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Sample records for reduce ventilator-induced vascular

  1. Protective Ventilation of Preterm Lambs Exposed to Acute Chorioamnionitis Does Not Reduce Ventilation-Induced Lung or Brain Injury

    PubMed Central

    Barton, Samantha K.; Moss, Timothy J. M.; Hooper, Stuart B.; Crossley, Kelly J.; Gill, Andrew W.; Kluckow, Martin; Zahra, Valerie; Wong, Flora Y.; Pichler, Gerhard; Galinsky, Robert; Miller, Suzanne L.

    2014-01-01

    Background The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. Methods Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. Results LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. Conclusions Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor

  2. Neutrophil elastase inhibitor reduces ventilation-induced lung injury via nuclear factor-κB and NF-κB repressing factor in mice.

    PubMed

    Li, Li-Fu; Lai, Yi-Ting; Chang, Chih-Hao; Lin, Meng-Chih; Liu, Yung-Yang; Kao, Kuo-Chin; Tsai, Ying-Huang

    2014-04-11

    Mechanical ventilation used in patients with acute lung injury can damage pulmonary epithelial cells through production of inflammatory cytokines, oxygen radicals, and neutrophil infiltration, termed ventilator-induced lung injury. Neutrophil elastase, nuclear factor-κB (NF-κB), and NF-κB repressing factor (NRF) have previously been shown to participate in the regulation of macrophage inflammatory protein-2 (MIP-2) during airway inflammation. However, the mechanisms regulating interactions among mechanical ventilation, neutrophil influx, and NF-κB/NRF remain unclear. Thus, we hypothesized that neutrophil elastase inhibitor attenuated ventilation-induced neutrophil recruitment and MIP-2 production through inhibition of the NF-κB/NRF pathway. Male C57BL/6 mice were exposed to low-tidal-volume (6 mL/kg) or high-tidal-volume (30 mL/kg) mechanical ventilation using room air with or without 2 µg/g NF-κB inhibitor SN50 or 6 µg/g NRF short interfering RNA or 100 µg/g neutrophil elastase inhibitor administration. Nonventilated mice served as a control group. Evan blue dye, lung wet-to-dry weight ratio, free radicals, myeloperoxidase, histopathologic grading of lung tissue, inflammatory cytokines, Western blot of NF-κB and NRF, and gene expression of NRF were measured to establish the extent of lung injury. Neutrophil elastase inhibitor ameliorated high-tidal-volume ventilation-induced lung injury, neutrophil influx, production of MIP-2 and malondialdehyde, activation of NF-κB and NRF, apoptotic epithelial cell death, and disruption of bronchial microstructure in mice. Mechanical stretch-augmented acute lung injury was also attenuated through pharmacological inhibition of NF-κB activity by SN50 and NRF expression by NRF short interfering RNA. Our data suggest that neutrophil elastase inhibitor attenuates high-tidal-volume mechanical ventilation-induced neutrophil influx, oxidative stress, and production of MIP-2, at least partly, through inhibition of

  3. Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury

    PubMed Central

    Liu, Dejie; Yan, Zhibo; Minshall, Richard D.; Schwartz, David E.; Chen, Yuguo

    2012-01-01

    Lung inflammatory responses in the absence of infection are considered to be one of primary mechanisms of ventilator-induced lung injury. Here, we determined the role of calpain in the pathogenesis of lung inflammation attributable to mechanical ventilation. Male C57BL/6J mice were subjected to high (28 ml/kg) tidal volume ventilation for 2 h in the absence and presence of calpain inhibitor I (10 mg/kg). To address the isoform-specific functions of calpain 1 and calpain 2 during mechanical ventilation, we utilized a liposome-based delivery system to introduce small interfering RNAs targeting each isoform in pulmonary vasculature in vivo. Mechanical ventilation with high tidal volume induced rapid (within minutes) and persistent calpain activation and lung inflammation as evidenced by neutrophil recruitment, production of TNF-α and IL-6, pulmonary vascular hyperpermeability, and lung edema formation. Pharmaceutical calpain inhibition significantly attenuated these inflammatory responses caused by lung hyperinflation. Depletion of calpain 1 or calpain 2 had a protective effect against ventilator-induced lung inflammatory responses. Inhibition of calpain activity by means of siRNA silencing or pharmacological inhibition also reduced endothelial nitric oxide (NO) synthase (NOS-3)-mediated NO production and subsequent ICAM-1 phosphorylation following high tidal volume ventilation. These results suggest that calpain activation mediates early lung inflammation during ventilator-induced lung injury via NOS-3/NO-dependent ICAM-1 phosphorylation and neutrophil recruitment. Inhibition of calpain activation may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. PMID:22140070

  4. Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

    SciTech Connect

    Huang, Chien-Sheng; Kawamura, Tomohiro; Peng, Ximei; Tochigi, Naobumi; Shigemura, Norihisa; Billiar, Timothy R.; Nakao, Atsunori; Toyoda, Yoshiya

    2011-05-06

    Highlights: {yields} Hydrogen is a regulatory molecule with antiinflammatory and antiapoptotic protective effects. {yields} There is very limited information on the pathways regulated in vivo by the hydrogen. {yields} Antiapoptotic abilities of hydrogen were explained by upregulation of the antiapoptotic gene. {yields} NF{kappa}B activation during hydrogen treatment was correlated with elevated antiapoptotic protein. {yields} NF{kappa}B activation associated with increase Bcl-2 may contribute to cytoprotection of hydrogen. -- Abstract: We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NF{kappa}B) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NF{kappa}B activation, as indicated by NF{kappa}B DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NF{kappa}B DNA binding after 1 h of ventilation and decreased NF{kappa}B DNA binding after 2 h of ventilation, as compared with controls. The early activation of NF{kappa}B during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NF{kappa}B activation using SN50 reversed these protective effects. NF{kappa}B activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the

  5. Metformin attenuates ventilator-induced lung injury

    PubMed Central

    2012-01-01

    Introduction Diabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury. Methods Twenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH2O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH2O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF. Results High-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation. Conclusions Pretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model. PMID:22827994

  6. Measures to reduce unplanned readmissions after vascular surgery.

    PubMed

    Eun, John C; Nehler, Mark R; Black, James H; Glebova, Natalia O

    2015-06-01

    Hospital readmissions are increasingly utilized as a measure of health care quality. Unplanned readmissions in surgical patients are viewed as a marker of poor care quality, and are associated with significant expense both to the health care system and to the patient. Interventions aimed at reducing readmissions have been the focus of several prospective randomized trials addressing medical conditions like congestive heart failure, but few data exist on efforts to reduce readmissions in surgical patients. Vascular surgery patients have been found to be at a particularly high risk for readmission, and a number of groups have reported on the risk factors for readmission in these patients. However, measures to reduce unplanned readmissions after vascular surgery have not be thoroughly investigated. Here, we summarize the existing data on risk factors for readmission in vascular surgery patients, review interventional studies in medical patients aimed at reducing readmissions, and suggest interventions that may be helpful in reducing readmissions in vascular patients. Further investigative work is needed to ascertain practical approaches to reducing unplanned readmissions in vascular surgery patients and thus improve the quality of care they receive.

  7. VEGF Production by Ly6C+high Monocytes Contributes to Ventilator-Induced Lung Injury

    PubMed Central

    Lin, Chin-Kuo; Li, Jhy-Ming; Chen, Mei-Hsin; Tsai, Mei-Ling; Chang, Chih-Ching

    2016-01-01

    Background Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilator-induced lung injury (VILI). Ly6C+high monocytes are involved in the pathogenesis of VILI. In this study, we investigated whether pulmonary infiltrated Ly6C+high monocytes produce vascular endothelial growth factor (VEGF) and contribute to VILI. Methods A clinically relevant two-hit mouse model of VILI, with intravenous lipopolysaccharide (LPS, 20 ng/mouse) immediately before high tidal volume (HTV, 20 mL/kg) ventilation (LPS+HTV), was established. Blood gas and respiratory mechanics were measured to ensure the development of VILI. Flow cytometry and histopathological analyses revealed pulmonary infiltration of leukocytes subsets. Clodronate liposomes were intravenously injected to deplete pulmonary monocytes. In vitro endothelial cell permeability assay with sorted Ly6C+high monocytes condition media assessed the role of Ly6C+high monocytes in vascular permeability. Results LPS+HTV significantly increased total proteins, TNF-α, IL-6, vascular endothelial growth factor (VEGF) and mononuclear cells in the bronchoalveolar lavage fluid (BALF). Pulmonary Ly6C+high monocytes (SSClowCD11b+F4/80+Ly6C+high), but not Ly6C+low monocytes (SSClowCD11b+F4/80+Ly6C+low), were significantly elevated starting at 4 hr. Clodronate liposomes were able to significantly reduce pulmonary Ly6C+high monocytes, and VEGF and total protein in BALF, and restore PaO2/FiO2. There was a strong correlation between pulmonary Ly6C+high monocytes and BALF VEGF (R2 = 0.8791, p<0.001). Moreover, sorted Ly6C+high monocytes were able to produce VEGF, resulting in an increased permeability of endothelial cell monolayer in an in vitro endothelial cell permeability assay. Conclusion VEGF produced by pulmonary infiltrated Ly6C+high monocytes regulates vasculature permeability in a two-hit model of HTV-induced lung

