases.Individual blood samples from forty healthy adults were examined clinically, laboratory and ultrasonography. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque gradients . Serial dilutions of human placental conditioned medium were made, and tested for optimal activity by In vitro cultured technique.This study estimated that the mean levels of absolute number of myeloid progenitors per c.mm. at zero time was 137.7±68.3 (Range 54-297),at day 3 was 71.0±40.2 (Range 54-297), at day 7 was 94.8±45.7 (Range 30 -232) and at day 14 was 45.5±22.7). There was statistically significant decrease in the number of colonies from zero time to day 14. There was statistically significant decrease in the number of myeloid progenitors from zero time to day 14

  11. Norepinephrine Stimulates Mobilization of Endothelial Progenitor Cells after Limb Ischemia

    OpenAIRE

    Jiang, Qijun; Ding, Shifang; Wu, Jianxiang; Liu, Xing; Wu, Zonggui

    2014-01-01

    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...

  12. Diabetes and Retinal Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    2014-01-01

    Full Text Available Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR. We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

  13. Characterisation of resident multipotent vascular stem cell derived smooth muscle cells in culture

    OpenAIRE

    Kennedy, Eimear

    2015-01-01

    The origin of the vascular Smooth Muscle Cell (SMC) involved with vascular remodelling is very controversial. The theory that SMCs can dedifferentiate is long standing. However, in more recent years this idea has been challenged with the emergence of resident progenitor stem cells in the vascular wall. Here, a population of primary Multipotent Vascular Stem Cells (MVSCs) were isolated using explant culture from the medial layer of rat aortic tissue. MVSCs were characterised for multipotency b...

  14. Vascular MR

    International Nuclear Information System (INIS)

    This project investigates cardiac gated gradient echo pulses sequences for vascular MR imaging. These pulse sequences have been used to acquire and display MR projection angiograms. The authors have applied these methods in two distinct populations of patients for evaluation and comparison with standard angiography. Twenty patients with abdominal aortic aneurysms, and 35 patients with aortoiliac atherosclerotic disease or peripheral vascular disease were investigated using this method and the results are presented

  15. Vascular Dementia

    OpenAIRE

    Maria Alekseyevna Cherdak; O. V. Uspenskaya

    2015-01-01

    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment ...

  16. Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells.

    Science.gov (United States)

    Salvatore, Paola; Casamassimi, Amelia; Sommese, Linda; Fiorito, Carmela; Ciccodicola, Alfredo; Rossiello, Raffaele; Avallone, Bice; Grimaldi, Vincenzo; Costa, Valerio; Rienzo, Monica; Colicchio, Roberta; Williams-Ignarro, Sharon; Pagliarulo, Caterina; Prudente, Maria Evelina; Abbondanza, Ciro; Lamberti, Florentia; Baroni, Adone; Buommino, Elisabetta; Farzati, Bartolomeo; Tufano, Maria Antonietta; Ignarro, Louis Joseph; Napoli, Claudio

    2008-07-01

    The recruitment of circulating endothelial progenitor cells (EPCs) might have a beneficial effect on the clinical course of several diseases. Endothelial damage and detachment of endothelial cells are known to occur in infection, tissue ischemia, and sepsis. These detrimental effects in EPCs are unknown. Here we elucidated whether human EPCs internalize Bartonella henselae constituting a circulating niche of the pathogen. B. henselae invades EPCs as shown by gentamicin protection assays and transmission electron microscopy (TEM). Dil-Ac-LDL/lectin double immunostaining and fluorescence-activated cell sorting (FACS) analysis of EPCs revealed EPC bioactivity after infection with B. henselae. Nitric oxide (NO) and its precursor l-arginine (l-arg) exert a plethora of beneficial effects on vascular function and modulation of immune response. Therefore, we tested also the hypothesis that l-arg (1-30 mM) would affect the infection of B. henselae or tumor necrosis factor (TNF) in EPCs. Our data provide evidence that l-arg counteracts detrimental effects induced by TNF or Bartonella infections via NO (confirmed by DETA-NO and L-NMMA experiments) and by modulation of p38 kinase phosphorylation. Microarray analysis indicated several genes involved in immune response were differentially expressed in Bartonella-infected EPCs, whereas these genes returned in steady state when cells were exposed to sustained doses of l-arg. This mechanism may have broad therapeutic applications in tissue ischemia, angiogenesis, immune response, and sepsis. PMID:18595894

  17. Endothelial progenitor cells and revascularization following stroke.

    Science.gov (United States)

    Ma, Feifei; Morancho, Anna; Montaner, Joan; Rosell, Anna

    2015-10-14

    Brain injury after ischemia induces the mobilization of endothelial progenitor cells (EPCs), a population of bone marrow-derived cells with angio-vasculogenic capabilities. These cells have been also tested in pre-clinical models and proposed for neurorepair therapy aiming to treat patients in the delayed phases of stroke disease. Promising results in the pre-clinical field encourage the translation into a clinical therapeutic approach. In this review, we will describe EPCs actions for enhanced revascularization and neurorepair, which on one hand are by their direct incorporation into new vascular networks/structures or by direct cell-cell interactions with other brain cells, but also to indirect cell-cell communication thorough EPCs secreted growth factors. All these actions contribute to potentiate neurovascular remodeling and neurorepair. The data presented in this review encourages for a deep understanding of the mechanisms of the cross-talks between EPCs and other brain and progenitor cells, which deserves additional investigations and efforts that may lead to new EPCs-based therapies for stroke patients. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke. PMID:25725381

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

    International Nuclear Information System (INIS)

    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

  19. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  1. 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.

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

    Science.gov (United States)

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

    2016-08-01

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

  3. 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...... whether the numbers of EPC derived from peripheral blood mononuclear cells is influenced by a multifactorial treatment strategy....

  4. 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

  5. Morphogenesis of the lymphatic vasculature: A focus on new progenitors and cellular mechanisms important for constructing lymphatic vessels.

    Science.gov (United States)

    Kazenwadel, Jan; Harvey, Natasha L

    2016-03-01

    Lymphatic vessels serve crucial roles in the regulation of tissue fluid homeostasis, dietary lipid absorption and immune cell trafficking. Defects in lymphatic vessel morphogenesis and function have been associated with lymphedema, obesity, hypertension and tumour metastasis. Morphogenetic events important for construction of the lymphatic vasculature during development include the specification and emergence of lymphatic endothelial progenitor cells, their differentiation and assembly into interconnected vessels and vascular remodeling, ultimately giving rise to a functional vascular network. Despite the embryonic origins of lymphatic endothelial progenitor cells being long debated, work performed over the last decade had overwhelmingly supported at least a great majority of progenitor cells arising from the venous vasculature. Here, we review the most recent advances in the field of lymphatic vessel morphogenesis, with a focus on studies that have identified novel sources of embryonic lymphatic endothelial progenitor cells, together with the cellular mechanisms by which lymphatic vessels are initially assembled. PMID:26228815

  6. 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.

  7. What Is Vascular Disease?

    Science.gov (United States)

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

  8. Diabetes and Vascular Disease

    Science.gov (United States)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  10. 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.

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

    OpenAIRE

    Gulati, Rajiv; Simari, Robert D.

    2009-01-01

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

  12. 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; Østergaard, Mikkel; Nielsen, Hans Jørgen; Johansen, Julia Sidenius

    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 (TNFα) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNFα inhibitor therapy (infliximab, n=38; etanercept, n=8...

  13. 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; Østergaard, Mikkel; Nielsen, H.J.; Johansen, J.S.

    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...

  14. 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; Pedersen, Susanne Juhl; Hetland, Merete Lund; Østergaard, Mikkel; Johansen, Julia Sidenius

    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 (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...

  15. 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.

  16. Embryonic Heart Progenitors and Cardiogenesis

    Science.gov (United States)

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

    2013-01-01

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

  17. 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.

  18. The Pulmonary Circulation and Exercise Responses in the Elderly

    OpenAIRE

    Taylor, Bryan J.; Johnson, Bruce D.

    2010-01-01

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

  19. Engineered human vascularized constructs accelerate diabetic wound healing.

    Science.gov (United States)

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

    2016-09-01

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

  20. Retina vascular network recognition

    Science.gov (United States)

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

    1993-09-01

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

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

    OpenAIRE

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

    2012-01-01

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

  2. The matrix protein CCN1 (CYR61) promotes proliferation, migration and tube formation of endothelial progenitor cells

    International Nuclear Information System (INIS)

    Neovascularization and re-endothelialization relies on circulating endothelial progenitor cells (EPCs), but their recruitment and angiogenic roles are subjected to regulation by the vascular microenvironment, which remains largely unknown. The present study was designed to investigate the effects of mature ECs and matrix protein CCN1 on the properties of EPCs. In a coculture system, effects of ECs on proliferation, migration and participation in tube-like formation of EPCs were evaluated, and functional assays were employed to identify the exact role of CCN1 in EPCs vitality and function. We demonstrated that ECs, as an indispensable part of the cellular milieu, significantly promoted the proliferation, migration and tube formation activities of EPCs, and more importantly, CCN1 was potentially involved in such effects of ECs. Expression of CCN1 in EPCs was significantly increased by serum, VEGF, ECs-cocultivation and ECs conditioned medium. Moreover, Ad-CCN1-mediated overexpression of CCN1 directly enhanced migration and tube formation of EPCs, whereas silencing of endogenous CCN1 in EPCs inhibits cell functions. Furthermore, CCN1 induced the expressions of chemokines and growth factors, such as MCP-1 and VEGF, suggesting a complex interaction between those proangiogenic factors. Our data suggest that matrix protein CCN1 may play an important role in microenvironment-mediated biological properties of EPCs

  3. 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...

  4. Vascular corrosion casting of human heart

    Directory of Open Access Journals (Sweden)

    J. Vasudeva Reddy

    2013-06-01

    Full Text Available Variation in the morphological pattern of coronary arteries and their major branches is an important factor in the assessment and treatment of coronary heart disease. Detailed knowledge of the blood supply of the heart is necessary today because of the wider practice of cardiac surgery, and also for better understanding of the anomalous branches, anastomosis and dominance pattern in circulation caused by coronary vasculature. We utilized 80 human heart specimens and found right dominance in 69 specimens, left dominance in 9 specimens and balanced type of circulation in 2 specimens. We observed anastomosis between the major arteries in arteriogram but in vascular corrosion method we did not found because cast substance interpretation to minor vessels is too difficult. The present study acknowledges about Coronary vascular pattern, circulatory dominance of the arteries and by using the vascular corrosion method. [Int J Res Med Sci 2013; 1(3.000: 237-239

  5. Society for Vascular Medicine

    Science.gov (United States)

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

  6. Strategic Plan for Lung Vascular Research

    Science.gov (United States)

    Erzurum, Serpil; Rounds, Sharon I.; Stevens, Troy; Aldred, Micheala; Aliotta, Jason; Archer, Stephen L.; Asosingh, Kewal; Balaban, Robert; Bauer, Natalie; Bhattacharya, Jahar; Bogaard, Harm; Choudhary, Gaurav; Dorn, Gerald W.; Dweik, Raed; Fagan, Karen; Fallon, Michael; Finkel, Toren; Geraci, Mark; Gladwin, Mark T.; Hassoun, Paul M.; Humbert, Marc; Kaminski, Naftali; Kawut, Steven M.; Loscalzo, Joseph; McDonald, Donald; McMurtry, Ivan F.; Newman, John; Nicolls, Mark; Rabinovitch, Marlene; Shizuru, Judy; Oka, Masahiko; Polgar, Peter; Rodman, David; Schumacker, Paul; Stenmark, Kurt; Tuder, Rubin; Voelkel, Norbert; Sullivan, Eugene; Weinshilboum, Richard; Yoder, Mervin C.; Zhao, Yingming; Gail, Dorothy; Moore, Timothy M.

    2010-01-01

    The Division of Lung Diseases of the National Heart, Lung, and Blood Institute, with the Office of Rare Diseases Research, held a workshop to identify priority areas and strategic goals to enhance and accelerate research that will result in improved understanding of the lung vasculature, translational research needs, and ultimately the care of patients with pulmonary vascular diseases. Multidisciplinary experts with diverse experience in laboratory, translational, and clinical studies identified seven priority areas and discussed limitations in our current knowledge, technologies, and approaches. The focus for future research efforts include the following: (1) better characterizing vascular genotype–phenotype relationships and incorporating systems biology approaches when appropriate; (2) advancing our understanding of pulmonary vascular metabolic regulatory signaling in health and disease; (3) expanding our knowledge of the biologic relationships between the lung circulation and circulating elements, systemic vascular function, and right heart function and disease; (4) improving translational research for identifying disease-modifying therapies for the pulmonary hypertensive diseases; (5) establishing an appropriate and effective platform for advancing translational findings into clinical studies testing; and (6) developing the specific technologies and tools that will be enabling for these goals, such as question-guided imaging techniques and lung vascular investigator training programs. Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes. PMID:20833821

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-12-31

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

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

    Institute of Scientific and Technical Information of China (English)

    郭敬; 王烈

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  10. 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.

  11. Endothelial progenitor cells in atherosclerosis

    OpenAIRE

    Du, Fuyong; Zhou, Jun; Gong, Ren; Huang, Xiao; Pansuria, Meghana; Virtue, Anthony; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs’ population and improvement of vascula...

  12. Mobilization of human hematopoietic stem/progenitor-enriched CD34+ cells into peripheral blood during stress related to ischemic stroke.

    Directory of Open Access Journals (Sweden)

    M Z Ratajczak

    2006-06-01

    Full Text Available The bone marrow-derived stem/progenitor cells were demonstrated to play an important role in a regeneration of damaged tissue. Based on these observations we asked whether the stroke-related stress triggers mobilization of stem/progenitor cells from the bone marrow into the peripheral blood, which subsequently could contribute to regeneration of damaged organs. To address this issue, the peripheral blood samples were harvested from patients with ischemic stroke during the first 24 hrs as well as after the 48 (2nd day and 144 hrs (6th day since the manifestation of symptoms. In these patients we evaluated the percentage of hematopoietic stem/progenitor-enriched CD34+ cells by employing flow cytometry and the number of hematopoietic progenitor cells for the granulocyto-monocytic (CFU-GM and erythroid (BFU-E-lineages circulating in peripheral blood. We concluded that stress related to ischemic stroke triggers the mobilization of hematopoietic stem/progenitor cells from the bone marrow into peripheral blood. These circulating stem/progenitor cells may play an important role in the process of regeneration of the ischemic tissue.

  13. Sox17 Promotes Cell Cycle Progression and Inhibits TGF-β/Smad3 Signaling to Initiate Progenitor Cell Behavior in the Respiratory Epithelium

    OpenAIRE

    Lange, Alexander W.; Keiser, Angela R.; Wells, James M.; Zorn, Aaron M; Whitsett, Jeffrey A.

    2009-01-01

    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 ...

  14. Detrimental effects of Bartonella henselae are counteracted by l-arginine and nitric oxide in human endothelial progenitor cells

    OpenAIRE

    Salvatore, Paola; Casamassimi, Amelia; Sommese, Linda; Fiorito, Carmela; Ciccodicola, Alfredo; Rossiello, Raffaele; Avallone, Bice; Grimaldi, Vincenzo; Costa, Valerio; Rienzo, Monica; Colicchio, Roberta; Williams-Ignarro, Sharon; Pagliarulo, Caterina; Prudente, Maria Evelina; Abbondanza, Ciro

    2008-01-01

    The recruitment of circulating endothelial progenitor cells (EPCs) might have a beneficial effect on the clinical course of several diseases. Endothelial damage and detachment of endothelial cells are known to occur in infection, tissue ischemia, and sepsis. These detrimental effects in EPCs are unknown. Here we elucidated whether human EPCs internalize Bartonella henselae constituting a circulating niche of the pathogen. B. henselae invades EPCs as shown by gentamicin protection assays and t...

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

    OpenAIRE

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

    2012-01-01

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

  16. Surface-modified hyaluronic acid hydrogels to capture endothelial progenitor cells†‡

    OpenAIRE

    Camci-Unal, Gulden; Aubin, Hug; Ahari, Amirhossein Farajzadeh; Bae, Hojae; Nichol, Jason William; Khademhosseini, Ali

    2010-01-01

    A major challenge to the effective treatment of injured cardiovascular tissues is the promotion of endothelialization of damaged tissues and implanted devices. For this reason, there is a need for new biomaterials that promote endothelialization to enhance vascular repair. The goal of this work was to develop antibody-modified polysaccharide-based hydrogels that could selectively capture endothelial progenitor cells (EPCs). We showed that CD34 antibody immobilization on hyaluronic acid (HA) h...

  17. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    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 86Rb and 9-microns spheres labeled with 141Ce 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 (AVDO2) 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

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

    Directory of Open Access Journals (Sweden)

    Stephanie Hum

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

  19. Human Adipose Stromal Vascular Cell Delivery in a Fibrin Spray

    Science.gov (United States)

    Zimmerlin, Ludovic; Rubin, J. Peter; Pfeifer, Melanie E.; Moore, L.R.; Donnenberg, Vera S.; Donnenberg, Albert D.

    2014-01-01

    Background Adipose tissue represents a practical source of autologous mesenchymal stromal cells (MSC) and vascular-endothelial progenitor cells, available for regenerative therapy without in vitro expansion. One of the problems confronting the therapeutic application of such cells is how to immobilize them at the wound site. Here, we evaluated in vitro the growth and differentiation of human adipose stromal vascular fraction (SVF) cells after delivery using a fibrin spray system. Methods SVF cells were harvested from four human adult patients undergoing elective abdominoplasty using the LipiVage™ system. After collagenase digestion, mesenchymal and endothelial progenitor cells (pericytes, supra-adventitial stromal cells, endothelial progenitors) were quantified by flow cytometry before culture. SVF cells were applied to culture vessels using the Tisseel™ fibrin spray system. SVF cell growth and differentiation was documented by immunofluorescence staining and photomicrography. Results SVF cells remained viable following application and were expanded up to three weeks, when they reached confluence and adipogenic differentiation. Under angiogenic conditions, SVF cells formed endothelial (vWF+, CD31+ and CD34+) tubules surrounded by CD146+ and α-SMA+ perivascular/stromal cells. Discussion Human adipose tissue is a rich source of autologous stem cells, which are readily available for regenerative applications such as wound healing, without in vitro expansion. Our results indicate that mesenchymal and endothelial progenitor cells, prepared in a closed system from unpassaged lipoaspirate samples, retain their growth and differentiation capacity when applied and immobilized on a substrate using a clinically approved fibrin sealant spray system. PMID:23260090

  20. Mesenchymal markers on human adipose stem/progenitor cells

    Science.gov (United States)

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    The stromal-vascular fraction (SVF) of adipose tissue is a rich source of multipotent stem cells. We and others have described 3 major populations of stem/progenitor cells in this fraction, all closely associated with small blood vessels: endothelial progenitor cells (EPC, CD45−/CD31+/CD34+), pericytes (CD45−/CD31−/CD146+) and supra-adventitial adipose stromal cells (SA-ASC, CD45−/CD31−/CD146−/CD34+). EPC are luminal, pericytes are adventitial and SA-ASC surround the vessel like a sheath. The multipotency of the pericytes and SA-ASC compartments is strikingly similar to that of CD45−/CD34−/CD73+/CD105+/CD90+ bone marrow-derived mesenchymal stem cells (BM-MSC). Here we determine the extent to which this mesenchymal expression pattern is expressed on the 3 adipose stem/progenitor populations. Eight independent adipose tissue samples were analyzed in a single tube (CD105-FITC/CD73-PE/CD146-PETXR/CD14-PECY5/CD33-PECY5/CD235A-PECY5/CD31-PECY7/CD90-APC/CD34-A700/CD45-APCCY7/DAPI). Adipose EPC were highly proliferative with 14.3±2.8% (mean ± SEM) having >2N DNA. About half (53.1±7.6%) coexpressed CD73 and CD105, and 71.9±7.4% expressed CD90. Pericytes were less proliferative (8.2±3.4% >2N DNA) with a smaller proportion (29.6±6.9% CD73+/CD105+, 60.5±10.2% CD90+) expressing mesenchymal associated markers. However, the CD34+ subset of CD146+ pericytes, were both highly proliferative (15.1±3.6% with >2N DNA) and of uniform mesenchymal phenotype (93.3±3.7% CD73+/CD105+, 97.8±0.7% CD90+), suggesting transit amplifying progenitor cells. SA-ASC were the least proliferative (3.7 ± 0.8%>2N DNA) but were also highly mesenchymal in phenotype (94.4±3.2% CD73+/CD105+, 95.5±1.2% CD90+). These data imply a progenitor/progeny relationship between pericytes and SA-ASC, the most mesenchymal of SVF cells. Despite phenotypic and functional similarities to BM-MSC, SA-ASC are distinguished by CD34 expression. PMID:23184564

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

    Science.gov (United States)

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

    2014-07-01

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

  2. Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells.

    Science.gov (United States)

    Hirakawa, Satoshi; Hong, Young-Kwon; Harvey, Natasha; Schacht, Vivien; Matsuda, Kant; Libermann, Towia; Detmar, Michael

    2003-02-01

    In mammals, the lymphatic vascular system develops by budding of lymphatic progenitor endothelial cells from embryonic veins to form a distinct network of draining vessels with important functions in the immune response and in cancer metastasis. However, the lineage-specific molecular characteristics of blood vascular versus lymphatic endothelium have remained poorly defined. We isolated lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) by immunomagnetic isolation directly from human skin. Cultured LECs but not BVECs expressed the lymphatic markers Prox1 and LYVE-1 and formed LYVE-1-positive vascular tubes after implantation in vivo. Transcriptional profiling studies revealed increased expression of several extracellular matrix and adhesion molecules in BVECs, including versican, collagens, laminin, and N-cadherin, and of the growth factor receptors endoglin and vascular endothelial growth factor receptor-1/Flt-1. Differential immunostains of human skin confirmed the blood vessel-specific expression of these genes. During embryonic development, endoglin expression was gradually down-regulated on lymphatic endothelium whereas vascular endothelial growth factor receptor-1 was absent from lymphatics. We also identified several genes with specific expression in LECs. These results demonstrate that some lineage-specific genes are only expressed during distinct developmental stages and they identify new molecular markers for blood vascular and lymphatic endothelium with important implications for future studies of vascular development and function. PMID:12547715

  3. Chronic granulomatous disease. Expression of the metabolic defect by in vitro culture of bone marrow progenitors.

    OpenAIRE

    Newburger, P E; Kruskall, M S; Rappeport, J M; Robinson, S H; Chovaniec, M E; Cohen, H J

    1980-01-01

    Chronic granulomatous disease (CGD), an often fatal syndrome of recurrent infections results from the inability of patients' peripheral blood phagocytic leukocytes to generate superoxide despite otherwise normal phagocytic functions such as ingestion and degranulation. Circulating granulocytes and monocytes are the progeny of bone marrow progenitor cells, colony-forming units in culture. We compared the function of cells grown in two different in vitro cuture systems from the bone marrow of a...

  4. Bone marrow-derived progenitor cells in de novo liver regeneration in liver transplant.

    Science.gov (United States)

    Lee, Sung-Gyu; Moon, Sung-Hwan; Kim, Hee-Je; Lee, Ji Yoon; Park, Soon-Jung; Chung, Hyung-Min; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Hojong; Kwon, Tae-Won; Cho, Yong-Pil

    2015-09-01

    The study was designed (1) to examine the hypothesis that circulating progenitor cells play a role in the process of de novo regeneration in human liver transplants and that these cells arise from a cell population originating in, or associated with, the bone marrow and (2) to investigate whether the transplanted liver volume has an effect on the circulating recipient-derived progenitor cells that generate hepatocytes during this process. Clinical data and liver tissue characteristics were analyzed in male individuals who underwent sex-mismatched adult-to-adult living donor liver transplantation using dual left lobe grafts. Dual left lobe grafts were examined at the time of transplantation and 19 to 27 days after transplantation. All recipients showed recovery of normal liver function and a significant increase in the volume of the engrafted left lobes after transplantation. Double staining for a Y-chromosome probe and the CD31 antigen showed the presence of hybrid vessels composed of recipient-derived cells and donor cells within the transplanted liver tissues. Furthermore, CD34-expressing cells were observed commingling with Y-chromosome+ cells. The ratio of recipient-derived vessels and the number of Y+ CD34+ cells tended to be higher when smaller graft volumes underwent transplantation. These findings suggest that the recruitment of circulating bone marrow-derived progenitor cells could contribute to vessel formation and de novo regeneration in human liver transplants. Moreover, graft volume may be an important determinant for the active mobilization of circulating recipient-derived progenitor cells and their contribution to liver regeneration. PMID:25761987

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

    OpenAIRE

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

    2007-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  8. Engineering vascular development for tissue regeneration

    OpenAIRE

    Rivron, Nicolas Clemens

    2010-01-01

    Tissue engineering and regenerative medicine aim at restoring a damaged tissue by recreating in vitro or promoting its regeneratin in vovo. The vasculature is central to these therapies for the irrigation of the defective tissue (oxygen, nutrients or circulating regenerative cells) and as an inductive, trophic embedded organ. This thesis describes the in vitro formation of biological vascular networks for tissue engineering and regenerative medicine applications. In a first part, we show the ...

  9. Collagen vascular disease

    Science.gov (United States)

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

  10. Heart and vascular services

    Science.gov (United States)

    ... branch of medicine that focuses on the cardiovascular system. ... Circulatory system; Vascular system; Cardiovascular system ... to diagnose, monitor or treat diseases of the circulatory and vascular system include: Cardiac CT for calcium scoring Cardiac MRI ...

  11. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  12. Transplanting oligodendrocyte progenitors into the adult CNS

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, R.J.M.; Blakemore, W.F. [Medical Research Council, Cambridge (United Kingdom)]|[Cambridge Univ. (United Kingdom). Dept. of Clinical Veterinary Medicine

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author).

  13. How to Prevent Vascular Disease

    Science.gov (United States)

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

  14. Melatonin differentially affects vascular blood flow in humans

    OpenAIRE

    Cook, Jonathan S.; Sauder, Charity L.; Ray, Chester A.

    2010-01-01

    Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial...

  15. Deleterious effects of tributyltin on porcine vascular stem cells physiology.

    Science.gov (United States)

    Bernardini, Chiara; Zannoni, Augusta; Bertocchi, Martina; Bianchi, Francesca; Salaroli, Roberta; Botelho, Giuliana; Bacci, Maria Laura; Ventrella, Vittoria; Forni, Monica

    2016-01-01

    The vascular functional and structural integrity is essential for the maintenance of the whole organism and it has been demonstrated that different types of vascular progenitor cells resident in the vessel wall play an important role in this process. The purpose of the present research was to observe the effect of tributyltin (TBT), a risk factor for vascular disorders, on porcine Aortic Vascular Precursor Cells (pAVPCs) in term of cytotoxicity, gene expression profile, functionality and differentiation potential. We have demonstrated that pAVPCs morphology deeply changed following TBT treatment. After 48h a cytotoxic effect has been detected and Annexin binding assay demonstrated that TBT induced apoptosis. The transcriptional profile of characteristic pericyte markers has been altered: TBT 10nM substantially induced alpha-SMA, while, TBT 500nM determined a significant reduction of all pericyte markers. IL-6 protein detected in the medium of pAVPCs treated with TBT at both doses studied and with a dose response. TBT has interfered with normal pAVPC functionality preventing their ability to support a capillary-like network. In addition TBT has determined an increase of pAVPC adipogenic differentiation. In conclusion in the present paper we have demonstrated that TBT alters the vascular stem cells in terms of structure, functionality and differentiating capability, therefore effects of TBT in blood should be deeply explored to understand the potential vascular risk associated with the alteration of vascular stem cell physiology. PMID:26965667

  16. 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.

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

    OpenAIRE

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

    2008-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

  19. The progenitors of stripped-envelope supernovae

    Science.gov (United States)

    Elias-Rosa, N.

    2013-05-01

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

  20. Progenitor Cells and Podocyte Regeneration

    OpenAIRE

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

  2. 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...

  3. VEGF-sdf1 recruitment of CXCR7+ bone marrow progenitors of liver sinusoidal endothelial cells promotes rat liver regeneration.

    Science.gov (United States)

    DeLeve, Laurie D; Wang, Xiangdong; Wang, Lei

    2016-05-01

    In liver injury, recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (sprocs) is necessary for normal liver regeneration. Hepatic vascular endothelial growth factor (VEGF) is a central regulator of the recruitment process. We examine whether stromal cell-derived factor 1 [sdf1, or CXC ligand 12 (CXCL12)] acts downstream from VEGF to mediate recruitment of BM sprocs, what the sdf1 receptor type [CXC receptor (CXCR)-4 or CXCR7] is on sprocs, and whether sdf1 signaling is required for normal liver regeneration. Studies were performed in the rat partial hepatectomy model. Tracking studies of BM sprocs were performed in wild-type Lewis rats that had undergone BM transplantation from transgenic enhanced green fluorescent protein-positive Lewis rats. Knockdown studies were performed using antisense oligonucleotides (ASOs). Expression of sdf1 doubles in liver and liver sinusoidal endothelial cells (LSECs) after partial hepatectomy. Upregulation of sdf1 expression increases proliferation of sprocs in the BM, mobilization of CXCR7(+) BM sprocs to the circulation, and engraftment of CXCR7(+) BM sprocs in the liver and promotes liver regeneration. Knockdown of hepatic VEGF with ASOs decreases hepatic sdf1 expression and plasma sdf1 levels. When the effect of VEGF knockdown on sdf1 is offset by infusion of sdf1, VEGF knockdown-induced impairment of BM sproc recruitment after partial hepatectomy is completely attenuated and liver regeneration is normalized. These data demonstrate that the VEGF-sdf1 pathway regulates recruitment of CXCR7(+) BM sprocs to the hepatic sinusoid after partial hepatectomy and is required for normal liver regeneration. PMID:26939868

  4. 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

  5. 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

  6. 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.

  7. 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.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  9. 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.

  10. Intravascular Ultrasound and its Use in Vascular Interventional Radiology

    International Nuclear Information System (INIS)

    Intravascular ultrasound has become in invasive vascular radiology in the last decade the important part of diagnostic and also therapeutic procedures in management of vascular diseases. The basic possibilities for the use of IVUS include diagnostic procedures in vascular pathology assessment and therapeutic indications in the field of peripheral vascular interventions (PVI). Unlike other image modalities (CT, MRI, ultrasound) IVUS enables gather unique image in real timeright from the vessel lumen, what helps to add important information regarding vessel wall, plate morphology, thrombi and cross-sectional vessel area. After initial use of intravascular ultrasound in coronary circulation, using IVUS is nowadays widely extended especially in aortic diseases, carotid and renal arteries and arteries of the lower extremities. This review article summarizes possibilities of intravascular ultrasound utilization in diagnostic process and therapy from peripheral vascular diseases up to thoracoabdominal aorta diseases and our experience with this new diagnostic modality. (author)

  11. A Multipotent Progenitor Domain Guides Pancreatic Organogenesis

    OpenAIRE

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

    2007-01-01

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

  12. Imaging Pediatric Vascular Lesions

    Science.gov (United States)

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  13. Imaging Pediatric Vascular Lesions.