  8. Ventilator-induced lung injury in preterm infants

    PubMed Central

    Carvalho, Clarissa Gutierrez; Silveira, Rita C; Procianoy, Renato Soibelmann

    2013-01-01

    In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants. PMID:24553514

  9. How data can help reduce vascular access events.

    PubMed

    Swails-Climer, Mary

    2012-11-01

    Thrombosis is the leading cause of access dysfunction and is expensive to treat. In 2011, only 10 AV access capable patients in our center were placed on a bridge catheter because of our ability to assess health and proactively use angioplasty to keep it open. Surveillance also helped us follow the progression of new fistula maturation and helped us decide on early intervention to prevent total, access failure. The Sparrow Center documented successful results with the selection of a new surveillance system that dramatically improved the quality of patient care and financial viability of the center. For dialysis center staffs looking for ways to operate more efficiently and at the same time reduce the incidence of vascular access complications caused by thrombosis, a data-driven surveillance device along with clinical monitoring protocols seems to provide a cost effective approach to addressing this critical area of patient care.

  10. Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs.

    PubMed

    Allison, Beth J; Hooper, Stuart B; Coia, Elise; Zahra, Valerie A; Jenkin, Graham; Malhotra, Atul; Sehgal, Arvind; Kluckow, Martin; Gill, Andrew W; Sozo, Foula; Miller, Suzanne L; Polglase, Graeme R

    2016-02-01

    Intrauterine growth restriction (IUGR) and preterm birth are frequent comorbidities and, combined, increase the risk of adverse respiratory outcomes compared with that in appropriately grown (AG) infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared with AG infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements, and/or increased ventilation-induced lung injury. IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury, and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. IUGR preterm lambs weighed 30% less than AG preterm lambs, with increased brain-to-body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared with AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth and had significant, but similar, increases in proinflammatory cytokine expression, lung injury markers, gene expression, and surfactant phosphatidylcholine species compared with unventilated controls. IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.

  11. Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs.

    PubMed

    Allison, Beth J; Hooper, Stuart B; Coia, Elise; Zahra, Valerie A; Jenkin, Graham; Malhotra, Atul; Sehgal, Arvind; Kluckow, Martin; Gill, Andrew W; Sozo, Foula; Miller, Suzanne L; Polglase, Graeme R

    2016-02-01

    Intrauterine growth restriction (IUGR) and preterm birth are frequent comorbidities and, combined, increase the risk of adverse respiratory outcomes compared with that in appropriately grown (AG) infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared with AG infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements, and/or increased ventilation-induced lung injury. IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury, and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. IUGR preterm lambs weighed 30% less than AG preterm lambs, with increased brain-to-body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared with AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth and had significant, but similar, increases in proinflammatory cytokine expression, lung injury markers, gene expression, and surfactant phosphatidylcholine species compared with unventilated controls. IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation. PMID:26608532

  12. Globular adiponectin reduces vascular calcification via inhibition of ER-stress-mediated smooth muscle cell apoptosis

    PubMed Central

    Lu, Yan; Bian, Yunfei; Wang, Yueru; Bai, Rui; Wang, Jiapu; Xiao, Chuanshi

    2015-01-01

    Objective: This study aims to explore the mechanism of globular adiponectin inhibiting vascular calcification. Methods: We established drug-induced rat vascular calcification model, globular adiponectin was given to observe the effect of globular Adiponectin on the degree of calcification. The markers of vascular calcification and apoptosis were also investigated. Meanwhile, the in vitro effect of globular Adiponectin on vascular calcification was also evaluated using primary cultured rat vascular smooth muscle cells. Results: We found that globular adiponectin could inhibit drug-induced rat vascular calcification significantly in vivo. The apoptosis of vascular smooth muscle cells was also reduced. The possible mechanism could be the down-regulation of endoplasmic reticulum stress by globular adiponectin. Experiments in primary cultured vascular smooth muscle cells also confirmed that globular adiponectin could reduce cell apoptosis to suppress vascular calcification via inhibition of endoplasmic reticulum stress. Conclusions: This study confirmed that globular adiponectin could suppress vascular calcification; one of the mechanisms could be inhibition of endoplasmic reticulum stress to reduce cell apoptosis. It could provide an effective method in the therapy of vascular calcification-associated diseases. PMID:26045760

  13. Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-κB-mediated inflammation.

    PubMed

    Ma, Hongzhong; Feng, Xiaoli; Ding, Suchun

    2015-12-15

    Hesperetin, a major bioflavonoid in sweet oranges and lemons, has been reported to have anti-inflammatory properties. However, the effect of hesperetin on ventilator-induced acute lung injury has not been studied. In present study, we investigated the protective effect of hesperetin on ventilator-induced acute lung injury in rats. Rats were orally administered hesperetin (10, 20, or 40mg/kg) two hour before acute lung injury was induced by mechanical ventilation. Rats were then randomly divided into six groups: the lung protective ventilation group (n=20, LV group), injurious ventilation group (n=20, HV group), vehicle-treated injurious ventilation group (n=20, LV+vehicle group), hesperetin (10mg/kg)-treated acute lung injury group (n=20, HV+Hsp (10mg)), hesperetin (20mg/kg)-treated acute lung injury group (n=20, HV+Hsp (20mg)), and hesperetin (40mg/kg)-treated acute lung injury group (n=20, HV+Hsp (40mg)). The lung tissues and bronchoalveolar lavage fluid were isolated for subsequent measurements. Treatment with hesperetin dramatically improved the histology of lung tissue, and reduced the wet/dry ratio, myeloperoxidase activity, protein concentration, and production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and MIP-2 in the bronchoalveolar lavage fluid of rats with ventilator-induced acute lung injury. Additionally, our study indicated that this protective effect of hesperetin results from its ability to increase the expression of peroxisome proliferator-activated receptor (PPAR)-γ and inhibit the activation of the nuclear factor (NF)-κB pathway. These results suggest that hesperetin may be a potential novel therapeutic candidate for protection against ventilator-induced acute lung injury.

  14. Intermedin Stabilized Endothelial Barrier Function and Attenuated Ventilator-induced Lung Injury in Mice

    PubMed Central

    Müller-Redetzky, Holger Christian; Kummer, Wolfgang; Pfeil, Uwe; Hellwig, Katharina; Will, Daniel; Paddenberg, Renate; Tabeling, Christoph; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

    2012-01-01

    Background Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methodology/Principal Findings Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. Conclusions/Significance IMD may possibly provide a new approach to attenuate VILI. PMID:22563471

  15. The physical basis of ventilator-induced lung injury

    PubMed Central

    Plataki, Maria; Hubmayr, Rolf D

    2010-01-01

    Although mechanical ventilation (MV) is a life-saving intervention for patients with acute respiratory distress syndrome (ARDS), it can aggravate or cause lung injury, known as ventilator-induced lung injury (VILI). The biophysical characteristics of heterogeneously injured ARDS lungs increase the parenchymal stress associated with breathing, which is further aggravated by MV. Cells, in particular those lining the capillaries, airways and alveoli, transform this strain into chemical signals (mechanotransduction). The interaction of reparative and injurious mechanotransductive pathways leads to VILI. Several attempts have been made to identify clinical surrogate measures of lung stress/strain (e.g., density changes in chest computed tomography, lower and upper inflection points of the pressure–volume curve, plateau pressure and inflammatory cytokine levels) that could be used to titrate MV. However, uncertainty about the topographical distribution of stress relative to that of the susceptibility of the cells and tissues to injury makes the existence of a single ‘global’ stress/strain injury threshold doubtful. PMID:20524920

  16. Vascular design for reducing hot spots and stresses

    NASA Astrophysics Data System (ADS)

    Rocha, L. A. O.; Lorente, S.; Bejan, A.

    2014-05-01

    This paper is a proposal to embed tree-shaped vasculatures in a wall designed such that the wall withstands without excessive hot spots and peak stresses the intense heating and pressure that impinge on it. The vasculature is a quilt of square-shaped panels, each panel having a tree vasculature that connects the center with the perimeter. The vascular designs for volumetric cooling can be complemented by the shaping and distributing of channels for maximum strength and thermal performance at the same time. Numerical simulations of heat flow and thermal stresses in three directions show that it is possible to determine the optimal geometric features of configurations with radial channels and trees with radial and one level of bifurcations. The global performance is evaluated in terms of the overall thermal resistance and peak von Mises stresses. The dendritic design is superior under the studied thermal condition.