    Science.gov (United States)

    Nguyen, Tuyet A; Krakowski, Andrew C; Naheedy, John H; Kruk, Peter G; Friedlander, Sheila Fallon

    2015-12-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  14. 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 ...

  15. Vascularity in thyroid neoplasms

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jun Sik Lee

    2014-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

    Barr, R Graham

    2011-01-01

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

  19. Specialized mouse embryonic stem cells for studying vascular development

    Directory of Open Access Journals (Sweden)

    Glaser DE

    2014-10-01

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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Ken Arai

    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.

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

    Science.gov (United States)

    Maki, Takakuni; Liang, Anna C.; Miyamoto, Nobukazu; Lo, Eng H.; Arai, Ken

    2013-01-01

    White matter dysfunction is an important part of many CNS disorders including multiple sclerosis (MS) 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 (SGZ) 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 (ECM), cerebrospinal fluid (CSF)) 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. PMID:24421755

  3. 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.

  4. Poikiloderma vasculare atrophicans

    OpenAIRE

    Padmavathy L; Prasad PVS; Prasanna K; Rao L

    1994-01-01

    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.

  5. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt; Bak, M; Vach, W; Rose, C

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  6. [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. PMID:26597554

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

    Institute of Scientific and Technical Information of China (English)

    张宾辉; 代建峰; 陈眉; 丰素娟

    2004-01-01

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

  8. Progenitors of core-collapse supernovae

    CERN Document Server

    Smartt, Stephen J

    2009-01-01

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

  9. Cardiac nerve growth factor overexpression induces bone marrow–derived progenitor cells mobilization and homing to the infarcted heart

    OpenAIRE

    Meloni, Marco; Cesselli, Daniela; Caporali, Andrea; Mangialardi, Giuseppe; Avolio, Elisa; Reni, Carlotta; Fortunato, Orazio; Martini, Stefania; Madeddu, Paolo; Valgimigli, Marco; Nikolaev, Evgeni; Kaczmarek, Leszek; Angelini, Gianni D.; Beltrami, Antonio P; Emanueli, Costanza

    2015-01-01

    Reparative response by bone marrow (BM)-derived progenitor cells (PCs) to ischemia is a multistep process that comprises the detachment from the BM endosteal niche through activation of osteoclasts and proteolytic enzymes (such as matrix metalloproteinases (MMPs)), mobilization to the circulation, and homing to the injured tissue. We previously showed that intramyocardial nerve growth factor gene transfer (NGF-GT) promotes cardiac repair following myocardial infarction (MI) in mice. Here, we ...

  10. 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

  11. Pediatric vascular access

    International Nuclear Information System (INIS)

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

  12. Pediatric vascular access

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-05-15

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

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

    Directory of Open Access Journals (Sweden)

    Sirpa Loukovaara

    2015-07-01

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

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

    Science.gov (United States)

    Loukovaara, Sirpa; Gucciardo, Erika; Repo, Pauliina; Lohi, Jouko; Salven, Petri; Lehti, Kaisa

    2015-01-01

    Purpose Pathological vascular differentiation in retinal vein occlusion (RVO)-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or endothelial progenitor cell activity has not been studied in this disease. Methods Vitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC) adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin (PDPN), and prospero-related homeobox protein 1 (Prox-1). Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67) and expression of the stem cell marker CD117. Results The specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity. Conclusions Intraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO. PMID:26327908

  15. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

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

  16. 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.

  17. 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.

  18. 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.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Lucia Cuppini

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

  1. 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; Nielsen, C T; Halberg, P; Karlsmark, T; Heegaard, Niels Henrik Helweg; Jacobsen, Søren

    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...

  2. Opposing effects of monomeric and pentameric C-reactive protein on endothelial progenitor cells

    OpenAIRE

    Ahrens, I.; Domeij, H.; Eisenhardt, S. U.; Topcic, D.; Albrecht, M.; Leitner, E.; Viitaniemi, K.; Jowett, J B; Lappas, M.; Bode, C.; Haviv, I.; Peter, K

    2011-01-01

    C-reactive protein (CRP) has been linked to the pathogenesis of atherosclerosis. The dissociation of native, pentameric (p)CRP to monomeric (m)CRP on the cell membrane of activated platelets has recently been demonstrated. The dissociation of pCRP to mCRP may explain local pro-inflammatory reactions at the site of developing atherosclerotic plaques. As a biomarker, pCRP predicts cardiovascular adverse events and so do reduced levels and function of circulating endothelial progenitor cells (EP...

  3. Congenital Vascular Malformation

    Science.gov (United States)

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

  4. Vascular Access for Hemodialysis

    Science.gov (United States)

    ... for short-term use. [ Top ] What is an arteriovenous fistula? An AV fistula is a connection, made by ... to remove and return blood during hemodialysis. An arteriovenous (AV) fistula is a connection, made by a vascular surgeon, ...

  5. Heart and vascular services

    Science.gov (United States)

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

  6. Management of Vascular Malformations

    Directory of Open Access Journals (Sweden)

    Sadanori Akita, MD, PhD

    2014-03-01

    Conclusions: Treatment of vascular malformations is an integral part of multidisciplinary approaches. Venous malformations are more frequent in combination surgery, and if there are fewer complications, the patients’ satisfaction increases.

  7. Vascular Effects of Histamine.

    Science.gov (United States)

    Ebeigbe, Anthony B; Talabi, Olufunke O

    2014-01-01

    Four subtypes of receptors (H1, H2, H3 and H4) mediate the actions of histamine. In the vascular wall, the effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype located on presynaptic neurones. Alterations in vascular responses to histamine are associated with experimental as well as a human form of hypertension, suggesting a role for histanine in cardiovascular regulation. PMID:26196559

  8. Digital vascular imaging (DVI)

    International Nuclear Information System (INIS)

    Digitization of the video signals from an image intensifier/TV chain, followed by subtraction, contrast enchancement and reconversion to analogue signals, enables high quality angiographic images to be obtained from an intravenous injection of contrast medium. As the examination is basically noninvasive it can be used in outpatients. The possibilities of Digital Vascular Imaging are demonstrated by images obtained from the various vascular regions using a triple-mode 14 in. image intensifier with a Plumbicon. TV tube. (Auth.)

  9. Thrombolysis in vascular surgery

    OpenAIRE

    Smith, Linn

    2015-01-01

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

  10. [Zaidemberg's vascularized radial graft].

    Science.gov (United States)

    Saint-Cast, Y

    2010-12-01

    In 1991, Carlos Zaidemberg described a new technique to repair scaphoid non-unions with a vascularized bone graft harvested from the radial styloid process. An anatomic study based on 30 dissections after colorized latex injection established the constancy of the radial styloid process's artery, while showing that its origin, course and length were subject to variations. In a retrospective series of 38 cases over a period of 10 years, the vascularized bone graft was indicated for: (1) scaphoid non-union with the presence of avascular changes of the proximal fragment (23 cases); (2) failed prior reconstruction with bone graft and internal fixation (nine cases); (3) degenerative styloid-scaphoid arthritis (three cases); (4) fracture on Preiser dystrophy (three cases). The five steps of the simplified operative technique without dissection of the vascular pedicle include: (1) longitudinal dorso-radial approach, identification of the periosteal portion of the radial styloid process artery; (2) incision of the first and second compartments, longitudinal arthrotomy under the second compartment; (3) styloidectomy and transversal resection of the scaphoid non-union and sclerotic bone; (4) elevation of the vascularized bone graft; (5) transversal and radial insertion of the vascularized bone graft, osteosynthesis by two or three K-wire touching the scaphoid's radial edge. Scaphoid union was obtained in 33 cases out of 38. The only postoperative complications were two transient radial paresthesia. The standardized surgical procedure using vascularized bone graft harvested from the radial styloid process provides an efficient scaphoid reconstruction. PMID:21087882

  11. 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

  12. 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.

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

    Science.gov (United States)

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

    2016-03-01

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

  14. 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.

  15. Concepts in Assisted Circulation

    OpenAIRE

    Lefemine, Armand A.; Dunbar, Jacob; DeLucia, Anthony

    1986-01-01

    Assisted circulation by extracorporeal and extracardiac bypass techniques must be based on the requirements of the heart and of the total body, though these may differ. The cardiac problem in cardiogenic shock is more likely to be a biventricular problem demanding decompression of both sides. Extra pulmonary oxygenation should be avoided because of complexity in long-term use. Principles of assisted circulation may be applied in an extra-thoracic temporary manner or as an intracorporeal long-...

  16. In vivo identification of periodontal progenitor cells.

    Science.gov (United States)

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

    2013-08-01

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

  17. Binary progenitor models of type IIb supernovae

    NARCIS (Netherlands)

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

    2011-01-01

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

  18. GRB 011121 A Massive Star Progenitor

    CERN Document Server

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

    2002-01-01

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

  19. 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

  20. EMMPRIN-Mediated Induction of Uterine and Vascular Matrix Metalloproteinases during Pregnancy and in Response to Estrogen and Progesterone

    OpenAIRE

    Dang, Yiping; Li, Wei; Tran, Victoria; Khalil, Raouf A

    2013-01-01

    Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during p...

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

    Science.gov (United States)

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

    2016-08-01

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

  2. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    International Nuclear Information System (INIS)

    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 (MZAMS) 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 MZAMS 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 ∼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∝Mα, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) (α = –2.35). In particular, we find values of α outside the range –2.7 ≥ α ≥ –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 MMax > 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 minimum mass for core collapse between 7.0 and 7.8 M☉.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Ji Woong Han

    2013-04-01

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

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

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  6. Antioxidants and vascular health.

    Science.gov (United States)

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

    2015-12-15

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

  7. Human cerebral circulation. Positron emission tomography studies

    International Nuclear Information System (INIS)

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

  8. 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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

    Critser, Paul J.; Yoder, Mervin C.

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

  11. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

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

  12. 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.

  13. NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

    Science.gov (United States)

    Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

    2016-06-01

    Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease. PMID:26485210

  14. 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

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

    Science.gov (United States)

    Stone, H. L.; Sandler, H.

    1977-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  17. Doppler velocimetry with emphasis on the fetal cerebral circulation

    OpenAIRE

    Noordam, Marja

    1996-01-01

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

  18. Physiological modeling of tumor-affected renal circulation.

    OpenAIRE

    Bézy-Wendling, Johanne; Kretowski, Marek

    2008-01-01

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

  19. Human Fetal Progenitor Tenocytes for Regenerative Medicine.

    OpenAIRE

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

    2016-01-01

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

  20. BMP signaling in the nephron progenitor niche

    OpenAIRE

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

    2011-01-01

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

  1. Endothelial progenitor cells in hematologic malignancies.

    Science.gov (United States)

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

    2016-01-01

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

  2. TOX3 regulates neural progenitor identity.

    Science.gov (United States)

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

    2016-07-01

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

  3. Plant vascular development

    NARCIS (Netherlands)

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

    2016-01-01

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

  4. 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

  5. Vascularization of bone regeneration products in acute radiation sickness

    International Nuclear Information System (INIS)

    In 119 rabbits with acute radiation sickness the vascularization process in bone regeneration products was studied by microangiography. The formation of arteries and of bone structures was retarded in irradiated animals. The deficient formation of veins and capillaries did not cause conditions for venous blood circulation and resulted in a slow resorption of newly formed bone structures and gristle. That is one of the reasons for an extended healing process of fractures and for formation of false articulations in irradiated animals. (author)

  6. Vascular Endothelial Growth Factor, diagnostic and therapeutic aspects

    OpenAIRE

    Kusumanto, Yoka Hadiani

    2006-01-01

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

  7. Vascular manifestations of Behcet's disease

    Directory of Open Access Journals (Sweden)

    Regina Georgiyeva Goloeva

    2010-04-01

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

  8. 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1

    OpenAIRE

    Shimoda, Larissa A.

    2012-01-01

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

  9. The effect of the dietary constituent conjugated linoleic acid and homocysteine on vascular endothelial cell function

    OpenAIRE

    Coen, Paul Martin

    2004-01-01

    The interaction between circulating dietary constituents and the vascular endothelial monolayer is vital to the proper maintenance o f vascular homeostatic mechanisms, such as vasoregulation. Endothelial dysfunction with subsequent loss of vasoregulatory function are implicated in the early stages of atherosclerosis. Conjugated linoleic acid (CLA) and homocysteine are dietary constituents that have been implicated in the aetiology of atherosclerosis. CLA is the collective term used for po...

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

    Science.gov (United States)

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

    2006-02-01

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

  11. Asymmetric centrosome inheritance maintains neural progenitors in neocortex

    OpenAIRE

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

    2009-01-01

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

  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. Gamma Ray Burst progenitors - a case for helium star mergers

    OpenAIRE

    Belczynski, Krzysztof; Bulik, Tomasz; Rudak, Bronislaw

    2000-01-01

    Recently much work in Gamma-Ray Burst (GRB) studies was devoted to revealing the nature of outburst mechanism and to looking for GRB progenitors. Several types of progenitors were proposed for GRBs. Most promising objects are collapsars, compact object binaries, Helium star mergers and recently discussed supernovae. In this paper we consider four proposed binary star progenitors of GRBs: double neutron star (NS-NS), black hole neutron star (BH-NS), black hole white dwarf (BH-WD) mergers and H...

  14. iPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium.

    Science.gov (United States)

    Ja, Kp Myu Mia; Miao, Qingfeng; Zhen Tee, Nicole Gui; Lim, Sze Yun; Nandihalli, Manasi; J A Ramachandra, Chrishan; Mehta, Ashish; Shim, Winston

    2016-02-01

    We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 10(5) progenitors, cardiomyocytes or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Myocardial function was assessed at 2-week and 4-week post-infarction by using echocardiography and pressure-volume catheterization. Early myocardial remodelling was observed at 2-week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P EDV: 23.24 ± 5.01 μl, P EDV: 26.45 ± 5.69 μl, P EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2-(38.68 ± 7.34%) to 4-week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2-week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm(2) to 25.48 ± 2.08/mm(2) myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone. PMID:26612359

  15. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir;

    2015-01-01

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory...... mechanisms. Here, we comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state...... that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution....

  16. Cell culture: Progenitor cells from human brain after death

    Science.gov (United States)

    Palmer, Theo D.; Schwartz, Philip H.; Taupin, Philippe; Kaspar, Brian; Stein, Stuart A.; Gage, Fred H.

    2001-05-01

    Culturing neural progenitor cells from the adult rodent brain has become routine and is also possible from human fetal tissue, but expansion of these cells from postnatal and adult human tissue, although preferred for ethical reasons, has encountered problems. Here we describe the isolation and successful propagation of neural progenitor cells from human postmortem tissues and surgical specimens. Although the relative therapeutic merits of adult and fetal progenitor cells still need to be assessed, our results may extend the application of these progenitor cells in the treatment of neurodegenerative diseases.