  17. Pre-Treatment with Allopurinol or Uricase Attenuates Barrier Dysfunction but Not Inflammation during Murine Ventilator-Induced Lung Injury

    PubMed Central

    Kuipers, Maria T.; Aslami, Hamid; Vlaar, Alexander P. J.; Juffermans, Nicole P.; Tuip-de Boer, Anita M.; Hegeman, Maria A.; Jongsma, Geartsje; Roelofs, Joris J. T. H.; van der Poll, Tom; Schultz, Marcus J.; Wieland, Catharina W.

    2012-01-01

    Introduction Uric acid released from injured tissue is considered a major endogenous danger signal and local instillation of uric acid crystals induces acute lung inflammation via activation of the NLRP3 inflammasome. Ventilator-induced lung injury (VILI) is mediated by the NLRP3 inflammasome and increased uric acid levels in lung lavage fluid are reported. We studied levels in human lung injury and the contribution of uric acid in experimental VILI. Methods Uric acid levels in lung lavage fluid of patients with acute lung injury (ALI) were determined. In a different cohort of cardiac surgery patients, uric acid levels were correlated with pulmonary leakage index. In a mouse model of VILI the effect of allopurinol (inhibits uric acid synthesis) and uricase (degrades uric acid) pre-treatment on neutrophil influx, up-regulation of adhesion molecules, pulmonary and systemic cytokine levels, lung pathology, and regulation of receptors involved in the recognition of uric acid was studied. In addition, total protein and immunoglobulin M in lung lavage fluid and pulmonary wet/dry ratios were measured as markers of alveolar barrier dysfunction. Results Uric acid levels increased in ALI patients. In cardiac surgery patients, elevated levels correlated significantly with the pulmonary leakage index. Allopurinol or uricase treatment did not reduce ventilator-induced inflammation, IκB-α degradation, or up-regulation of NLRP3, Toll-like receptor 2, and Toll-like receptor 4 gene expression in mice. Alveolar barrier dysfunction was attenuated which was most pronounced in mice pre-treated with allopurinol: both treatment strategies reduced wet/dry ratio, allopurinol also lowered total protein and immunoglobulin M levels. Conclusions Local uric acid levels increase in patients with ALI. In mice, allopurinol and uricase attenuate ventilator-induced alveolar barrier dysfunction. PMID:23226314

  18. Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

    PubMed Central

    Jones, Heather D.; Yoo, Jeena; Crother, Timothy R.; Kyme, Pierre; Ben-Shlomo, Anat; Khalafi, Ramtin; Tseng, Ching W.; Parks, William C.; Arditi, Moshe

    2015-01-01

    Background Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3) directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury. Methods We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε. Results Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice. Conclusions Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but

  19. Cervical spinal cord injury exacerbates ventilator-induced diaphragm dysfunction.

    PubMed

    Smuder, Ashley J; Gonzalez-Rothi, Elisa J; Kwon, Oh Sung; Morton, Aaron B; Sollanek, Kurt J; Powers, Scott K; Fuller, David D

    2016-01-15

    Cervical spinal cord injury (SCI) can dramatically impair diaphragm muscle function and often necessitates mechanical ventilation (MV) to maintain adequate pulmonary gas exchange. MV is a life-saving intervention. However, prolonged MV results in atrophy and impaired function of the diaphragm. Since cervical SCI can also trigger diaphragm atrophy, it may create preconditions that exacerbate ventilator-induced diaphragm dysfunction (VIDD). Currently, no drug therapy or clinical standard of care exists to prevent or minimize diaphragm dysfunction following SCI. Therefore, we first tested the hypothesis that initiating MV acutely after cervical SCI will exacerbate VIDD and enhance proteolytic activation in the diaphragm to a greater extent than either condition alone. Rats underwent controlled MV for 12 h following acute (∼24 h) cervical spinal hemisection injury at C2 (SCI). Diaphragm tissue was then harvested for comprehensive functional and molecular analyses. Second, we determined if antioxidant therapy could mitigate MV-induced diaphragm dysfunction after cervical SCI. In these experiments, SCI rats received antioxidant (Trolox, a vitamin E analog) or saline treatment prior to initiating MV. Our results demonstrate that compared with either condition alone, the combination of SCI and MV resulted in increased diaphragm atrophy, contractile dysfunction, and expression of atrophy-related genes, including MuRF1. Importantly, administration of the antioxidant Trolox attenuated proteolytic activation, fiber atrophy, and contractile dysfunction in the diaphragms of SCI + MV animals. These findings provide evidence that cervical SCI greatly exacerbates VIDD, but antioxidant therapy with Trolox can preserve diaphragm contractile function following acute SCI. PMID:26472866

  20. Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy

    PubMed Central

    2012-01-01

    Background Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy. Methods Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS). Results Both the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group. Conclusion Inhibition of nNOS improved gas exchange, but did not

  1. Suppressive oligonucleotides inhibit inflammation in a murine model of mechanical ventilator induced lung injury

    PubMed Central

    Scheiermann, Julia

    2016-01-01

    Background Mechanical ventilation (MV) is commonly used to improve blood oxygenation in critically ill patients and for general anesthesia. Yet the cyclic mechanical stress induced at even moderate ventilation volume settings [tidal volume (Vt) <10 mL/kg] can injure the lungs and induce an inflammatory response. This work explores the effect of treatment with suppressive oligonucleotides (Sup ODN) in a mouse model of ventilator-induced lung injury (VILI). Methods Balb/cJ mice were mechanically ventilated for 4 h using clinically relevant Vt and a positive end-expiratory pressure of 3 cmH2O under 2–3% isoflurane anesthesia. Lung tissue and bronchoalveolar lavage fluid were collected to assess lung inflammation and lung function was monitored using a FlexiVent®. Results MV induced significant pulmonary inflammation characterized by the influx and activation of CD11c+/F4/80+ macrophages and CD11b+/Ly6G+ polymorphonuclear cells into the lung and bronchoalveolar lavage fluid. The concurrent administration of Sup ODN attenuated pulmonary inflammation as evidenced by reduced cellular influx and production of inflammatory cytokines. Oligonucleotide treatment did not worsen lung function as measured by static compliance or resistance. Conclusions Treatment with Sup ODN reduces the lung injury induced by MV in mice. PMID:27746995

  2. Recruitment Maneuver Does not Increase the Risk of Ventilator Induced Lung Injury

    PubMed Central

    Akıncı, İbrahim Özkan; Atalan, Korkut; Tuğrul, Simru; Özcan, Perihan Ergin; Yılmazbayhan, Dilek; Kıran, Bayram; Basel, Ahmet; Telci, Lutfi; Çakar, Nahit

    2013-01-01

    Background: Mechanical ventilation (MV) may induce lung injury. Aims: To assess and evaluate the role of different mechanical ventilation strategies on ventilator-induced lung injury (VILI) in comparison to a strategy which includes recruitment manoeuvre (RM). Study design: Randomized animal experiment. Methods: Thirty male Sprague-Dawley rats were anaesthetised, tracheostomised and divided into 5 groups randomly according to driving pressures; these were mechanically ventilated with following peak alveolar opening (Pao) and positive end-expiratory pressures (PEEP) for 1 hour: Group 15-0: 15 cmH2O Pao and 0 cmH2O PEEP; Group 30-10: 30 cmH2O Pao and 10 cmH2O PEEP; Group 30-5: 30 cmH2O Pao and 5 cmH2O PEEP; Group 30-5&RM: 30 cmH2O Pao and 5 cmH2O PEEP with additional 45 cmH2O CPAP for 30 seconds in every 15 minutes; Group 45-0: 45 cmH2O Pao and 0 cmH2O PEEP Before rats were sacrificed, blood samples were obtained for the evaluation of cytokine and chemokine levels; then, the lungs were subsequently processed for morphologic evaluation. Results: Oxygenation results were similar in all groups; however, the groups were lined as follows according to the increasing severity of morphometric evaluation parameters: Group 15-0: (0±0.009) < Group 30-10: (0±0.14) < Group 30-5&RM: (1±0.12) < Group 30-5: (1±0.16) < Group 45-0: (2±0.16). Besides, inflammatory responses were the lowest in 30-5&RM group compared to all other groups. TNF-α, IL-1β, IL-6, MCP-1 levels were significantly different between group 30-5&RM and group 15-0 vs. group 45-0 in each group. Conclusion: RM with low PEEP reduces the risk of ventilator-induced lung injury with a lower release of systemic inflammatory mediators in response to mechanical ventilation. PMID:25207105

  3. The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice.

    PubMed

    Koga, Mitsuhisa; Engberding, Niels; Dikalova, Anna E; Chang, Kyung Hwa; Seidel-Rogol, Bonnie; Long, James S; Lassègue, Bernard; Jo, Hanjoong; Griendling, Kathy K