  17. 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.

  18. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-05-01

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

  19. Pathophysiology of vascular dementia

    Directory of Open Access Journals (Sweden)

    Rizzo Claudia

    2009-11-01

    Full Text Available Abstract The concept of Vascular Dementia (VaD has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments that document the demographic data in a standardized manner and undertake a systematic effort to identify the underlying aetiology in each case. Increased effort should be targeted towards the concept of and criteria for Vascular Cognitive Impairment and Post-Stroke Dementia as well as for genetic factors involved, especially as these categories hold promise for early prevention and treatment.

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Pathophysiology of vascular dementia

    OpenAIRE

    Rizzo Claudia; Duro Giovanni; Iemolo Francesco; Castiglia Laura; Hachinski Vladimir; Caruso Calogero

    2009-01-01

    Abstract The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments th...

  2. Update on Vascular Dementia.

    Science.gov (United States)

    Khan, Ayesha; Kalaria, Raj N; Corbett, Anne; Ballard, Clive

    2016-09-01

    Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment. PMID:27502303

  3. Vascular Cambium Development

    Science.gov (United States)

    Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

    2015-01-01

    Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

  4. INTERNAL CIRCULATION ENVELOPES

    CERN Multimedia

    Mail Office

    2001-01-01

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

  5. Leukocytes are required for the trypsin-induced increase in lung vascular permeability.

    OpenAIRE

    Garcia-Szabo, R. R.; Johnson, A; Malik, A B

    1986-01-01

    The authors examined the role of leukocytes in mediating the increase in lung vascular permeability induced by trypsin infusion in the sheep lung lymph preparation. One group of sheep was challenged with an intravenous infusion of trypsin (4.5 mg/kg/hr). A second group was depleted of 80% of circulating granulocytes and of 48% of circulating lymphocytes by repeated injections of hydroxyurea several days prior to the trypsin infusion. Pulmonary lymph flow and transvascular protein clearance in...

  6. Bone Marrow Stress Decreases Osteogenic Progenitors.

    Science.gov (United States)

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

    2015-11-01

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

  7. Osteopontin Function and Interaction with Vascular Calcification and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Arnon Blum

    2012-12-01

    progenitors/stem cells unbalance may contribute for the vascular calcification. A better understanding of the mechanism that link between bones and blood vessels may open a new frontier to fight atherosclerosis and enhance blood vessel repair.

  8. Alterations in transcriptional responses associated with vascular aging

    Directory of Open Access Journals (Sweden)

    Oettgen Peter

    2009-05-01

    Full Text Available Abstract Vascular aging is an independent risk factor for cardiovascular disease that can occur in the absence of other traditional risk factors. Inflammation is a hallmark of vascular aging that ultimately leads to structural changes in the vessel wall including an increase in medial thickness and perivascular fibrosis. Several classes of transcription factors have been identified that participate in the regulation of cellular responses associated with vascular aging. Nuclear factor (NF-κB is the prototypic example of a transcriptional activator in the setting of inflammation, being activated in response to multiple inflammatory mediators including pro-inflammatory cytokines and bacterial endotoxin. In contrast, the activation of the nuclear hormone receptor and transcription factor peroxisome proliferator-activated receptor-alpha (PPAR-α results in its translocation from the cell surface to the nucleus where it exerts anti-inflammatory effects. Vascular aging is also associated with endothelial dysfunction. One important repair mechanism for improving endothelial function is the recruitment of endothelial progenitor cells (EPCs. In the setting of aging the number of EPCs diminishes which has been linked to a decrease in the activity and/or expression of the transcription factor hypoxia inducible factor (HIF-1 alpha. A change in the balance of the activity of pro-inflammatory transcription factors versus those that inhibit inflammation likely contributes to the process of vascular aging. The purpose of this review is to summarize our current knowledge of these age-related changes in transcriptional responses, and to discuss the therapeutic potential of targeting some of these factors.

  9. Radiosensitivities of immune organs' stromal progenitors

    International Nuclear Information System (INIS)

    By using the technique of culture of immuno-stromal progenitors in vitro, we studied their radiosensitivities after irradiation in various doses. The values of D0 and n of thymus, spleen and lymph node were 2.3 Gy and 1.5, 2.8 Gy and 1.2, 2.7 Gy and 1.4 respectively. The radiosensitivity of the CFU-F subgroups which formed dense colonies was significantly higher than that of loose colonies, when cultured in vitro

  10. The Progenitors of Core-Collapse Supernovae

    OpenAIRE

    Eldridge, J. J.; Tout, C. A.

    2004-01-01

    We present maps of the nature of single star progenitors of supernovae and their remnants in mass and metallicity space. We find our results are similar to others but we have gone further in varying the amount of mixing and using various mass-loss schemes to see how the maps change. We find that extra-mixing, in the form of convective overshooting, moves boundaries such as the minimum mass for a supernova or WR star to lower masses. We also find that the pre-WR mass-loss determines the shape ...

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

    OpenAIRE

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

    2013-01-01

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

  12. Peripheral vascular imaging

    International Nuclear Information System (INIS)

    Techniques for the evaluation of the cardiovascular system are among the oldest in nuclear medicine. Arm-to-arm circulation times were determined in humans using the naturally occurring radioactivity of radium. In 1948 artificially produced radioactive sodium was used to evaluate the circulation time through the heart in both normal subjects and patients with heart disease. This technique utilized an intravenous injection of sodium-24 into the antecubital vein of one arm and the generation of a graph of the count rate with a Geiger-Muller tube placed over the percordium as the radiolabeled blood passed through the chambers of the heart. This simple measurement had many components to it: a venous phase, a pulmonary circulation phase, and a phase for the cardiac chambers. Since this early work, the development of short-lived radiopharmaceuticals, advances in detection devices, and the introduction of computers into clinical nuclear medicine have permitted separation of these various components, allowing the study of venous, pulmonary, intracardiac, arterial, and capillary phases

  13. Sirtuins in vascular diseases: Emerging roles and therapeutic potential.

    Science.gov (United States)

    D'Onofrio, Nunzia; Vitiello, Milena; Casale, Rosario; Servillo, Luigi; Giovane, Alfonso; Balestrieri, Maria Luisa

    2015-07-01

    Silent information regulator-2 (Sir-2) proteins, or sirtuins, are a highly conserved protein family of histone deacetylases that promote longevity by mediating many of the beneficial effects of calorie restriction which extends life span and reduces the incidence of cancer, cardiovascular disease (CVD), and diabetes. Here, we review the role of sirtuins (SIRT1-7) in vascular homeostasis and diseases by providing an update on the latest knowledge about their roles in endothelial damage and vascular repair mechanisms. Among all sirtuins, in the light of the numerous functions reported on SIRT1 in the vascular system, herein we discuss its roles not only in the control of endothelial cells (EC) functionality but also in other cell types beyond EC, including endothelial progenitor cells (EPC), smooth muscle cells (SMC), and immune cells. Furthermore, we also provide an update on the growing field of compounds under clinical evaluation for the modulation of SIRT1 which, at the state of the art, represents the most promising target for the development of novel drugs against CVD, especially when concomitant with type 2 diabetes. PMID:25766107

  14. [How Treatable is Vascular Dementia?].

    Science.gov (United States)

    Mori, Etsuro

    2016-04-01

    Vascular dementia is an umbrella term, encompassing the pathological changes in the brain due to cerebrovascular disease that result in dementia. Vascular dementia is the second most common form of dementia, after Alzheimer's disease. In this paper, I outline the concept of vascular dementia, the key aspects of the disease that are yet to be clarified, and the current status of clinical trials. Assessing these factors, I discuss how treatable vascular dementia presently is. Use of the term'vascular dementia'is riddled with uncertainties regarding disease classification, and non-standardized diagnostic criteria. There are difficulties in determining the exact relationship between cerebrovascular pathology and cognitive impairment. The comorbid effects of Alzheimer's pathology in some individuals also present an obstacle to reliable clinical diagnosis, and hinder research into effective management approaches. Vascular dementia is preventable and treatable, as there are established primary and secondary prevention measures for the causative cerebrovascular diseases, such as vascular risk factor intervention, antiplatelet therapy, and anticoagulation, amongst others. However, unlike Alzheimer's disease, there are no established symptomatic treatments for vascular dementia. Clinical trials of cholinesterase inhibitors and memantine indicate that they produce small cognitive benefits in patients with vascular dementia, though the exact clinical significance of these is uncertain. Data are insufficient to support the widespread use of these drugs in vascular dementia. Rehabilitation and physical and cognitive exercise may be beneficial, but evidence of cognitive benefit and relief of neuropsychiatric symptoms due to exercise is lacking. PMID:27056862

  15. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    OpenAIRE

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark o...

  16. VIP and its homologous increase vascular conductance in certain endocrine and exocrine glands

    International Nuclear Information System (INIS)

    The effects of vasoactive intestinal peptide (VIP) and related structural homologues on tissue vascular conductances were investigated in anesthetized male rats. VIP, peptide histidine isoleucine (PHI), secretin, growth hormone-releasing factor (GHRF), gastric inhibitory peptide (GIP), or saline was infused intravenously over 4 min. Tissue blood flows were measured during this time by use of 141Ce-labeled microspheres. Circulating thyrotropin (TSH), triiodothyronine (T3), and thyroxine (T4) levels were determined before and at 20 min and 2 h after treatment. Marked increases in thyroid, pancreatic, and salivary gland vascular Cs occurred during peptide infusion with the order of potency correlating with the degree of structural homology to VIP. PHI and secretin produced maximal increases in vascular Cs, which were the same as those obtained with VIP. Circulating TSH, T3, and T4 levels were not different from values in saline-infused rats after peptide treatments that caused striking increases in thyroid vascular C. These observations indicate that the vascular beds of certain endocrine and exocrine glands are responsive to the vasodilatory action of VIP and related homologues with the order of potency corresponding to the degree of structural homology to VIP. These results are also consistent with the proposal that structural homologues of VIP act at the same vascular receptor as VIP. Alternative, the involvement of different vascular receptors, acting through the same mechanism at a level beyond the receptor site, cannot be excluded

  17. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Lavik, Erin B; Scherfig, Erik; Langer, Robert; Klassen, Henry J; Young, Michael J

    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....

  18. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors

    OpenAIRE

    Jiang, Huaqi; Edgar, Bruce A.

    2009-01-01

    In holometabolous insects, the adult appendages and internal organs form anew from larval progenitor cells during metamorphosis. As described here, the adult Drosophila midgut, including intestinal stem cells (ISCs), develops from adult midgut progenitor cells (AMPs) that proliferate during larval development in two phases. Dividing AMPs first disperse, but later proliferate within distinct islands, forming large cell clusters that eventually fuse during metamorphosis ...

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

    International Nuclear Information System (INIS)

    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

  20. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    Science.gov (United States)

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID:26141839

  1. 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.

  2. Abdominal Vascular Catastrophes.

    Science.gov (United States)

    Singh, Manpreet; Koyfman, Alex; Martinez, Joseph P

    2016-05-01

    Abdominal vascular catastrophes are among the most challenging and time sensitive for emergency practitioners to recognize. Mesenteric ischemia remains a highly lethal entity for which the history and physical examination can be misleading. Laboratory tests are often unhelpful, and appropriate imaging must be quickly obtained. A multidisciplinary approach is required to have a positive impact on mortality rates. Ruptured abdominal aortic aneurysm likewise may present in a cryptic fashion. A specific type of ruptured aneurysm, the aortoenteric fistula, often masquerades as the more common routine gastrointestinal bleed. The astute clinician recognizes that this is a more lethal variant of gastrointestinal hemorrhage. PMID:27133247

  3. 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.

  4. Microfluidic Technology in Vascular Research

    Directory of Open Access Journals (Sweden)

    A. D. van der Meer

    2009-01-01

    Full Text Available Vascular cell biology is an area of research with great biomedical relevance. Vascular dysfunction is involved in major diseases such as atherosclerosis, diabetes, and cancer. However, when studying vascular cell biology in the laboratory, it is difficult to mimic the dynamic, three-dimensional microenvironment that is found in vivo. Microfluidic technology offers unique possibilities to overcome this difficulty. In this review, an overview of the recent applications of microfluidic technology in the field of vascular biological research will be given. Examples of how microfluidics can be used to generate shear stresses, growth factor gradients, cocultures, and migration assays will be provided. The use of microfluidic devices in studying three-dimensional models of vascular tissue will be discussed. It is concluded that microfluidic technology offers great possibilities to systematically study vascular cell biology with setups that more closely mimic the in vivo situation than those that are generated with conventional methods.

  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. 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.

  7. 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.

  8. 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.

  9. Spinal vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Krings, Timo [University Hospital Aachen, Department of Neuroradiology, Aachen (Germany); University Hospital Aachen, Department of Neurosurgery, Aachen (Germany); Mull, Michael; Thron, Armin [University Hospital Aachen, Department of Neuroradiology, Aachen (Germany); Gilsbach, Joachim M. [University Hospital Aachen, Department of Neurosurgery, Aachen (Germany)

    2005-02-01

    Spinal vascular malformations are rare diseases that consist of true inborn cavernomas and arteriovenous malformations (including perimedullary fistulae, glomerular and juvenile AVMs) and presumably acquired dural arteriovenous fistulae. This review article gives an overview of the imaging features both on MRI and angiography, the differential diagnoses, the clinical symptomatology and the potential therapeutic approaches to these diseases. It is concluded that MRI is the diagnostic modality of first choice in suspected spinal vascular malformation and should be complemented by selective spinal angiography. Treatment in symptomatic patients offers an improvement in the prognosis, but should be performed in specialized centers. Patients with spinal cord cavernomas and perimedullary fistulae type I are surgical candidates. Dural arteriovenous fistulae can either be operated upon or can be treated by an endovascular approach, the former being a simple, quick and secure approach to obliterate the fistula, while the latter is technically demanding. In spinal arteriovenous malformations, the endovascular approach is the method of first choice; in selected cases, a combined therapy might be sensible. (orig.)

  10. Spinal vascular malformations

    International Nuclear Information System (INIS)

    Spinal vascular malformations are rare diseases that consist of true inborn cavernomas and arteriovenous malformations (including perimedullary fistulae, glomerular and juvenile AVMs) and presumably acquired dural arteriovenous fistulae. This review article gives an overview of the imaging features both on MRI and angiography, the differential diagnoses, the clinical symptomatology and the potential therapeutic approaches to these diseases. It is concluded that MRI is the diagnostic modality of first choice in suspected spinal vascular malformation and should be complemented by selective spinal angiography. Treatment in symptomatic patients offers an improvement in the prognosis, but should be performed in specialized centers. Patients with spinal cord cavernomas and perimedullary fistulae type I are surgical candidates. Dural arteriovenous fistulae can either be operated upon or can be treated by an endovascular approach, the former being a simple, quick and secure approach to obliterate the fistula, while the latter is technically demanding. In spinal arteriovenous malformations, the endovascular approach is the method of first choice; in selected cases, a combined therapy might be sensible. (orig.)

  11. Pulmonary vascular diseases.

    Science.gov (United States)

    Mélot, C; Naeije, R

    2011-04-01

    Diseases of the pulmonary vasculature are a cause of increased pulmonary vascular resistance (PVR) in pulmonary embolism, chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary arterial hypertension or decreased PVR in pulmonary arteriovenous malformations on hereditary hemorrhagic telangiectasia, portal hypertension, or cavopulmonary anastomosis. All these conditions are associated with a decrease in both arterial PO2 and PCO2. Gas exchange in pulmonary vascular diseases with increased PVR is characterized by a shift of ventilation and perfusion to high ventilation-perfusion ratios, a mild to moderate increase in perfusion to low ventilation-perfusion ratios, and an increased physiologic dead space. Hypoxemia in these patients is essentially explained by altered ventilation-perfusion matching amplified by a decreased mixed venous PO2 caused by a low cardiac output. Hypocapnia is accounted for by hyperventilation, which is essentially related to an increased chemosensitivity. A cardiac shunt on a patent foramen ovale may be a cause of severe hypoxemia in a proportion of patients with pulmonary hypertension and an increase in right atrial pressure. Gas exchange in pulmonary arteriovenous malformations is characterized by variable degree of pulmonary shunting and/or diffusion-perfusion imbalance. Hypocapnia is caused by an increased ventilation in relation to an increased pulmonary blood flow with direct peripheral chemoreceptor stimulation by shunted mixed venous blood flow. PMID:23737196

  12. 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.

  13. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets

    OpenAIRE

    Möhle, Robert; Green, David; Moore, Malcolm A. S.; Nachman, Ralph L.; Rafii, Shahin

    1997-01-01

    We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors. Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growt...

  14. 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.

  15. Modulation of 11β-Hydroxysteroid Dehydrogenase as a Strategy to Reduce Vascular Inflammation

    OpenAIRE

    Hadoke, Patrick W. F.; Kipari, Tiina; Seckl, Jonathan R; Chapman, Karen E.

    2013-01-01

    Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating leve...

  16. No effect of melatonin to modify surgical-stress response after major vascular surgery

    DEFF Research Database (Denmark)

    Kücükakin, B.; Wilhelmsen, M.; Lykkesfeldt, Jens;

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  17. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals

    OpenAIRE

    Yoder, Mervin C.; Mead, Laura E.; Prater, Daniel; Krier, Theresa R.; Mroueh, Karim N.; Li, Fang; Krasich, Rachel; Temm, Constance J.; Prchal, Josef T.; Ingram, David A.

    2007-01-01

    The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies “endothelial cell colony-forming units” (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast...

  18. Progenitor model of Cosmic Ray knee

    CERN Document Server

    Bijay, Biplab

    2014-01-01

    Primary energy spectrum of cosmic rays exhibits a knee at about $3$ PeV where a change in the spectral index occurs. Despite many efforts the origin of such a feature of the spectrum is not satisfactorily solved yet. Here in the framework of hypernova model of galactic cosmic ray origin it is proposed that the steepening of the spectrum beyond the knee may be a consequence of mass distribution of progenitor of cosmic ray source. The proposed model can account all the major observed features about cosmic rays without invoking any fine tuning to match flux or spectra at any energy point. The prediction of the proposed model regarding primary composition scenario beyond the knee is quite different from most of the prevailing models of the knee and thereby can be discriminated from precise experimental measurement of the primary composition.

  19. Multipotent pancreas progenitors: Inconclusive but pivotal topic.

    Science.gov (United States)

    Jiang, Fang-Xu; Morahan, Grant

    2015-12-26

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  20. Type Ia Progenitor Hunt in Ancient Remnants

    Science.gov (United States)

    Kerzendorf, Wolfgang E.

    2013-01-01

    There is broad agreement that the stars which explode as Type Ia supernovae are white dwarfs. They have accreted material in a binary system until they are near the Chandrasekhar mass and detonate/deflagrate. The two main scenarios for this accretion process are merging with a companion white dwarf (double degenerate scenario), or accretion from a main-sequence to red giant donor (single degenerate scenario). The donor star survives post-explosion and would provide substantial evidence for the single degenerate scenario, if found. Our team is analyzing stars in close proximity to Galactic Type Ia remnants to find surviving donor stars. In my talk I will introduce the different progenitor systems and the expected state for a donor star today. I will outline our search using high resolution spectroscopy and will present updated results.

  1. Progenitor model of cosmic ray knee

    Science.gov (United States)

    Bijay, Biplab; Bhadra, Arunava

    2016-01-01

    The primary energy spectrum of cosmic rays exhibits a knee at about 3 PeV where a change in the spectral index occurs. Despite many efforts, the origin of such a feature in the spectrum is not satisfactorily solved yet. Here it is proposed that the steepening of the spectrum beyond the knee may be a consequence of the mass distribution of the progenitor of the cosmic ray source. The proposed speculative model can account for all the major observed features of cosmic rays without invoking any fine tuning to match flux or spectra at any energy point. The prediction of the proposed model regarding the primary composition scenario beyond the knee is quite different from most of the prevailing models of the knee, and thereby can be discriminated from precise experimental measurement of the primary composition.

  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. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  4. A COMPREHENSIVE PROGENITOR MODEL FOR SNe Ia

    International Nuclear Information System (INIS)

    Although the nature of the progenitor of Type Ia supernovae (SNe Ia) is still unclear, the single-degenerate (SD) channel for the progenitor is currently accepted, in which a carbon-oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion, increases its mass to the Chandrasekhar mass limit, and then explodes as an SN Ia. The companion may be a main sequence or a slightly evolved star (WD + MS), or a red giant star (WD + RG). Incorporating the effect of mass stripping and accretion-disk instability on the evolution of the WD binary, we carried out binary stellar evolution calculations for more than 1600 close WD binaries. As a result, the initial parameter spaces for SNe Ia are presented in an orbital period-secondary mass (log Pi, M i2) plane. We confirmed that in a WD + MS system, the initial companion leading to SNe Ia may have mass from 1 Msun to 5 Msun. The initial WD mass for SNe Ia from WD + MS channel is as low as 0.565 Msun, while the lowest WD mass from the WD + RG channel is 1.0 Msun. Adopting the above results, we studied the birth rate of SNe Ia via a binary population synthesis approach. We found that the Galactic SNe Ia birth rate from SD model is (2.55-2.9) x 10-3 yr-1 (including WD + He star channel), which is slightly smaller than that from observation. If a single starburst is assumed, the distribution of the delay time of SNe Ia from the SD model may be a weak bimodality, where WD + He channel contributes to SNe Ia with delay time shorter than 108 yr and WD + RG channel to those with age longer than 6 Gyr.

  5. Ocean General Circulation Models

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jin-Ho; Ma, Po-Lun

    2012-09-30

    1. Definition of Subject The purpose of this text is to provide an introduction to aspects of oceanic general circulation models (OGCMs), an important component of Climate System or Earth System Model (ESM). The role of the ocean in ESMs is described in Chapter XX (EDITOR: PLEASE FIND THE COUPLED CLIMATE or EARTH SYSTEM MODELING CHAPTERS). The emerging need for understanding the Earth’s climate system and especially projecting its future evolution has encouraged scientists to explore the dynamical, physical, and biogeochemical processes in the ocean. Understanding the role of these processes in the climate system is an interesting and challenging scientific subject. For example, a research question how much extra heat or CO2 generated by anthropogenic activities can be stored in the deep ocean is not only scientifically interesting but also important in projecting future climate of the earth. Thus, OGCMs have been developed and applied to investigate the various oceanic processes and their role in the climate system.

  6. Developmental expression of vascular endothelial growth factor receptor 3 and vascular endothelial growth factor C in forebrain.

    Science.gov (United States)

    Ward, M C; Cunningham, A M

    2015-09-10

    Increased understanding of the neurovascular niche suggests that development of the central nervous system (CNS) and its vasculature is coordinated through shared regulatory factors. These include the vascular endothelial growth factor (VEGF) family, reported to promote neuroproliferation and neuroprotection in addition to angiogenesis via its receptors VEGFR1-3. VEGFR3, a mediator of lymphangiogenesis, is expressed in murine and rat brain from early gestation, has been associated with neural progenitors and neurons (Choi et al., 2010) and oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al., 2011). The early expression pattern of VEGFR3 protein and its cellular associations has not as yet been comprehensively reported. We describe the temporal expression of VEGFR3 protein at a cellular level and its close association with its VEGFC ligand, determined by double-labeling immunohistochemistry in the developing rat brain from embryonic day (E) 13 to postnatal day (P) 23. We found high expression of VEGFR3 in the ventricular zone and along radial glia in early gestation in association with neural stem cells and neuroblasts. Similar expression patterns were seen in the immature olfactory bulb and optic cup. In later development we found less expression by neural progenitors in proliferative regions including the SVZ and dentate gyrus of the hippocampus. In contrast, VEGFR3 expression increased with development in the cortex in neurons and astrocytes, and appeared in the emerging population of oligodendroglial progenitors. High expression in ventricular ependyma, choroid plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was found in association with VEGFR3 throughout development, with highest expression in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3 signaling in neuronal proliferation in early forebrain development

  7. Trypanosoma cruzi: circulating antigens

    Directory of Open Access Journals (Sweden)

    V. Bongertz

    1981-03-01

    Full Text Available Circulating antigens were detected in sera of mice experimentally infected with a high close of Trypanosoma cruzi by reaction with sera from chronically infected mice. The immunodiffusion reaction between homologous acute and chronic sera produced four precipitation lines. By reaction with chronic mouse serum, circulating antingens were detected in sera from heavily infected hamsters, dogs, rabbits and in sera from chagasic patients. A reaction was also found in urine from acutely infected mice and dogs. Trypanosoma cruzi exoantigen was detected in trypanosome culture medium and in the supernatant of infected cell cultures. Attempts to isolate the antigens are described.Antígenos circulantes foram detectados em soros de camundongos infectados experimentalmente com elevadas doses de Trypanosoma cruzi pela reação com soros obtidos de camundongos em fase crônica de infecção. A reação de imunodifusão entre soros homólogos agudo e crônico produziu quatro linhas de precipitação. Por reação com soro crônico de camundongo antígenos circulantes foram detectados em soros de crícetos, cães e coelhos infectados com doses elevadas de Trypanosoma cruzi e em soros de pacientes chagásicos. Uma reação foi também observada com urina de camundongos e cães infectados de forma aguda. Exoantígeno de Trypanosoma cruzi foi detectado em meio de cultura de tripanosomas e em sobrenadantes de culturas de células infectadas. Tentativas de isolamento dos antigenos são descritas.

  8. 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 ...

  9. A continuum model for pressure-flow relationship in human pulmonary circulation.

    Science.gov (United States)

    Huang, Wei; Zhou, Qinlian; Gao, Jian; Yen, R T

    2011-06-01

    A continuum model was introduced to analyze the pressure-flow relationship for steady flow in human pulmonary circulation. The continuum approach was based on the principles of continuum mechanics in conjunction with detailed measurement of vascular geometry, vascular elasticity and blood rheology. The pulmonary arteries and veins were considered as elastic tubes and the "fifth-power law" was used to describe the pressure-flow relationship. For pulmonary capillaries, the "sheet-flow" theory was employed and the pressure-flow relationship was represented by the "fourth-power law". In this paper, the pressure-flow relationship for the whole pulmonary circulation and the longitudinal pressure distribution along the streamlines were studied. Our computed data showed general agreement with the experimental data for the normal subjects and the patients with mitral stenosis and chronic bronchitis in the literature. In conclusion, our continuum model can be used to predict the changes of steady flow in human pulmonary circulation. PMID:21608412

  10. 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.

  11. Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.

    Science.gov (United States)

    Goichberg, Polina

    2016-08-01

    With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential. PMID:27209167

  12. 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.

  13. The Coronary Circulation as a Target of Cardioprotection.

    Science.gov (United States)

    Heusch, Gerd

    2016-05-13

    The atherosclerotic coronary vasculature is not only the culprit but also a victim of myocardial ischemia/reperfusion injury. Manifestations of such injury are increased vascular permeability and edema, endothelial dysfunction and impaired vasomotion, microembolization of atherothrombotic debris, stasis with intravascular cell aggregates, and finally, in its most severe form, capillary destruction with hemorrhage. In animal experiments, local and remote ischemic pre- and postconditioning not only reduce infarct size but also these manifestations of coronary vascular injury, as do drugs which recruit signal transduction steps of conditioning. Clinically, no-reflow is frequently seen after interventional reperfusion, and it carries an adverse prognosis. The translation of cardioprotective interventions to clinical practice has been difficult to date. Only 4 drugs (brain natriuretic peptide, exenatide, metoprolol, and esmolol) stand unchallenged to date in reducing infarct size in patients with reperfused acute myocardial infarction; unfortunately, for these drugs, no information on their impact on the ischemic/reperfused coronary circulation is available. PMID:27174955

  14. Constructal law of vascular trees for facilitation of flow.

    Directory of Open Access Journals (Sweden)

    Mohammad S Razavi

    Full Text Available Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures.

  15. 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

  16. 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.

  17. 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...

  18. 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.

  19. 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 $...

  20. Differentiation of cochlear neural progenitors with SV40 in vitro

    Directory of Open Access Journals (Sweden)

    Yuki Hamajima

    2009-01-01

    Full Text Available Sphere-forming cochlear stem cells/progenitors have recently been isolated from the postnatal mouse organ of Corti. However, self-renewal of the cochlear progenitors remains to be elucidated. Here we demonstrate the renewable cochlear neural progenitors from the postnatal Immortomouse organ of Corti containing a temperature-sensitive SV40 that have the potential to differentiate into hair cell-, neuron-, and supporting cell-like phenotypes under the guidance of sonic hedgehog, epidermal growth factor, retinoic acid, and brain-derived neurotrophic factor, herein termed SERB. This work provides a rationale for using cochlear neural progenitors in possible cell replacement of lost hair cells and neurons in degenerative hearing disorders.

  1. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.

    Science.gov (United States)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir; Jaitin, Diego Adhemar; Kenigsberg, Ephraim; Keren-Shaul, Hadas; Winter, Deborah; Lara-Astiaso, David; Gury, Meital; Weiner, Assaf; David, Eyal; Cohen, Nadav; Lauridsen, Felicia Kathrine Bratt; Haas, Simon; Schlitzer, Andreas; Mildner, Alexander; Ginhoux, Florent; Jung, Steffen; Trumpp, Andreas; Porse, Bo Torben; Tanay, Amos; Amit, Ido

    2015-12-17

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory mechanisms. Here, we comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution. PMID:26627738

  2. 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.

  3. 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...

  4. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  5. Adipose-Derived Stem Cell-Seeded Hydrogels Increase Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds.