    2013-09-01

    Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease. PMID:23812391

  4. The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction.

    PubMed

    Salah, Heba; Li, Meishan; Cacciani, Nicola; Gastaldello, Stefano; Ogilvie, Hannah; Akkad, Hazem; Namuduri, Arvind Venkat; Morbidoni, Valeria; Artemenko, Konstantin A; Balogh, Gabor; Martinez-Redondo, Vicente; Jannig, Paulo; Hedström, Yvette; Dworkin, Barry; Bergquist, Jonas; Ruas, Jorge; Vigh, Laszlo; Salviati, Leonardo; Larsson, Lars

    2016-08-01

    Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences for individual patients' quality of life and for the health care system, but specific treatment strategies are still lacking. We used an experimental intensive care unit (ICU) model, allowing time-resolved studies of diaphragm structure and function in response to long-term mechanical ventilation and the effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The marked loss of diaphragm muscle fiber function in response to mechanical ventilation was caused by posttranslational modifications (PTMs) of myosin. In a rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber function (by about 100%), although it did not reverse diaphragm atrophy. The treatment also provided protection from myosin PTMs associated with HSP72 induction and PARP-1 inhibition, resulting in improvement of mitochondrial function and content. Thus, BGP-15 may offer an intervention strategy for reducing VIDD in mechanically ventilated ICU patients. PMID:27488897

  5. The protective effects of glutamine in a rat model of ventilator-induced lung injury

    PubMed Central

    Chen, Chin-Ming; Cheng, Kuo-Chen; Li, Chien-Feng

    2014-01-01

    Background The mortality rate of patients with acute respiratory distress syndrome (ARDS) is still high despite the use of protective ventilatory strategies. We sought to examine the pharmacological effects of glutamine (GLN) in a two-hit model of endotoxin-induced inflammation followed by ventilator-induced lung injury (VILI). We hypothesized that the administration of GLN ameliorates the VILI. Methods Sprague-Dawley rats were anesthetized and given lipopolysaccharide (LPS) intratracheally as a first hit to induce lung inflammation, followed 24 h later by a second hit of mechanical ventilation (MV) with either low tidal volume (6 mL/kg) with 5 cmH2O of positive end-expiratory pressure (PEEP) or high tidal volume (22 mL/kg) with zero PEEP for 4 h. GLN or lactated Ringer’s solution as the placebo was administered intravenously 15 min prior to MV. Results In the LPS-challenged rats ventilated with high tidal volume, the treatment with GLN improved lung injury indices, lung mechanics and cytokine responses compared with the placebo group. Conclusions The administration of GLN given immediately prior to MV may be beneficial in the context of reducing VILI. PMID:25589963

  6. The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction.

    PubMed

    Salah, Heba; Li, Meishan; Cacciani, Nicola; Gastaldello, Stefano; Ogilvie, Hannah; Akkad, Hazem; Namuduri, Arvind Venkat; Morbidoni, Valeria; Artemenko, Konstantin A; Balogh, Gabor; Martinez-Redondo, Vicente; Jannig, Paulo; Hedström, Yvette; Dworkin, Barry; Bergquist, Jonas; Ruas, Jorge; Vigh, Laszlo; Salviati, Leonardo; Larsson, Lars

    2016-08-01

    Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences for individual patients' quality of life and for the health care system, but specific treatment strategies are still lacking. We used an experimental intensive care unit (ICU) model, allowing time-resolved studies of diaphragm structure and function in response to long-term mechanical ventilation and the effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The marked loss of diaphragm muscle fiber function in response to mechanical ventilation was caused by posttranslational modifications (PTMs) of myosin. In a rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber function (by about 100%), although it did not reverse diaphragm atrophy. The treatment also provided protection from myosin PTMs associated with HSP72 induction and PARP-1 inhibition, resulting in improvement of mitochondrial function and content. Thus, BGP-15 may offer an intervention strategy for reducing VIDD in mechanically ventilated ICU patients.

  7. Trans Fatty Acids Induce Vascular Inflammation and Reduce Vascular Nitric Oxide Production in Endothelial Cells

    PubMed Central

    Iwata, Naomi G.; Pham, Matilda; Rizzo, Norma O.; Cheng, Andrew M.; Maloney, Ezekiel; Kim, Francis

    2011-01-01

    Intake of trans fatty acids (TFA), which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO) bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived—dairy products and meat) on endothelial NF-κB activation and nitric oxide (NO) production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans)), Linoelaidic (trans-C18:2 (9 trans, 12 trans)), and Transvaccenic (trans-C18:1 (11 trans)) for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses) did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation. PMID:22216328

  8. Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production.

    PubMed

    Lin, Ming-Chung; Lin, Chiou-Feng; Li, Chien-Feng; Sun, Ding-Ping; Wang, Li-Yun; Hsing, Chung-Hsi

    2015-05-27

    Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.

  9. Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia

    PubMed Central

    Yang, Ronghua; Sikka, Gautam; Larson, Jill; Watts, Vabren L.; Niu, Xiaolin; Ellis, Carla L.; Miller, Karen L.; Camara, Andre; Reinke, Christian; Savransky, Vladimir; Polotsky, Vsevolod Y.; O'Donnell, Christopher P.; Berkowitz, Dan E.

    2011-01-01

    Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH. PMID:21278136

  10. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

    SciTech Connect

    Goto, Hiromasa; Nomiyama, Takashi; Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Komiya, Koji; Arakawa, Masayuki; Jin, Wen Long; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Hirose, Takahisa; Watada, Hirotaka

    2011-02-04

    Research highlights: {yields} Exendin-4 reduces neointimal formation after vascular injury in a mouse model. {yields} Exendin-4 dose not alter metabolic parameters in non-diabetic, non-obese mouse model. {yields} Exendin-4 reduces PDGF-induced cell proliferation in cultured SMCs. {yields} Exendin-4 may reduces neointimal formation after vascular injury at least in part through its direct action on SMCs. -- Abstract: Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury. Under continuous infusion of exendin-4 at 24 nmol/kg/day, C57BL/6 mice were subjected to endothelial denudation injury of the femoral artery. Treatment of mice with exendin-4 reduced neointimal formation at 4 weeks after arterial injury without altering body weight or various metabolic parameters. In addition, in vitro studies of isolated murine, rat and human aortic vascular smooth muscle cells showed the expression of GLP-1 receptor. The addition of 10 nM exendin-4 to cultured smooth muscle cells significantly reduced their proliferation induced by platelet-derived growth factor. Our results suggested that exendin-4 reduced intimal thickening after vascular injury at least in part by the suppression of platelet-derived growth factor-induced smooth muscle cells proliferation.

  11. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase

    PubMed Central

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  12. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase.

    PubMed

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  13. Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy.

    PubMed

    Patel, C; Xu, Z; Shosha, E; Xing, J; Lucas, R; Caldwell, R W; Caldwell, R B; Narayanan, S P

    2016-09-01

    Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. New-born C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia. PMID:27239699

  14. Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

    PubMed Central

    Patel, C.; Xu, Z.; Shosha, E.; Xing, J.; Lucas, R.; Caldwell, R.W.; Caldwell, R.B.; Narayanan, S.P.

    2016-01-01

    Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. Newborn C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia. PMID:27239699

  15. Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

    PubMed

    Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

    2015-05-01

    Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels.

  16. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models

    PubMed Central

    Funahashi, Yasuhiro; Okamoto, Kiyoshi; Adachi, Yusuke; Semba, Taro; Uesugi, Mai; Ozawa, Yoichi; Tohyama, Osamu; Uehara, Taisuke; Kimura, Takayuki; Watanabe, Hideki; Asano, Makoto; Kawano, Satoshi; Tizon, Xavier; McCracken, Paul J; Matsui, Junji; Aoshima, Ken; Nomoto, Kenichi; Oda, Yoshiya

    2014-01-01

    Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models. Vascular remodeling associated with improved perfusion was shown by Hoechst 33342 staining and by increased microvessel density together with decreased mean vascular areas and fewer branched vessels in tumor tissues, as determined by immunohistochemical staining for endothelial marker CD31. Quantitative RT-PCR analysis of normal host cells in the stroma of xenograft tumors showed that eribulin altered the expression of mouse (host) genes in angiogenesis signaling pathways controlling endothelial cell–pericyte interactions, and in the epithelial–mesenchymal transition pathway in the context of the tumor microenvironment. Eribulin also decreased hypoxia-associated protein expression of mouse (host) vascular endothelial growth factor by ELISA and human CA9 by immunohistochemical analysis. Prior treatment with eribulin enhanced the anti-tumor activity of capecitabine in the MDA-MB-231 xenograft model. These findings suggest that eribulin-induced remodeling of abnormal tumor vasculature leads to a more functional microenvironment that may reduce the aggressiveness of tumors due to elimination of inner tumor hypoxia. Because abnormal tumor microenvironments enhance both drug resistance and metastasis, the apparent ability of eribulin to reverse these aggressive characteristics may contribute to its clinical benefits. PMID:25060424