    Science.gov (United States)

    Kosaraju, Revanth; Rennert, Robert C; Maan, Zeshaan N; Duscher, Dominik; Barrera, Janos; Whittam, Alexander J; Januszyk, Michael; Rajadas, Jayakumar; Rodrigues, Melanie; Gurtner, Geoffrey C

    2016-02-01

    Adipose-derived mesenchymal stem cells (ASCs) are appealing for cell-based wound therapies because of their accessibility and ease of harvest, but their utility is limited by poor cell survival within the harsh wound microenvironment. In prior work, our laboratory has demonstrated that seeding ASCs within a soft pullulan-collagen hydrogel enhances ASC survival and improves wound healing. To more fully understand the mechanism of this therapy, we examined whether ASC-seeded hydrogels were able to modulate the recruitment and/or functionality of endogenous progenitor cells. Employing a parabiosis model and fluorescence-activated cell sorting analysis, we demonstrate that application of ASC-seeded hydrogels to wounds, when compared with injected ASCs or a noncell control, increased the recruitment of provascular circulating bone marrow-derived mesenchymal progenitor cells (BM-MPCs). BM-MPCs comprised 23.0% of recruited circulating progenitor cells in wounds treated with ASC-seeded hydrogels versus 8.4% and 2.1% in those treated with controls, p functional modulation of BM-MPCs, we demonstrate a statistically significant increase in BM-MPC migration, proliferation, and tubulization when exposed to hydrogel-seeded ASC-conditioned medium versus control ASC-conditioned medium (73.8% vs. 51.4% scratch assay closure; 9.1% vs. 1.4% proliferation rate; 10.2 vs. 5.5 tubules/HPF; p assays). BM-MPC expression of genes related to cell stemness and angiogenesis was also significantly increased following exposure to hydrogel-seeded ASC-conditioned medium (p functionality to effect greater neovascularization. PMID:26871860

  6. Urokinase Receptor Mediates Osteogenic Differentiation of Mesenchymal Stem Cells and Vascular Calcification via the Complement C5a Receptor

    OpenAIRE

    Anaraki, Parnian Kalbasi; Patecki, Margret; Larmann, Jan; Tkachuk, Sergey; Jurk, Kerstin; Haller, Hermann; Theilmeier, Gregor; Dumler, Inna

    2013-01-01

    Vascular calcification is a severe consequence of several pathological processes with a lack of effective therapy. Recent studies suggest that circulating and resident mesenchymal stem cells (MSC) contribute to the osteogenic program of vascular calcification. Molecular mechanisms underlying MSC osteogenic potential and differentiation remain, however, sparsely explored. We investigated a role for the complement receptor C5aR in these processes. We found that expression of C5aR was upregulate...

  7. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

    OpenAIRE

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Benjamin T Suratt; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-01-01

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese m...

  8. Natural Circulation with Boiling

    International Nuclear Information System (INIS)

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed

  9. White Fat Progenitor Cells Reside in the Adipose Vasculature

    OpenAIRE

    Tang, Wei; Zeve, Daniel; Suh, Jae Myoung; Bosnakovski, Darko; Kyba, Michael; Hammer, Robert E.; Tallquist, Michelle D.; Graff, Jonathan M.

    2008-01-01

    White adipose (fat) tissues regulate metabolism, reproduction, and life span. Adipocytes form throughout life, with the most marked expansion of the lineage occurring during the postnatal period. Adipocytes develop in coordination with the vasculature, but the identity and location of white adipocyte progenitor cells in vivo are unknown. We used genetically marked mice to isolate proliferating and renewing adipogenic progenitors. We found that most adipocytes descend from a pool of these prol...

  10. White Fat Progenitors Reside in the Adipose Vasculature*

    OpenAIRE

    Tang, Wei; Zeve, Daniel; Suh, Jae Myoung; Bosnakovski, Darko; Kyba, Michael; Hammer, Robert E.; Tallquist, Michelle D.; Graff, Jonathan M.

    2008-01-01

    White adipose (fat) tissues regulate metabolism, reproduction and lifespan. Adipocytes form throughout life, with the most marked expansion of the lineage occurring during the postnatal period. Adipocytes develop in coordination with the vasculature, but the identity and location of white adipocyte progenitor cells are unknown. We used genetically marked mice to isolate proliferating and renewing adipogenic progenitors. We find that most adipocytes descend from a pool of these proliferating p...

  11. 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.

  12. Endometrial stem/progenitor cells: the first 10 years

    OpenAIRE

    Gargett, Caroline E; Schwab, Kjiana E.; Deane, James A

    2015-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstru...

  13. Sox9 and programming of liver and pancreatic progenitors

    OpenAIRE

    Kawaguchi, Yoshiya

    2013-01-01

    Recent advances in developmental biology have greatly expanded our understanding of progenitor cell programming and the fundamental roles that Sox9 plays in liver and pancreas organogenesis. In the last 2 years, several studies have dissected the behavior of the Sox9+ duct cells in adult organs, but conflicting results have left unanswered the long-standing question of whether physiologically functioning progenitors exist in adult liver and pancreas. On the other hand, increasing evidence sug...

  14. Osteocytes serve as a progenitor cell of osteosarcoma

    OpenAIRE

    Sottnik, Joseph L.; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L.; Keller, Evan T.

    2014-01-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. A...

  15. Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease

    OpenAIRE

    Leeman, Kristen T.; Fillmore, Christine M.; Kim, Carla F.

    2014-01-01

    The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of c...

  16. Endothelial progenitors in sepsis: vox clamantis in deserto?

    OpenAIRE

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the ...

  17. 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

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

    Science.gov (United States)

    Mokhtari, Saloomeh; Colletti, Evan J; Atala, Anthony; Zanjani, Esmail D; Porada, Christopher D; Almeida-Porada, Graça

    2016-06-14

    In utero hematopoietic stem/progenitor cell transplantation (IUHSCT) has only been fully successful in the treatment of congenital immunodeficiency diseases. Using sheep as a large animal model of IUHSCT, we demonstrate that administration of CD146(+)CXCL12(+)VEGFR2(+) or CD146(+)CXCL12(+)VEGFR2(-) cells prior to, or in combination with, hematopoietic stem/progenitor cells (HSC), results in robust CXCL12 production within the fetal marrow environment, and significantly increases the levels of hematopoietic engraftment. While in the fetal recipient, donor-derived HSC were found to reside within the trabecular bone, the increased expression of VEGFR2 in the microvasculature of CD146(+)CXCL12(+)VEGFR2(+) transplanted animals enhanced levels of donor-derived hematopoietic cells in circulation. These studies provide important insights into IUHSCT biology, and demonstrate the feasibility of enhancing HSC engraftment to levels that would likely be therapeutic in many candidate diseases for IUHSCT. PMID:27304918

  19. 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

  20. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

    International Nuclear Information System (INIS)

    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches

  1. 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.

  2. Abdominopelvic vascular injuries.

    Science.gov (United States)

    Sriussadaporn, S

    2000-01-01

    The clinical records of 25 patients with 32 abdominopelvic vascular injuries were reviewed. Sixty per cent of patients sustained blunt trauma and 40 per cent sustained penetrating trauma. Nineteen patients (76%) were in shock on arrival, 2 of them underwent ER thoracotomy when they first arrived in the emergency room. Nine patients (36%) had signs of lower extremity ischemia. The Injury Severity Score (ISS) ranged from 16-50, mean 29 +/- 10.0. Nineteen patients (76%) had 35 associated injuries. Of the 32 injured vessels; 8 were external iliac artery, 5 were renal vein, 4 were abdominal aorta, 3 were common iliac artery, common iliac vein, external iliac vein and inferior vena cava, and 1 was superior mesenteric artery, superior mesenteric vein and median sacral artery. Treatments included: 13 lateral repair, 4 prosthetic grafting, 4 nephrectomy, 3 ligation, 3 reversed saphenous vein grafting, 2 end to end anastomosis, 1 internal iliac artery grafting, 1 intravascular shunt and packing and 1 perihepatic packing. Nine patients (36%) died. High mortality was observed in injuries to the abdominal aorta (75%), inferior vena cava (66.7%), common iliac vein (66.7%) and associated major pelvic fractures (50%). Factors significantly associated with mortality were the presence of shock on arrival, associated injuries and high Injury Severity Score. The author concludes that short prehospital time, effective resuscitation and proper surgical decision making are important for survival in these critically injured patients. PMID:10710864

  3. 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

  4. The Evolution of Relativistic Binary Progenitor Systems

    CERN Document Server

    Francischelli, G J; Brown, G E

    2001-01-01

    Relativistic binary pulsars, such as B1534+12 and B1913+16 are characterized by having close orbits with a binary separation of ~ 3 R_\\sun. The progenitor of such a system is a neutron star, helium star binary. The helium star, with a strong stellar wind, is able to spin up its compact companion via accretion. The neutron star's magnetic field is then lowered to observed values of about 10^{10} Gauss. As the pulsar lifetime is inversely proportional to its magnetic field, the possibility of observing such a system is, thus, enhanced by this type of evolution. We will show that a nascent (Crab-like) pulsar in such a system can, through accretion-braking torques (i.e. the "propeller effect") and wind-induced spin-up rates, reach equilibrium periods that are close to observed values. Such processes occur within the relatively short helium star lifetimes. Additionally, we find that the final outcome of such evolutionary scenarios depends strongly on initial parameters, particularly the initial binary separation a...

  5. 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...

  6. 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.

  7. Possible Progenitor of Special Supernova Type Detected

    Science.gov (United States)

    2008-04-01

    caused by material being pulled off a companion star onto the white dwarf, fusion of this material on the surface of the star should heat the star and produce a strong source of X-radiation prior to the explosion. Once the supernova explosion occurs, the white dwarf is expected to be completely destroyed and then would be undetectable in X-rays. In the merger scenario, the intensity of X-ray emission prior to the explosion is expected to be much weaker. Based on the detection of a fairly strong X-ray source at approximately the position of SN 2007on 4 years before the explosion, Voss and Nelemans conclude that the data support the scenario where matter is pulled off a companion star. The small number of X-ray sources in the field implies that there is only a small chance of an unrelated source being so close by coincidence. Also, the X-ray source has similar properties to those expected for fusion on a white dwarf, unlike most X-ray sources in the sky. However, in follow-up studies, Voss, Nelemans and colleagues Gijs Roelofs (Harvard-Smithsonian Center for Astrophysics, Cambridge, Mass.) and Cees Bassa (McGill University, Canada) used higher-quality optical images to better determine the supernova's position. This work, which is not yet published, shows a small, but significant difference in the measured positions of the supernova and the X-ray source, suggesting the source may not be the progenitor. Follow-up Chandra observations hint that the X-ray object has disappeared, but further observations are needed to finally decide whether the source was the progenitor or not. The team is also applying this new method to other supernovas and has high hopes that they will eventually succeed in identifying the elusive cause of at least some of these explosions. "We're very excited about opening up a new way of studying supernovas, even though we're not sure that we've seen this particular stellar bomb before it exploded," said Gijs Roelofs. "We're very confident that we

  8. 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

  9. 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.

  10. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization.

    Science.gov (United States)

    Sun, Jiayin; Xie, Jun; Kang, Lina; Ferro, Albert; Dong, Li; Xu, Biao

    2016-01-01

    Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg(-1) day(-1)), amlodipine (2.5 mgkg(-1) day(-1)), or vehicle by gavage (n = 20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this. PMID:27243031

  11. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

    Directory of Open Access Journals (Sweden)

    Jiayin Sun

    2016-01-01

    Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

  12. Ultrasound in vascular disease & introduction

    OpenAIRE

    Deane, C; S.Castellani; B. Brkljacic

    2012-01-01

    Il capitolo descrive i prin cipi generali fondamentali delle tecniche per la valutazione ultrasonografica con doppler vascolare The chapter describes the fundamental principles underlying the use of ultrasonographic techniques of vascular doppler

  13. Vascular graft infections with Mycoplasma

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Skov Jensen, J; Prag, J;

    1995-01-01

    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....

  14. The relationships of vascular plants.

    OpenAIRE

    Kenrick, P

    2000-01-01

    Recent phylogenetic research indicates that vascular plants evolved from bryophyte-like ancestors and that this involved extensive modifications to the life cycle. These conclusions are supported by a range of systematic data, including gene sequences, as well as evidence from comparative morphology and the fossil record. Within vascular plants, there is compelling evidence for two major clades, which have been termed lycophytes (clubmosses) and euphyllophytes (seed plants, ferns, horsetails)...

  15. The pathobiology of vascular dementia

    OpenAIRE

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic si...

  16. Zfp423 promotes adipogenic differentiation of bovine stromal vascular cells.

    Directory of Open Access Journals (Sweden)

    Yan Huang

    Full Text Available Intramuscular fat or marbling is critical for the palatability of beef. In mice, very recent studies show that adipocytes and fibroblasts share a common pool of progenitor cells, with Zinc finger protein 423 (Zfp423 as a key initiator of adipogenic differentiation. To evaluate the role of Zfp423 in intramuscular adipogenesis and marbling in beef cattle, we sampled beef muscle for separation of stromal vascular cells. These cells were immortalized with pCI neo-hEST2 and individual clones were selected by G418. A total of 288 clones (3×96 well plates were isolated and induced to adipogenesis. The presence of adipocytes was assessed by Oil-Red-O staining. Three clones with high and low adipogenic potential respectively were selected for further analyses. In addition, fibro/adipogenic progenitor cells were selected using a surface marker, platelet derived growth factor receptor (PDGFR α. The expression of Zfp423 was much higher (307.4±61.9%, P<0.05 in high adipogenic cells, while transforming growth factor (TGF-β was higher (156.1±48.7%, P<0.05 in low adipogenic cells. Following adipogenic differentiation, the expression of peroxisome proliferator-activated receptor γ (PPARγ and CCAAT/enhancer binding protein α (C/EBPα were much higher (239.4±84.1% and 310.7±138.4%, respectively, P<0.05 in high adipogenic cells. Over-expression of Zfp423 in stromal vascular cells and cloned low adipogenic cells dramatically increased their adipogenic differentiation, accompanied with the inhibition of TGF-β expression. Zfp423 knockdown by shRNA in high adipogenic cells largely prevented their adipogenic differentiation. The differential regulation of Zfp423 and TGF-β between low and high adipogenic cells is associated with the DNA methylation in their promoters. In conclusion, data show that Zfp423 is a critical regulator of adipogenesis in stromal vascular cells of bovine muscle, and Zfp423 may provide a molecular target for enhancing intramuscular

  17. 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.

  18. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  19. 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.