  17. Association of reduced Connexin 43 expression with retinal vascular lesions in human diabetic retinopathy.

    PubMed

    Tien, Thomas; Muto, Tetsuya; Zhang, Joyce; Sohn, Elliott H; Mullins, Robert F; Roy, Sayon

    2016-05-01

    Connexin 43 (Cx43) downregulation promotes apoptosis in retinal vascular cells of diabetic animal models; however, its relevance to human diabetic retinopathy has not been established. In this study, we investigated whether diabetes alters Cx43 expression and promotes retinal vascular lesions in human retinas. Diabetic human eyes (aged 64-94 years) and non-diabetic human eyes (aged 61-90 years) were analyzed in this study. Retinal protein samples and retinal capillary networks were assessed for Cx43 level by Western blot (WB) analysis and immunostaining. In parallel, retinal capillary networks were stained with hematoxylin and periodic acid Schiff to determine the extent of pericyte loss (PL) and acellular capillaries (AC) in these retinas. Cx43 protein expression was significantly reduced in the diabetic retinas compared to non-diabetic retinas as indicated by WB analysis (81 ± 11% of control). Additionally, a significant decrease in the number of Cx43 plaques per unit length of vessel was observed in the diabetic retinas compared to those of non-diabetic retinas (62 ± 10% of control; p < 0.005). Importantly, a strong inverse relationship was noted between Cx43 expression and the relative number of AC (r = -0.89; p < 0.0005), and between Cx43 expression and number of pericyte loss (r = -0.88; p < 0.0005). Overall, these results show that Cx43 expression is reduced in the human diabetic retinas and Cx43 reduction is associated with increased vascular cell death. These findings suggest that diabetes decreases retinal Cx43 expression and that the development of PL and AC is associated with reduced Cx43 expression in human diabetic retinopathy. PMID:26738943

  18. High-Level Pressure Support Ventilation Attenuates Ventilator-Induced Diaphragm Dysfunction in Rabbits

    PubMed Central

    Ge, Huiqing; Xu, Peifeng; Zhu, Tao; Lu, Zhihua; Yuan, Yuehua; Zhou, Jiancang

    2015-01-01

    Abstract: Background: The effects of different modes of mechanical ventilation in the same ventilatory support level on ventilator-induced diaphragm dysfunction onset were assessed in healthy rabbits. Methods: Twenty New Zealand rabbits were randomly assigned to 4 groups (n = 5 in each group). Group 1: no mechanical ventilation; group 2: controlled mechanical ventilation (CMV) for 24 hours; group 3: assist/control ventilation (A/C) mode for 24 hours; group 4: high-level pressure support ventilation (PSV) mode for 24 hours. Heart rate, mean arterial blood pressure, PH, partial pressure of arterial oxygen/fraction of inspired oxygen and partial pressure of arterial carbon dioxide were monitored and diaphragm electrical activity was analyzed in the 4 groups. Caspase-3 was evaluated by protein analysis and diaphragm ultra structure was assessed by electron microscopy. Results: The centroid frequency and the ratio of high frequency to low frequency were significantly reduced in the CMV, A/C and PSV groups (P < 0.001). The percent change in centroid frequency was significantly lower in the PSV group than in the CMV and A/C groups (P = 0.001 and P = 0.028, respectively). Electromyography of diaphragm integral amplitude decreased by 90% ± 1.48%, 67.8% ± 3.13% and 70.2% ± 4.72% in the CMV, A/C and PSV groups, respectively (P < 0.001). Caspase-3 protein activation was attenuated in the PSV group compared with the CMV and A/C groups (P = 0.035 and P = 0.033, respectively). Irregular swelling of mitochondria along with fractured and fuzzy cristae was observed in the CMV group, whereas mitochondrial cristae were dense and rich in the PSV group. The mitochondrial injury scores (Flameng scores) in the PSV group were the lowest among the 3 ventilatory groups (0.93 ± 0.09 in PSV versus 2.69 ± 0.05 in the CMV [P < 0.01] and PSV versus A/C groups [2.02 ± 0.08, P < 0.01]). Conclusions: The diaphragm myoelectric activity was reduced in the PSV group, although excessive oxidative

  19. Postpartum Vascular Dysfunction in the Reduced Uteroplacental Perfusion Model of Preeclampsia

    PubMed Central

    Quon, Anita; Davidge, Sandra T.

    2016-01-01

    Preeclampsia is a disorder affecting 2–8% of all pregnancies, characterized by gestational hypertension (≥ 140/90 mmHg) and proteinuria (≥300 mg over 24 hours) diagnosed following the 20th week of pregnancy, and for which there is currently no available treatment. While the precise cause of preeclampsia is unknown, placental ischemia/hypoxia resulting from abnormal trophoblast invasion and maternal endothelial dysfunction are central characteristics. Preeclampsia is a major cause of both maternal and fetal morbidity and mortality in the perinatal period. In addition, women who have experienced preeclampsia are more likely to suffer cardiovascular disease later in life. The cause of this elevation in cardiovascular risk postpartum, however, is unknown. We hypothesize that there may be lasting vascular dysfunction following exposure to reduced uteroplacental perfusion during pregnancy that may contribute to increased cardiovascular risk postpartum. Using the rat reduced utero-placental perfusion pressure (RUPP) model of preeclampsia, blood pressure was assessed in dams at gestational day 20, one and three months postpartum. Mesenteric artery and aortic function were assessed using wire myography. We demonstrated hypertension and increased mesenteric artery responses to phenylephrine at gestational day 20, with the latter due to a decreased contribution of nitric oxide without any change in methylcholine-induced relaxation. At one month postpartum, we demonstrated a small but significant vasoconstrictive phenotype that was due to an underlying loss of basal nitric oxide contribution. At three months postpartum, endothelium-dependent relaxation of the aorta demonstrated sensitivity to oxLDL and mesenteric arteries demonstrated decreased nitric oxide bioavailability with impaired methylcholine-induced relaxation; indicative of an early development of endothelial dysfunction. In summary, we have demonstrated impaired vascular function following exposure to a RUPP

  20. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction

    PubMed Central

    Smith, Ira J.; Godinez, Guillermo L.; Singh, Baljit K.; McCaughey, Kelly M.; Alcantara, Raniel R.; Gururaja, Tarikere; Ho, Melissa S.; Nguyen, Henry N.; Friera, Annabelle M.; White, Kathy A.; McLaughlin, John R.; Hansen, Derek; Romero, Jason M.; Baltgalvis, Kristen A.; Claypool, Mark D.; Li, Wei; Lang, Wayne; Yam, George C.; Gelman, Marina S.; Ding, Rongxian; Yung, Stephanie L.; Creger, Daniel P.; Chen, Yan; Singh, Rajinder; Smuder, Ashley J.; Wiggs, Michael P.; Kwon, Oh-Sung; Sollanek, Kurt J.; Powers, Scott K.; Masuda, Esteban S.; Taylor, Vanessa C.; Payan, Donald G.; Kinoshita, Taisei; Kinsella, Todd M.

    2014-01-01

    ., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction. PMID:24671708

  1. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

    PubMed

    Smith, Ira J; Godinez, Guillermo L; Singh, Baljit K; McCaughey, Kelly M; Alcantara, Raniel R; Gururaja, Tarikere; Ho, Melissa S; Nguyen, Henry N; Friera, Annabelle M; White, Kathy A; McLaughlin, John R; Hansen, Derek; Romero, Jason M; Baltgalvis, Kristen A; Claypool, Mark D; Li, Wei; Lang, Wayne; Yam, George C; Gelman, Marina S; Ding, Rongxian; Yung, Stephanie L; Creger, Daniel P; Chen, Yan; Singh, Rajinder; Smuder, Ashley J; Wiggs, Michael P; Kwon, Oh-Sung; Sollanek, Kurt J; Powers, Scott K; Masuda, Esteban S; Taylor, Vanessa C; Payan, Donald G; Kinoshita, Taisei; Kinsella, Todd M

    2014-07-01

    ., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

  2. HABP2 is a Novel Regulator of Vascular Integrity

    PubMed Central

    Mambetsariev, N.; Mirzapoiazova, T.; Mambetsariev, B.; Sammani, S.; Lennon, F.E.; Garcia, J.G.N.; Singleton, P.A.