  20. Subventricular zone neural progenitors protect striatal neurons from glutamatergic excitotoxicity.

    Science.gov (United States)

    Butti, Erica; Bacigaluppi, Marco; Rossi, Silvia; Cambiaghi, Marco; Bari, Monica; Cebrian Silla, Arantxa; Brambilla, Elena; Musella, Alessandra; De Ceglia, Roberta; Teneud, Luis; De Chiara, Valentina; D'Adamo, Patrizia; Garcia-Verdugo, Jose Manuel; Comi, Giancarlo; Muzio, Luca; Quattrini, Angelo; Leocani, Letizia; Maccarrone, Mauro; Centonze, Diego; Martino, Gianvito

    2012-11-01

    The functional significance of adult neural stem and progenitor cells in hippocampal-dependent learning and memory has been well documented. Although adult neural stem and progenitor cells in the subventricular zone are known to migrate to, maintain and reorganize the olfactory bulb, it is less clear whether they are functionally required for other processes. Using a conditional transgenic mouse model, selective ablation of adult neural stem and progenitor cells in the subventricular zone induced a dramatic increase in morbidity and mortality of central nervous system disorders characterized by excitotoxicity-induced cell death accompanied by reactive inflammation, such as 4-aminopyridine-induced epilepsy and ischaemic stroke. To test the role of subventricular zone adult neural stem and progenitor cells in protecting central nervous system tissue from glutamatergic excitotoxicity, neurophysiological recordings of spontaneous excitatory postsynaptic currents from single medium spiny striatal neurons were measured on acute brain slices. Indeed, lipopolysaccharide-stimulated, but not unstimulated, subventricular zone adult neural stem and progenitor cells reverted the increased frequency and duration of spontaneous excitatory postsynaptic currents by secreting the endocannabinod arachidonoyl ethanolamide, a molecule that regulates glutamatergic tone through type 1 cannabinoid receptor (CB(1)) binding. In vivo restoration of cannabinoid levels, either by administration of the type 1 cannabinoid receptor agonist HU210 or the inhibitor of the principal catabolic enzyme fatty acid amide hydrolase, URB597, completely reverted the increased morbidity and mortality of adult neural stem and progenitor cell-ablated mice suffering from epilepsy and ischaemic stroke. Our results provide the first evidence that adult neural stem and progenitor cells located within the subventricular zone exert an 'innate' homeostatic regulatory role by protecting striatal neurons from glutamate

  1. Vascular Toxicities of Cancer Therapies: The Old and the New - An Evolving Avenue.

    Science.gov (United States)

    Herrmann, Joerg; Yang, Eric H; Iliescu, Cezar A; Cilingiroglu, Mehmet; Charitakis, Konstantinos; Hakeem, Abdul; Toutouzas, Konstantinos; Leesar, Massoud A; Grines, Cindy L; Marmagkiolis, Konstantinos

    2016-03-29

    Since the late 1990s, there has been a steady decline in cancer-related mortality, in part related to the introduction of so-called targeted therapies. Intended to interfere with a specific molecular pathway, these therapies have, paradoxically, led to a number of effects off their intended cancer tissue or molecular targets. The latest examples are tyrosine kinase inhibitors targeting the Philadelphia Chromosome mutation product, which have been associated with progressive atherosclerosis and acute vascular events. In addition, agents designed to interfere with the vascular growth factor signaling pathway have vascular side effects ranging from hypertension to arterial events and cardiomyocyte toxicity. Interestingly, the risk of cardiotoxicity with drugs such as trastuzumab is predicted by preexisting cardiovascular risk factors and disease, posing the question of a vascular component to the pathophysiology. The effect on the coronary circulation has been the leading explanation for the cardiotoxicity of 5-fluorouracil and may be the underlying the mechanism of presentation of apical ballooning syndrome with various chemotherapeutic agents. Classical chemotherapeutic agents such as cisplatin, often used in combination with bleomycin and vinca alkaloids, can lead to vascular events including acute coronary thrombosis and may be associated with an increased long-term cardiovascular risk. This review is intended to provide an update on the evolving spectrum of vascular toxicities with cancer therapeutics, particularly as they pertain to clinical practice, and to the conceptualization of cardiovascular diseases, as well. Vascular toxicity with cancer therapy: the old and the new, an evolving avenue. PMID:27022039

  2. Atmospheric Circulation of Terrestrial Exoplanets

    OpenAIRE

    Showman, Adam P.; Wordsworth, Robin D.; Merlis, Timothy M.; Kaspi, Yohai

    2013-01-01

    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical a...

  3. Flow Cytometric Identification of Fibrocytes in the Human Circulation.

    Science.gov (United States)

    Hu, Xinyuan; DeBiasi, Erin M; Herzog, Erica L

    2015-01-01

    Because the incidence of organ fibrosis increases with age, various fibrosing disorders are projected to account for significant increases in morbidity, mortality, and healthcare costs in the years to come. Treatments for these diseases are scarce and better understanding of the immunopathogenesis of fibrosis and its relationship to aging are sorely needed. One area of interest in this field is the role that fibrocytes might play in the development of tissue remodeling and fibrosis. Fibrocytes are mesenchymal progenitor cells presumed to be of monocyte origin that possess the tissue remodeling properties of tissue resident fibroblasts such as extracellular matrix production and α-SMA-related contractile properties, as well as the immunologic functions typically attributed to macrophages including production of cytokines and chemokines, antigen presentation, regulation of leukocyte trafficking, and modulation of angiogenesis. Fibrocytes could participate in the development of age-related fibrosing disorders through any or all of these functions. This chapter presents methods that have been developed for the study of circulating human fibrocytes. Protocols for the quantification of fibrocytes in the human circulation will be presented along with discussion of the technical challenges that are frequently encountered in this field. It is hoped that this information will facilitate further investigation of the relationship between fibrocytes, aging, and fibrosis, and perhaps uncover new areas of study in these difficult-to-treat and deadly diseases. PMID:26420706

  4. Extracellular vesicles as mediators of vascular inflammation in kidney disease.

    Science.gov (United States)

    Helmke, Alexandra; von Vietinghoff, Sibylle

    2016-03-01

    Vascular inflammation is a common cause of renal impairment and a major cause of morbidity and mortality of patients with kidney disease. Current studies consistently show an increase of extracellular vesicles (EVs) in acute vasculitis and in patients with atherosclerosis. Recent research has elucidated mechanisms that mediate vascular wall leukocyte accumulation and differentiation. This review addresses the role of EVs in this process. Part one of this review addresses functional roles of EVs in renal vasculitis. Most published data address anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and indicate that the number of EVs, mostly of platelet origin, is increased in active disease. EVs generated from neutrophils by activation by ANCA can contribute to vessel damage. While EVs are also elevated in other types of autoimmune vasculitis with renal involvement such as systemic lupus erythematodes, functional consequences beyond intravascular thrombosis remain to be established. In typical hemolytic uremic syndrome secondary to infection with shiga toxin producing Escherichia coli, EV numbers are elevated and contribute to toxin distribution into the vascular wall. Part two addresses mechanisms how EVs modulate vascular inflammation in atherosclerosis, a process that is aggravated in uremia. Elevated numbers of circulating endothelial EVs were associated with atherosclerotic complications in a number of studies in patients with and without kidney disease. Uremic endothelial EVs are defective in induction of vascular relaxation. Neutrophil adhesion and transmigration and intravascular thrombus formation are critically modulated by EVs, a process that is amenable to therapeutic interventions. EVs can enhance monocyte adhesion to the endothelium and modulate macrophage differentiation and cytokine production with major influence on the local inflammatory milieu in the plaque. They significantly influence lipid phagocytosis and antigen presentation by

  5. Cerebellar infarction in vascular territory of arteria cerebelli superior

    Directory of Open Access Journals (Sweden)

    Savić Dejan

    2010-01-01

    Full Text Available Introduction. Cerebellar vascular diseases are focal cerebrovascular diseases in posterior circulation - vertebrobasilar system. The cerebellum is supplied by three main arteries arising from the vertebrobasilar system: arteria cerebelli inferior posterior, arteria cerebelli inferior anterior and arteria cerebelli superior. Cerebelar infarctions are rare but unpredictable disorders. The aim of this study was determination of main risk factors, clinical presentation and prognosis of the cerebellar infarctions in distal vascular territory of the arteria cerebelli superior. Material and methods. We evaluated 60 patients hospitalized after acute cerebellar infarction among other hospitalized patients in five year period. In 18 patients computerized tomography demonstrated infarction in distal vascular territory of the arteria cerebelli superior. All patients underwent clinical and other diagnostic investigations (computerized tomography, electrocardyography and standard blood tests and were questioned by phone after finishing hospital treatment. Results. Cerebellar infarcts in distal vascular territory of arteria cerebeli superior was 30% of all cerebellar infarcts. The most frequent risk factor was hypertension (66. 7%. Symptomatology and clinical signs were heterogenous but the most frequent were instability (77.8%, vertigo (72.2% and vomiting (55.6% followed by ataxia of the limbs (77.8% and the body (61.1%, nystagmus (55.6% and disarthria (33.3% in clinical presentation. All patients had good recovery in hospital and one year afterwards. Discussion. Infarctions in distribution of arteria cerebelli superior are rare and have multiple risk factors and various clinical features in majority of other studies as in this one. Mass effects are present in several studies but none in this one which reflects contraversions present in other published investigations. Conclusion. Cerebellar infarctions in vascular territory of arteria cerebelli superior have

  6. Endogenous circulating sympatholytic factor in orthostatic intolerance

    Science.gov (United States)

    Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.

    2000-01-01

    Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

  7. Obesity in Indian subjects with Vascular Dementia

    OpenAIRE

    CHANDRA, Mina; Anand, Kuljeet Singh Anand

    2015-01-01

    ABSTRACT Background: Obesity is considered a public health challenge in South Asia. Obesity is an independent risk factor in vascular dementia. It also contributes to other risk factors of vascular dementia like hypertension, coronary artery disease, dyslipidaemia and diabetes. As the rate of obesity in Indian subjects with vascular dementia is not known, we decided to assess obesity in subjects with vascular dementia. Methods: Subjects with vascular dementia presenting to Mem...

  8. Impaired DNA replication within progenitor cell pools promotes leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Ganna Bilousova

    2005-12-01

    Full Text Available Impaired cell cycle progression can be paradoxically associated with increased rates of malignancies. Using retroviral transduction of bone marrow progenitors followed by transplantation into mice, we demonstrate that inhibition of hematopoietic progenitor cell proliferation impairs competition, promoting the expansion of progenitors that acquire oncogenic mutations which restore cell cycle progression. Conditions that impair DNA replication dramatically enhance the proliferative advantage provided by the expression of Bcr-Abl or mutant p53, which provide no apparent competitive advantage under conditions of healthy replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in contexts of impaired DNA replication dramatically increases leukemogenesis. Impaired replication within hematopoietic progenitor cell pools can select for oncogenic events and thereby promote leukemia, demonstrating the importance of replicative competence in the prevention of tumorigenesis. The demonstration that replication-impaired, poorly competitive progenitor cell pools can promote tumorigenesis provides a new rationale for links between tumorigenesis and common human conditions of impaired DNA replication such as dietary folate deficiency, chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important for DNA metabolism.

  9. Observational Clues to the Progenitors of Type Ia Supernovae

    Science.gov (United States)

    Maoz, Dan; Mannucci, Filippo; Nelemans, Gijs

    2014-08-01

    Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites—pre- and postexplosion—from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress.

  10. 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; Tuxen, Christian; Fossum, E; Bang, L E; Wiinberg, N; Devereux, R B; Kjeldsen, S E; Hildebrandt, Per; Dige-Petersen, H; Rokkedal, J; Ibsen, H

    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...... losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P...

  11. p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

    Directory of Open Access Journals (Sweden)

    Kyung Hee Chang

    2014-12-01

    Full Text Available In the bone marrow (BM, hematopoietic progenitors (HPs reside in specific anatomical niches near osteoblasts (Obs, macrophages (MΦs, and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling. Consequently, Ob p62-deficient mice lose bone, Ob Ccl4 expression, and HP chemotaxis toward Cxcl12, resulting in egress of short-term hematopoietic stem cells and myeloid progenitors. Finally, Ccl4 expression and myeloid progenitor egress are reversed by deficiency of the p62 PB1-binding partner Nbr1. A functional “MΦ-Ob niche” is required for myeloid progenitor/short-term stem cell retention, in which Ob p62 is required to maintain NF-κB signaling repression, osteogenesis, and BM progenitor retention.

  12. Vascular calcification: Inducers and inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Donghyun, E-mail: dhlee@cau.ac.kr [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)

    2011-09-15

    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  13. Color Doppler in the Assessment of Uteroplacental Circulation Insufficiency

    Directory of Open Access Journals (Sweden)

    Ahmad Soltani Shirazi

    2010-05-01

    Full Text Available Usage of color Doppler ultrasound in the diagnosis of uteroplacental or fetal-placental vascular insufficiency is based on the theory that many of these insufficiencies are due to small vessel disease in the uteroplacental or fetal-placental vasculature which ultimately results in fetal intrauterine growth retardation, increase in prenatal mortality and morbidity and fetal neurological development. "nIn a prospective study on patients who were sus-pected for developing uteroplacental insufficiency, color Doppler ultrasound was done and the results were compared with neonatal weight (one of the most important criteria for IUGR determination which was measured just after delivery."nDirect significant relation was showed to be present between prepartum vascular changes detected in Doppler ultrasound and prognosis of IUGR. "nThree vessel types were assessed in this study:"n1. Umbilical-middle cerebral arteries"n2. Uterine arteries"n3.Venous system (umbilical, ductus venosus, IVC, which is used to assess the compensation process in fetal circulation."nThree Doppler indices of vascular resistance were studied and their abnormalities according to the age of pregnancy were assessed.

  14. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury.

    Science.gov (United States)

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-09-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5(+) (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5(+) cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in

  15. Circulating fibrocytes as predictors of adverse events in unstable angina.

    Science.gov (United States)

    Keeley, Ellen C; Schutt, Robert C; Marinescu, Mark A; Burdick, Marie D; Strieter, Robert M; Mehrad, Borna

    2016-06-01

    Half of the patients who present with unstable angina (UA) develop recurrent symptoms over the subsequent year. Identification of patients destined to develop such adverse events would be clinically valuable, but current tools do not allow for this discrimination. Fibrocytes are bone marrow-derived progenitor cells that co-express markers of leukocytes and fibroblasts and are released into the circulation in the context of tissue injury. We hypothesized that, in patients with UA, the number of circulating fibrocytes predicts subsequent adverse events. We enrolled 55 subjects with UA, 18 with chronic stable angina, and 22 controls and correlated their concentration of circulating fibrocytes to clinical events (recurrent angina, myocardial infarction, revascularization, or death) over the subsequent year. Subjects with UA had a >2-fold higher median concentration of both total and activated fibrocytes compared with subjects with chronic stable angina and controls. In UA subjects, the concentration of total fibrocytes identified those who developed recurrent angina requiring revascularization (time-dependent area under the curve 0.85) and was superior to risk stratification using thrombolysis in myocardial infarction risk score and N-terminal pro B-type natriuretic peptide levels (area under the curve, 0.53 and 0.56, respectively, P fibrocyte level was associated with recurrent angina (hazard ratio, 1.016 per 10,000 cells/mL increase; 95% confidence interval, 1.007-1.024; P fibrocytes are elevated in patients with UA and successfully risk stratify them for adverse clinical outcomes. Fibrocytes may represent a novel biomarker of outcome in this population. PMID:27012475

  16. 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.

  17. 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.

  18. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of rV = 4.26-1.93-0.10+1.39+0.10 h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  19. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael

    2004-08-16

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z {approx} 0.01-0.1 of r{sub V} = 4.26{sub -1.93 -0.10}{sup +1.39 +0.10} h{sup 3} x 10{sup -4} SNe Ia/yr/Mpc{sup 3} from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  20. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  1. A neutron star progenitor for FRBs? Insights from polarisation measurements

    CERN Document Server

    Ravi, Vikram

    2016-01-01

    Fast Radio Bursts (FRBs) are intense, millisecond-duration broadband radio transients, the emission mechanisms of which are not understood. Masui et al. recently presented Green Bank Telescope observations of FRB 110523, which displayed temporal variation of the linear polarisation position angle (PA). This effect is commonly seen in radio pulsars and is attributed to a changing projected magnetic field orientation in the emission region as the star rotates. If a neutron star is the progenitor of this FRB, and the emission mechanism is pulsar-like, we show that the progenitor is either rapidly rotating, or the emission originates from a region of complex magnetic field geometry. The observed PA variation could also be caused by propagation effects within a neutron-star magnetosphere, or by spatially varying magnetic fields if the progenitor lies in a dense, highly magnetised environment. Although we urge caution in generalising results from FRB 110523 to the broader FRB population, our analysis serves as a gu...

  2. CXCR4 expression in prostate cancer progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Dubrovska

    Full Text Available Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+/CD133(+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.