    2010-01-01

    Objective We evaluated the role of the extracellular serine protease, Hyaluronic Acid Binding Protein 2 (HABP2), in vascular barrier regulation. Methods and Results Using immunoblot and immunohistochemical analysis, we observed that lipopolysaccharide (LPS)-induces HABP2 expression in murine lung endothelium in vivo and in human pulmonary microvascular endothelial cell (HPMVEC) in vitro. High molecular weight hyaluronan (HMW-HA, ~1 million Da) decreased HABP2 protein expression in HPMVEC and decreased purified HABP2 enzymatic activity whereas low MW HA (LMW-HA, ~2,500 Da) increased these activities. The effects of LMW-HA on HABP2 activity, but not HMW-HA, were inhibited with a peptide of the polyanion binding domain (PABD) of HABP2. Silencing (siRNA) HABP2 expression augmented HMW-HA-induced EC barrier enhancement and inhibited LPS and LMW-HA-mediated EC barrier disruption, results which were reversed with overexpression of HABP2. Silencing PAR receptors 1 and 3, RhoA or ROCK expression attenuated LPS, LMW-HA and HABP2-mediated EC barrier disruption. Utilizing murine models of acute lung injury, we observed that LPS- and ventilator-induced pulmonary vascular hyper-permeability were significantly reduced with vascular silencing (siRNA) of HABP2. Conclusions HABP2 negatively regulates vascular integrity via activation of PAR receptor/RhoA/ROCK signaling and represents a potentially useful therapeutic target for syndromes of increased vascular permeability. PMID:20042707

  3. Breaking dogmas: the plant vascular pathogen Xanthomonas albilineans is able to invade non-vascular tissues despite its reduced genome.

    PubMed

    Mensi, Imène; Vernerey, Marie-Stéphanie; Gargani, Daniel; Nicole, Michel; Rott, Philippe

    2014-02-12

    Xanthomonas albilineans, the causal agent of sugarcane leaf scald, is missing the Hrp type III secretion system that is used by many Gram-negative bacteria to colonize their host. Until now, this pathogen was considered as strictly limited to the xylem of sugarcane. We used confocal laser scanning microscopy, immunocytochemistry and transmission electron microscopy (TEM) to investigate the localization of X. albilineans in diseased sugarcane. Sugarcane plants were inoculated with strains of the pathogen labelled with a green fluorescent protein. Confocal microscopy observations of symptomatic leaves confirmed the presence of the pathogen in the protoxylem and metaxylem; however, X. albilineans was also observed in phloem, parenchyma and bulliform cells of the infected leaves. Similarly, vascular bundles of infected sugarcane stalks were invaded by X. albilineans. Surprisingly, the pathogen was also observed in apparently intact storage cells of the stalk and in intercellular spaces between these cells. Most of these observations made by confocal microscopy were confirmed by TEM. The pathogen exits the xylem following cell wall and middle lamellae degradation, thus creating openings to reach parenchyma cells. This is the first description of a plant pathogenic vascular bacterium invading apparently intact non-vascular plant tissues and multiplying in parenchyma cells.

  4. Breaking dogmas: the plant vascular pathogen Xanthomonas albilineans is able to invade non-vascular tissues despite its reduced genome

    PubMed Central

    Mensi, Imène; Vernerey, Marie-Stéphanie; Gargani, Daniel; Nicole, Michel; Rott, Philippe

    2014-01-01

    Xanthomonas albilineans, the causal agent of sugarcane leaf scald, is missing the Hrp type III secretion system that is used by many Gram-negative bacteria to colonize their host. Until now, this pathogen was considered as strictly limited to the xylem of sugarcane. We used confocal laser scanning microscopy, immunocytochemistry and transmission electron microscopy (TEM) to investigate the localization of X. albilineans in diseased sugarcane. Sugarcane plants were inoculated with strains of the pathogen labelled with a green fluorescent protein. Confocal microscopy observations of symptomatic leaves confirmed the presence of the pathogen in the protoxylem and metaxylem; however, X. albilineans was also observed in phloem, parenchyma and bulliform cells of the infected leaves. Similarly, vascular bundles of infected sugarcane stalks were invaded by X. albilineans. Surprisingly, the pathogen was also observed in apparently intact storage cells of the stalk and in intercellular spaces between these cells. Most of these observations made by confocal microscopy were confirmed by TEM. The pathogen exits the xylem following cell wall and middle lamellae degradation, thus creating openings to reach parenchyma cells. This is the first description of a plant pathogenic vascular bacterium invading apparently intact non-vascular plant tissues and multiplying in parenchyma cells. PMID:24522883

  5. P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation

    PubMed Central

    Simion, Viorel; Constantinescu, Cristina Ana; Stan, Daniela; Deleanu, Mariana; Tucureanu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Simionescu, Maya

    2016-01-01

    Inflammation is a common process associated with numerous vascular pathologies. We hypothesized that targeting the inflamed endothelium by coupling a peptide with high affinity for P-selectin to the surface of dexamethasone-loaded lipid nanoemulsions will highly increase their specific binding to activated endothelial cells (EC) and reduce the cell activation. We developed and characterized dexamethasone-loaded lipid nanoemulsions directed towards P-selectin (PLN-Dex) and monitored their anti-inflammatory effects in vitro using cultured EC (EA.hy926 cells) and in vivo using a mouse model of acute inflammation [lipopolysaccharides (LPS) intravenously administered in C57BL/6 mice]. We found that PLN-Dex bound specifically to the surface of activated EC are efficiently internalized by EC and reduced the expression of proinflammatory genes, thus preventing the monocyte adhesion and transmigration to/through activated EC. Given intravenously in mice with acute inflammation, PLN-Dex accumulated at a significant high level in the lungs (compared to nontargeted nanoemulsions) and significantly reduced mRNA expression level of key proinflammatory cytokines such as IL-1β, IL-6, and MCP-1. In conclusion, the newly developed nanoformulation, PLN-Dex, is functional in vitro and in vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs' inflammation, in a mouse model of acute inflammation. PMID:27703301

  6. History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung Injury.

    PubMed

    Slutsky, Arthur S

    2015-05-15

    Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure. PMID:25844759

  7. History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung Injury.

    PubMed

    Slutsky, Arthur S

    2015-05-15

    Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

  8. Repeated exposure to heat stress results in a diaphragm phenotype that resists ventilator-induced diaphragm dysfunction.

    PubMed

    Yoshihara, Toshinori; Ichinoseki-Sekine, Noriko; Kakigi, Ryo; Tsuzuki, Takamasa; Sugiura, Takao; Powers, Scott K; Naito, Hisashi

    2015-11-01

    Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against CMV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.

  9. Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE(-/-) mice.

    PubMed

    Chan, Yee Kwan; El-Nezami, Hani; Chen, Yan; Kinnunen, Kristiina; Kirjavainen, Pirkka V

    2016-12-01

    Atherosclerosis results from chronic inflammation potentially caused by translocation of bacterial components from the oro-gastrointestinal tract to circulation. Specific probiotics have anti-inflammatory effects and may reduce bacterial translocation. We thereby tested whether a probiotic mixture with documented anti-inflammatory potential could reduce atherosclerosis. ApoE(-/-) mice were fed high fat diet alone or with VSL#3 or a positive control treatment, telmisartan or both for 12 weeks. All treatments reduced atherosclerotic plaques significantly compared to high fat diet alone. VSL#3 significantly reduced proinflammatory adhesion molecules and risk factors of plaque rupture, reduced vascular inflammation and atherosclerosis to a comparable extent to telmisartan; and VSL#3 treated mice had the most distinctly different intestinal microbiota composition from the control groups. Combining the VSL#3 and telmisartan brought no further benefits. Our findings showed the therapeutic potential of VSL#3 in reducing atherosclerosis and vascular inflammation. PMID:27576894

  10. Renin-angiotensin system in ventilator-induced diaphragmatic dysfunction: Potential protective role of Angiotensin (1-7).

    PubMed

    Sigurta', Anna; Zambelli, Vanessa; Bellani, Giacomo

    2016-09-01

    Ventilator-induced diaphragmatic dysfunction is a feared complication of mechanical ventilation that adversely affects the outcome of intensive care patients. Human and animal studies demonstrate atrophy and ultrastructural alteration of diaphragmatic muscular fibers attributable to increased oxidative stress, depression of the anabolic pathway regulated by Insulin-like growing factor 1 and increased proteolysis. The renin-angiotensin system, through its main peptide Angiotensin II, plays a major role in skeletal muscle diseases, mainly increasing oxidative stress and inducing insulin resistance, atrophy and fibrosis. Conversely, its counter-regulatory peptide Angiotensin (1-7) has a protective role in these processes. Recent data on rodent models show that renin-angiotensin system is activated after mechanical ventilation and that infusion of Angiotensin II induces diaphragmatic skeletal muscle atrophy. Given: (A) common pathways shared by ventilator-induced diaphragmatic dysfunction and skeletal muscle pathology induced by renin-angiotensin system, (B) evidences of an involvement of renin-angiotensin system in diaphragm atrophy and dysfunction, we hypothesize that renin-angiotensin system plays an important role in ventilator-induced diaphragmatic dysfunction, while Angiotensin (1-7) can have a protective effect on this pathological process. The activation of renin-angiotensin system in ventilator-induced diaphragmatic dysfunction can be demonstrated by quantification of its main components in the diaphragm of ventilated humans or animals. The infusion of Angiotensin (1-7) in an established rodent model of ventilator-induced diaphragmatic dysfunction can be used to test its potential protective role, that can be further confirmed with the infusion of Angiotensin (1-7) antagonists like A-779. Verifying this hypothesis can help in understanding the processes involved in ventilator-induced diaphragmatic dysfunction pathophysiology and open new possibilities for its

  11. Renin-angiotensin system in ventilator-induced diaphragmatic dysfunction: Potential protective role of Angiotensin (1-7).