  3. Gravitational Wave Constraints on the Progenitors of Fast Radio Bursts

    CERN Document Server

    Callister, Thomas; Weinstein, Alan

    2016-01-01

    The nature of fast radio bursts (FRBs) remains enigmatic. Highly energetic radio pulses of millisecond duration, fast radio bursts are observed with dispersion measures consistent with an extragalactic source. A variety of models have been proposed to explain their origin. One popular class of theorized FRB progenitor is the coalescence of compact binaries composed of neutron stars and/or black holes. We demonstrate that measurements made by the LIGO and Virgo gravitational wave observatories can be leveraged to severely constrain the validity of FRB binary coalescence models. Existing measurements rule out binary black holes as FRB progenitors, and results from Advanced LIGO's O1 and O2 observing runs will either confirm or strongly rule out binary neutron star and neutron star-black hole progenitors.

  4. Osteocytes serve as a progenitor cell of osteosarcoma.

    Science.gov (United States)

    Sottnik, Joseph L; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L; Keller, Evan T

    2014-08-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, a SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. PMID:24700678

  5. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  6. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale

    2011-01-01

    Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

  7. Vascular Injury in Orthopedic Trauma.

    Science.gov (United States)

    Mavrogenis, Andreas F; Panagopoulos, George N; Kokkalis, Zinon T; Koulouvaris, Panayiotis; Megaloikonomos, Panayiotis D; Igoumenou, Vasilios; Mantas, George; Moulakakis, Konstantinos G; Sfyroeras, George S; Lazaris, Andreas; Soucacos, Panayotis N

    2016-07-01

    Vascular injury in orthopedic trauma is challenging. The risk to life and limb can be high, and clinical signs initially can be subtle. Recognition and management should be a critical skill for every orthopedic surgeon. There are 5 types of vascular injury: intimal injury (flaps, disruptions, or subintimal/intramural hematomas), complete wall defects with pseudoaneurysms or hemorrhage, complete transections with hemorrhage or occlusion, arteriovenous fistulas, and spasm. Intimal defects and subintimal hematomas with possible secondary occlusion are most commonly associated with blunt trauma, whereas wall defects, complete transections, and arteriovenous fistulas usually occur with penetrating trauma. Spasm can occur after either blunt or penetrating trauma to an extremity and is more common in young patients. Clinical presentation of vascular injury may not be straightforward. Physical examination can be misleading or initially unimpressive; a normal pulse examination may be present in 5% to 15% of patients with vascular injury. Detection and treatment of vascular injuries should take place within the context of the overall resuscitation of the patient according to the established principles of the Advanced Trauma Life Support (ATLS) protocols. Advances in the field, made mostly during times of war, have made limb salvage the rule rather than the exception. Teamwork, familiarity with the often subtle signs of vascular injuries, a high index of suspicion, effective communication, appropriate use of imaging modalities, sound knowledge of relevant technique, and sequence of surgical repairs are among the essential factors that will lead to a successful outcome. This article provides a comprehensive literature review on a subject that generates significant controversy and confusion among clinicians involved in the care of trauma patients. [Orthopedics. 2016; 39(4):249-259.]. PMID:27322172

  8. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  9. Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction

    Directory of Open Access Journals (Sweden)

    Obradović Slobodan

    2004-01-01

    Full Text Available Background. Experimental and first clinical studies suggest that the transplantation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial infarction. Aim. This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction. Methods and results. Four male patients (age range 47-68 years with the first extensive anterior, ST elevation, acute myocardial infarction (AMI, were treated by primary angioplasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centrifuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamin stress echocardiography testing and single-photon emission computed tomography (SPECT 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Holter ECG showed only isolated ventricular ectopic beats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction. Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction

  10. Nitric oxide and coronary vascular endothelium adaptations in hypertension

    Directory of Open Access Journals (Sweden)

    Andrew S Levy

    2009-12-01

    Full Text Available Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: This review highlights a number of nitric oxide (NO-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been

  11. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

    Science.gov (United States)

    Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

    2014-03-01

    Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

  12. Risk factors and prevention of vascular complications in polycythemia vera.

    Science.gov (United States)

    Barbui, T; Finazzi, G

    1997-01-01

    Risk factors for vascular complications in polycythemia vera (PV) include laboratory and clinical findings. Among laboratory values, the hematocrit has been clearly associated with thrombosis, particularly in the cerebral circulation. Platelet count is a possible but not yet clearly established predictor of vascular complications. Platelet function tests are of little help in prognostic evaluation because most attempts to correlate these abnormalities with clinical events have been disappointing. Clinical predictors of thrombosis include increasing age and a previous history of vascular events. Identifying risk factors for thrombosis is important to initiate therapy. Phlebotomy is associated with an increased incidence of thrombosis in the first 3 to 5 years, whereas chemotherapy may induce a higher risk of secondary malignancies after 7 to 10 years of follow-up. New cytoreductive drugs virtually devoid of mutagenic risk include interferon-alpha and anagrelide, but their role in reducing thrombotic complications remains to be demonstrated. Antithrombotic drugs, such as aspirin, are frequently used in PV, despite doubts regarding safety and efficacy. Two recent studies from the Gruppo Italiano Studio Policitemia Vera (GISP) assessed the rate of major thrombosis as well as the tolerability of low-dose aspirin in PV patients. These investigations created a favorable scenario for launching a European collaborative clinical trial (ECLAP study) aimed at testing the efficacy of low-dose aspirin in preventing thrombosis and prolonging survival in patients with PV. PMID:9387204

  13. No effect of melatonin to modify surgical-stress response after major vascular surgery: a randomised placebo-controlled trial

    DEFF Research Database (Denmark)

    Kücükakin, B; Wilhelmsen, M; Lykkesfeldt, Jens;

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...

  14. Plant Vascular Biology and Agriculture

    Institute of Scientific and Technical Information of China (English)

    William J.Lucas

    2010-01-01

    @@ The evolution of animal and plant vascular systems played a pivotal role in the advancement from simple to complex organisms,through the provision of a delivery system for the distribution of components essential for both metabolism and growth.Interestingly,although these two vascular systems conform to the same generel rules of fluid dynamics(Murray1926;McCulloh et al.2003),the developmental mechanisms adopted by plants and animals,to generate these long-distance transport systems.have little in common.

  15. Probing Massive Stars Around Gamma-Ray Burst Progenitors

    OpenAIRE

    Lu, Wenbin; Kumar, Pawan; Smoot, George F.

    2015-01-01

    Long Gamma-Ray Bursts (GRBs) are produced by ultra-relativistic jets launched from core collapse of massive stars. Most massive stars form in binaries and/or in star clusters, which means that there may be a significant external photon field (EPF) around the GRB progenitor. We calculate the inverse-Compton scattering of EPF by the hot electrons in the GRB jet. Three possible cases of EPFs are considered: the progenitor is (I) in a massive binary system, (II) surrounded by a Wolf-Rayet-star wi...

  16. Enrichment and terminal differentiation of striated muscle progenitors in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Becher, Ulrich M.; Breitbach, Martin; Sasse, Philipp [Institute of Physiology I, Life and Brain Center, University of Bonn, Bonn (Germany); Garbe, Stephan [Department of Radiology, University of Bonn, Bonn (Germany); Ven, Peter F.M. van der [Institute for Cell Biology, University of Bonn, Bonn (Germany); Fuerst, Dieter O., E-mail: dfuerst@uni-bonn.de [Institute for Cell Biology, University of Bonn, Bonn (Germany); Fleischmann, Bernd K., E-mail: bernd.fleischmann@uni-bonn.de [Institute of Physiology I, Life and Brain Center, University of Bonn, Bonn (Germany)

    2009-10-01

    Enrichment and terminal differentiation of mammalian striated muscle cells is severely hampered by fibroblast overgrowth, de-differentiation and/or lack of functional differentiation. Herein we report a new, reproducible and simple method to enrich and terminally differentiate muscle stem cells and progenitors from mice and humans. We show that a single gamma irradiation of muscle cells induces their massive differentiation into structurally and functionally intact myotubes and cardiomyocytes and that these cells can be kept in culture for many weeks. Similar results are also obtained when treating skeletal muscle-derived stem cells and progenitors with Mitomycin C.

  17. Evolutionary Models for Type Ib/c Supernova Progenitors

    OpenAIRE

    Yoon, Sung-Chul

    2015-01-01

    Type Ib/c supernovae (SNe Ib/c) mark the deaths of hydrogen-deficient massive stars. The evolutionary scenarios for SNe Ib/c progenitors involve many important physical processes including mass loss by winds and its metallicity dependence, stellar rotation, and binary interactions. This makes SNe Ib/c an excellent test bed for stellar evolution theory. We review the main results of evolutionary models for SN Ib/c progenitors available in the literature and their confrontation with recent obse...

  18. Endothelial progenitors in sepsis: vox clamantis in deserto?

    Science.gov (United States)

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the regenerative capacity of mobilized EPCs and the dissociation between the numerical value and clonogenic competence. Attempting to restore the competence to EPCs should be a priority in the future. PMID:21489327

  19. Vascular Function in Alzheimer's Disease and Vascular Dementia.

    Science.gov (United States)

    Tachibana, Hisatsugu; Washida, Kazuo; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2016-08-01

    We investigated vascular functioning in patients with a clinical and radiological diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) and examined a possible relationship between vascular function and cognitive status. Twenty-seven patients with AD, 23 patients with VaD, and 26 healthy control patients underwent measurements of flow-mediated dilation (FMD), ankle-brachial index (ABI), cardioankle vascular index (CAVI), and intima-media thickness (IMT). The FMD was significantly lower in patients with AD or VaD compared to controls. There were no significant differences in ABI, CAVI, or IMT among the 3 groups. A significant correlation was found between Mini-Mental State Examination (MMSE) scores and FMD. Furthermore, a multiple regression analysis revealed that FMD was significantly predicted by MMSE scores. These results suggest that endothelial involvement plays a role in AD pathogenesis, and FMD may be more sensitive than other surrogate methods (ABI, CAVI, and IMT) for detecting early-stage atherosclerosis and/or cognitive decline. PMID:27284205

  20. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter;

    1994-01-01

    vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

  1. Atmospheric Circulation of Terrestrial Exoplanets

    CERN Document Server

    Showman, Adam P; Merlis, Timothy M; Kaspi, Yohai

    2013-01-01

    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical and dynamical conditions, only a small fraction of which have yet been explored in detail. Our approach is to lay out the fundamental dynamical principles governing the atmospheric circulation on terrestrial planets--broadly defined--and show how they can provide a foundation for understanding the atmospheric behavior of these worlds. We first survey basic atmospheric dynamics, including the role of geostrophy, baroclinic instabilities, and jets in the strongly rotating regime (the "extratropics") and the role of the Hadle...

  2. A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity

    Science.gov (United States)

    Pascaud, Juliette; Driancourt, Catherine; Boyer-Di-Ponio, Julie; Uzan, Georges

    2016-01-01

    Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial Progenitor Cells (EPCs) progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs) more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile. PMID:27043207

  3. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  4. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    International Nuclear Information System (INIS)

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

  5. Mutually exclusive signaling signatures define the hepatic and pancreatic progenitor cell lineage divergence

    OpenAIRE

    Rodriguez-Seguel, E.; Mah, N.; Naumann, H.; Pongrac, I.M.; Cerda-Esteban, N.; Fontaine, J.-F.; Wang, Y.; Chen, W; Andrade-Navarro, M A; Spagnoli, F. M.

    2013-01-01

    Understanding how distinct cell types arise from multipotent progenitor cells is a major quest in stem cell biology. The liver and pancreas share many aspects of their early development and possibly originate from a common progenitor. However, how liver and pancreas cells diverge from a common endoderm progenitor population and adopt specific fates remains elusive. Using RNA sequencing (RNA-seq), we defined the molecular identity of liver and pancreas progenitors that were isolated from the m...

  6. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  7. Glucose and acute exercise influence factors secreted by circulating angiogenic cells in vitro

    OpenAIRE

    Witkowski, Sarah; Guhanarayan, Gayatri; Burgess, Rachel

    2016-01-01

    Abstract Circulating angiogenic cells (CAC) influence vascular repair through the secretion of proangiogenic factors and cytokines. While CAC are deficient in patients with diabetes and exercise has a beneficial effect on CACs, the impact of these factors on paracrine secretion from CAC is unknown. We aimed to determine whether the in vitro secretion of selected cytokines and nitric oxide (NO) from CAC is influenced by hyperglycemia and acute exercise. Colony‐forming unit CAC (CFU‐CAC) were c...

  8. Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension

    OpenAIRE

    MacKenzie Ross, Robert V.; Toshner, Mark R.; Soon, Elaine; Naeije, Robert; Pepke-Zaba, Joanna

    2013-01-01

    This study analyzed the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance (Ca) in patients with idiopathic pulmonary arterial hypertension (IPAH) and proximal chronic thromboembolic pulmonary hypertension (CTEPH). It has recently been shown that the time constant of the pulmonary circulation (RC time constant), or PVR × Ca, remains unaltered in various forms and severities of pulmonary hypertension, with the exception of left heart failure. We reasoned...

  9. Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Liana Zucco

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant vascular disorder. Circulating angiogenic cells (CACs play an important role in vascular repair and regeneration. This study was designed to examine the function of CACs derived from patients with HHT. Peripheral blood mononuclear cells (PBMNCs isolated from patients with HHT and age- and gender-matched healthy volunteers were assessed for expression of CD34, CD133 and VEGF receptor 2 by flow cytometry. PBMNCs were cultured to procure early outgrowth CACs. Development of endothelial cell (EC phenotype in CACs was analyzed by fluorescence microscopy. CAC apoptosis was assayed with Annexin V staining, and CAC migration assessed by a modified Boyden chamber assay. mRNA expression of endoglin (ENG, activin receptor-like kinase-1 (ACVLR1 or ALK1 and endothelial nitric oxide synthase (eNOS in CACs was measured by real time RT-PCR. The percentage of CD34+ cells in PBMNCs from HHT patients was significantly higher than in PBMNCs of healthy controls. CACs derived from patients with HHT not only showed a significant reduction in EC-selective surface markers following 7-day culture, but also a significant increase in the rate of basal apoptosis and blunted migration in response to vascular endothelial growth factor and stromal cell-derived factor-1. CACs from HHT patients expressed significantly lower levels of ENG, ALK1 and eNOS mRNAs. In conclusion, CACs from patients with HHT exhibited various functional impairments, suggesting a reduced regenerative capacity of CACs to repair the vascular lesions seen in HHT patients.

  10. File list: Unc.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.50.AllAg.Multipotent_otic_progenitor mm9 Unclassified Others Multipotent ot...ic progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  11. File list: Oth.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.20.AllAg.Multipotent_otic_progenitor mm9 TFs and others Others Multipotent ...otic progenitor SRX736459,SRX736458,SRX736460,SRX736461 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  12. File list: Oth.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.10.AllAg.Multipotent_otic_progenitor mm9 TFs and others Others Multipotent ...otic progenitor SRX736459,SRX736458,SRX736460,SRX736461 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  13. File list: His.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.20.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  14. File list: Pol.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.05.AllAg.Multipotent_otic_progenitor mm9 RNA polymerase Others Multipotent ...otic progenitor SRX736456,SRX736457 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  15. File list: His.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.10.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  16. File list: Pol.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.20.AllAg.Multipotent_otic_progenitor mm9 RNA polymerase Others Multipotent ...otic progenitor SRX736457,SRX736456 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  17. File list: Unc.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.20.AllAg.Multipotent_otic_progenitor mm9 Unclassified Others Multipotent ot...ic progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  18. File list: His.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  19. File list: DNS.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.20.AllAg.Multipotent_otic_progenitor mm9 DNase-seq Others Multipotent otic ...progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  20. File list: DNS.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

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