    PubMed

    Sigurta', Anna; Zambelli, Vanessa; Bellani, Giacomo

    2016-09-01

    Ventilator-induced diaphragmatic dysfunction is a feared complication of mechanical ventilation that adversely affects the outcome of intensive care patients. Human and animal studies demonstrate atrophy and ultrastructural alteration of diaphragmatic muscular fibers attributable to increased oxidative stress, depression of the anabolic pathway regulated by Insulin-like growing factor 1 and increased proteolysis. The renin-angiotensin system, through its main peptide Angiotensin II, plays a major role in skeletal muscle diseases, mainly increasing oxidative stress and inducing insulin resistance, atrophy and fibrosis. Conversely, its counter-regulatory peptide Angiotensin (1-7) has a protective role in these processes. Recent data on rodent models show that renin-angiotensin system is activated after mechanical ventilation and that infusion of Angiotensin II induces diaphragmatic skeletal muscle atrophy. Given: (A) common pathways shared by ventilator-induced diaphragmatic dysfunction and skeletal muscle pathology induced by renin-angiotensin system, (B) evidences of an involvement of renin-angiotensin system in diaphragm atrophy and dysfunction, we hypothesize that renin-angiotensin system plays an important role in ventilator-induced diaphragmatic dysfunction, while Angiotensin (1-7) can have a protective effect on this pathological process. The activation of renin-angiotensin system in ventilator-induced diaphragmatic dysfunction can be demonstrated by quantification of its main components in the diaphragm of ventilated humans or animals. The infusion of Angiotensin (1-7) in an established rodent model of ventilator-induced diaphragmatic dysfunction can be used to test its potential protective role, that can be further confirmed with the infusion of Angiotensin (1-7) antagonists like A-779. Verifying this hypothesis can help in understanding the processes involved in ventilator-induced diaphragmatic dysfunction pathophysiology and open new possibilities for its

  12. Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function

    PubMed Central

    Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Jose V; Palacios, Roberto; Briones, Ana M; Miguel, Marta; Salaices, Mercedes; Alonso, María J

    2012-01-01

    BACKGROUND AND PURPOSE PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. EXPERIMENTAL APPROACH Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg−1·day−1, 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence. KEY RESULTS In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI2) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses. CONCLUSIONS AND IMPLICATIONS Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. PMID

  13. Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia.

    PubMed

    Bender, Shawn B; de Beer, Vincent J; Tharp, Darla L; van Deel, Elza D; Bowles, Douglas K; Duncker, Dirk J; Laughlin, M Harold; Merkus, Daphne

    2014-04-15

    Vascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailability. Since NO normally limits endothelin (ET) action, we examined the hypothesis that reduced systemic vasodilatation during exercise in FH swine results from increased ET-mediated vasoconstriction. Systemic and pulmonary vascular responses to exercise were examined in chronically instrumented normal and FH swine in the absence and presence of the ETA/B receptor antagonist tezosentan. Intrinsic reactivity to ET was further assessed in skeletal muscle arterioles. FH swine exhibited ∼9-fold elevation in total plasma cholesterol versus normal swine. Similar to our recent findings, systemic, not pulmonary, vasodilatation during exercise was reduced in FH swine. Blockade of ET receptors caused marked systemic vasodilatation at rest and during exercise in normal swine that was significantly reduced in FH swine. The reduced role of ET in FH swine in vivo was not the result of decreased arteriolar ET responsiveness, as responsiveness was increased in isolated arterioles. Smooth muscle ET receptor protein content was unaltered by FH. However, circulating plasma ET levels were reduced in FH swine. ET receptor antagonism caused pulmonary vasodilatation at rest and during exercise in normal, but not FH, swine. Therefore, contrary to our hypothesis, FH swine exhibit a generalised reduction in the role of ET in regulating vascular tone in vivo probably resulting from reduced ET production. This may represent a unique vascular consequence of severe familial hypercholesterolaemia.

  14. Exposure to mechanical ventilation promotes tolerance to ventilator-induced lung injury by Ccl3 downregulation.

    PubMed

    Blázquez-Prieto, Jorge; López-Alonso, Inés; Amado-Rodríguez, Laura; Batalla-Solís, Estefanía; González-López, Adrián; Albaiceta, Guillermo M

    2015-10-15

    Inflammation plays a key role in the development of ventilator-induced lung injury (VILI). Preconditioning with a previous exposure can damp the subsequent inflammatory response. Our objectives were to demonstrate that tolerance to VILI can be induced by previous low-pressure ventilation, and to identify the molecular mechanisms responsible for this phenomenon. Intact 8- to 12-wk-old male CD1 mice were preconditioned with 90 min of noninjurious ventilation [peak pressure 17 cmH2O, positive end-expiratory pressure (PEEP) 2 cmH2O] and extubated. Seven days later, preconditioned mice and intact controls were submitted to injurious ventilation (peak pressure 20 cmH2O, PEEP 0 cmH2O) for 2 h to induce VILI. Preconditioned mice showed lower histological lung injury scores, bronchoalveolar lavage albumin content, and lung neutrophilic infiltration after injurious ventilation, with no differences in Il6 or Il10 expression. Microarray analyses revealed a downregulation of Calcb, Hspa1b, and Ccl3, three genes related to tolerance phenomena, in preconditioned animals. Among the previously identified genes, only Ccl3, which encodes the macrophage inflammatory protein 1 alpha (MIP-1α), showed significant differences between intact and preconditioned mice after high-pressure ventilation. In separate, nonconditioned animals, treatment with BX471, a specific blocker of CCR1 (the main receptor for MIP-1α), decreased lung damage and neutrophilic infiltration caused by high-pressure ventilation. We conclude that previous exposure to noninjurious ventilation induces a state of tolerance to VILI. Downregulation of the chemokine gene Ccl3 could be the mechanism responsible for this effect.

  15. Reduced Anterior Cruciate Ligament Vascularization Is Associated With Chondral Knee Lesions.

    PubMed

    Hetsroni, Iftach; Manor, Amir; Finsterbush, Alex; Lowe, Joseph; Mann, Gideon; Palmanovich, Ezequiel

    2016-07-01

    This study tested the association between periligamentous vascularization of the anterior cruciate ligament (ACL) and the presence of chondral knee lesions via retrospective analysis of prospectively collected data from 702 consecutive knee arthroscopic procedures. In each case, the ACL periligamentous envelope was documented as follows: (1) vascular, where the ACL was covered with blood vessels along its entire length; (2) centrally avascular, where the central third of the ACL was not covered but peripheral vascularized coverage was present; and (3) avascular, where there was no blood vessel coverage of the ACL. Inclusion criteria for the study were as follows: (1) age older than 18 years and (2) normal knee ligament laxity. Univariate analysis and multiple logistic regression were used to test the association between chondral lesions and each of the variables: sex, age, meniscus tear, decreased ACL vascularity, and concomitant chondral lesion in another knee compartment. The cohort included 516 knees. In the univariate analysis, all variables were associated with a chondral lesion, but only older age and decreased ACL vascularity were associated with chondral lesions in each knee compartment. In the regression model, only decreased ACL vascularity was associated with chondral lesions in each knee compartment. For avascular knees, the odds ratio was 2.84 for medial femoral condyle lesions (95% confidence interval, 1.73-4.68; P=.000), 2.44 for lateral femoral condyle lesions (95% confidence interval, 1.19-5.03; P=.015), and 2.48 for patellofemoral lesions (95% confidence interval, 1.55-3.97; P=.000). The findings showed that decreased ACL periligamentous vascularization is associated with chondral lesions of the femoral condyles in knees with preserved ACL laxity. [Orthopedics. 2016; 39(4):e737-e743.]. PMID:27111071

  16. The effect of low level laser therapy on ventilator-induced lung injury in mice (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Szabari, Margit V.; Miller, Alyssa J.; Hariri, Lida P.; Hamblin, Michael R.; Musch, Guido; Stroh, Helene; Suter, Melissa J.

    2016-03-01

    Although mechanical ventilation (MV) is necessary to support gas exchange in critically ill patients, it can contribute to the development of lung injury and multiple organ dysfunction. It is known that high tidal volume (Vt) MV can cause ventilator-induced lung injury (VILI) in healthy lungs and increase the mortality of patients with Acute Respiratory Distress Syndrome. Low level laser therapy (LLLT) has demonstrated to have anti-inflammatory effects. We investigated whether LLLT could alleviate inflammation from injurious MV in mice. Adult mice were assigned to 2 groups: VILI+LLLT group (3 h of injurious MV: Vt=25-30 ml/kg, respiratory rate (RR)=50/min, positive end-expiratory pressure (PEEP)=0 cmH20, followed by 3 h of protective MV: Vt=9 ml/kg, RR=140/min, PEEP=2 cmH20) and VILI+no LLLT group. LLLT was applied during the first 30 min of the MV (810 nm LED system, 5 J/cm2, 1 cm above the chest). Respiratory impedance was measured in vivo with forced oscillation technique and lung mechanics were calculated by fitting the constant phase model. At the end of the MV, bronchoalveolar lavage (BAL) was performed and inflammatory cells counted. Lungs were removed en-bloc and fixed for histological evaluation. We hypothesize that LLLT can reduce lung injury and inflammation from VILI. This therapy could be translated into clinical practice, where it can potentially improve outcomes in patients requiring mechanical ventilation in the operating room or in the intensive care units.

  17. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis

    PubMed Central

    Derwall, Matthias; Malhotra, Rajeev; Lai, Carol S; Beppu, Yuko; Aikawa, Elena; Seehra, Jasbir S.; Zapol, Warren M; Bloch, Kenneth D.; Yu, Paul B.

    2012-01-01

    Objective The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. While genetic gain- and loss-of-function experiments in mice have supported a causal role of BMP signaling in atherosclerosis and vascular calcification, it remains uncertain whether BMP signaling might be targeted pharmacologically to ameliorate both of these processes. Methods and Results We tested the impact of pharmacologic BMP inhibition upon atherosclerosis and calcification in low density lipoprotein receptor-deficient (LDLR−/−) mice. LDLR−/− mice fed a high-fat diet developed abundant vascular calcification within twenty weeks. Prolonged treatment of LDLR−/− mice with the small molecule BMP inhibitor LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Administration of recombinant BMP antagonist ALK3-Fc replicated the anti-atherosclerotic and anti-inflammatory effects of LDN-193189. Treatment of human aortic endothelial cells with LDN-193189 or ALK3-Fc abrogated the production of reactive oxygen species (ROS) induced by oxidized LDL, a known early event in atherogenesis. Unexpectedly, treatment of mice with LDN-193189 lowered LDL serum cholesterol by 35% and markedly decreased hepatosteatosis without inhibiting HMG-CoA reductase activity. Treatment with BMP2 increased, whereas LDN-193189 or ALK3-Fc inhibited apolipoprotein B100 secretion in HepG2 cells, suggesting that BMP signaling contributes to the regulation of cholesterol biosynthesis. Conclusions These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification. PMID:22223731

  18. Quantitative Analyses of Retinal Vascular Area and Density After Different Methods to Reduce VEGF in a Rat Model of Retinopathy of Prematurity

    PubMed Central

    Wang, Haibo; Yang, Zhihong; Jiang, Yanchao; Flannery, John; Hammond, Scott; Kafri, Tal; Vemuri, Sai Karthik; Jones, Bryan; Hartnett, M. Elizabeth

    2014-01-01

    Purpose. Targeted inhibition of Müller cell (MC)–produced VEGF or broad inhibition of VEGF with an intravitreal anti-VEGF antibody reduces intravitreal neovascularization in a rat model of retinopathy of prematurity (ROP). In this study, we compared the effects of these two approaches on retinal vascular development and capillary density in the inner and deep plexi in the rat ROP model. Methods. In the rat model of ROP, pups received 1 μL of (1) subretinal lentivector-driven short hairpin RNA (shRNA) to knockdown MC-VEGFA (VEGFA.shRNA) or control luciferase shRNA, or (2) intravitreal anti-VEGF antibody (anti-VEGF) or control isotype goat immunoglobulin G (IgG). Analyses of lectin-stained flat mounts at postnatal day 18 (p18) included: vascular/total retinal areas (retinal vascular coverage) and pixels of fluorescence/total retinal area (capillary density) of the inner and deep plexi determined with the Syncroscan microscope, and angles between cleavage planes of mitotic vascular figures labeled with anti-phosphohistone H3 and vessel length. Results. Retinal vascular coverage and density increased in both plexi between p8 and p18 in room air (RA) pups. Compared with RA, p18 ROP pups had reduced vascular coverage and density of both plexi. Compared with respective controls, VEGFA.shRNA treatment significantly increased vascular density in the deep plexus, whereas anti-VEGF reduced vascular density in the inner and deep plexi. Vascular endothelial growth factor-A.shRNA caused more cleavage angles predicting vessel elongation and fewer mitotic figures, whereas anti-VEGF treatment led to patterns of pathologic angiogenesis. Conclusions. Targeted treatment with lentivector-driven VEGFA.shRNA permitted physiologic vascularization of the vascular plexi and restored normal orientation of dividing vascular cells, suggesting that regulation of VEGF signaling by targeted treatment may be beneficial. PMID:24425858

  19. Bixin protects mice against ventilation-induced lung injury in an NRF2-dependent manner

    PubMed Central

    Tao, Shasha; Rojo de la Vega, Montserrat; Quijada, Hector; Wondrak, Georg T.; Wang, Ting; Garcia, Joe G. N.; Zhang, Donna D.

    2016-01-01

    Mechanical ventilation (MV) is a therapeutic intervention widely used in the clinic to assist patients that have difficulty breathing due to lung edema, trauma, or general anesthesia. However, MV causes ventilator-induced lung injury (VILI), a condition characterized by increased permeability of the alveolar-capillary barrier that results in edema, hemorrhage, and neutrophil infiltration, leading to exacerbated lung inflammation and oxidative stress. This study explored the feasibility of using bixin, a canonical NRF2 inducer identified during the current study, to ameliorate lung damage in a murine VILI model. In vitro, bixin was found to activate the NRF2 signaling pathway through blockage of ubiquitylation and degradation of NRF2 in a KEAP1-C151 dependent manner; intraperitoneal (IP) injection of bixin led to pulmonary upregulation of the NRF2 response in vivo. Remarkably, IP administration of bixin restored normal lung morphology and attenuated inflammatory response and oxidative DNA damage following MV. This observed beneficial effect of bixin derived from induction of the NRF2 cytoprotective response since it was only observed in Nrf2+/+ but not in Nrf2−/− mice. This is the first study providing proof-of-concept that NRF2 activators can be developed into pharmacological agents for clinical use to prevent patients from lung injury during MV treatment. PMID:26729554

  20. Targeting Heat Shock Proteins Mitigates Ventilator Induced Diaphragm Muscle Dysfunction in an Age-Dependent Manner

    PubMed Central

    Ogilvie, Hannah; Cacciani, Nicola; Akkad, Hazem; Larsson, Lars

    2016-01-01

    Intensive care unit (ICU) patients are often overtly subjected to mechanical ventilation and immobilization, which leads to impaired limb and respiratory muscle function. The latter, termed ventilator-induced diaphragm dysfunction (VIDD) has recently been related to compromised heat shock protein (Hsp) activation. The administration of a pharmacological drug BGP-15 acting as a Hsp chaperone co-inducer has been found to partially alleviate VIDD in young rats. Considering that the mean age in the ICU is increasing, we aimed to explore whether the beneficial functional effects are also present in old rats. For that, we exposed young (7–8 months) and old (28–32 months) rats to 5-day controlled mechanical ventilation and immobilization with or without systemic BGP-15 administration. We then dissected diaphragm muscles, membrane–permeabilized bundles and evaluated the contractile function at single fiber level. Results confirmed that administration of BGP-15 restored the force-generating capacity of isolated muscle cells from young rats in conjunction with an increased expression of Hsp72. On the other hand, our results highlighted that old rats did not positively respond to the BGP-15 treatment. Therefore, it is of crucial importance to comprehend in more depth the effect of VIDD on diaphragm function and ascertain any further age-related differences. PMID:27729867

  1. Genetic Targets of Hydrogen Sulfide in Ventilator-Induced Lung Injury – A Microarray Study

    PubMed Central

    Spassov, Sashko; Pfeifer, Dietmar; Strosing, Karl; Ryter, Stefan; Hummel, Matthias; Faller, Simone; Hoetzel, Alexander

    2014-01-01

    Recently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical ventilation in the absence or presence of H2S (80 parts per million). Gene expression profiles were determined by microarray, sqRT-PCR and Western Blot analyses. The association of Atf3 in protection against VILI was confirmed with a Vivo-Morpholino knockout model. Mechanical ventilation caused a significant lung inflammation and damage that was prevented in the presence of H2S. Mechanical ventilation favoured the expression of genes involved in inflammation, leukocyte activation and chemotaxis. In contrast, ventilation with H2S activated genes involved in extracellular matrix remodelling, angiogenesis, inhibition of apoptosis, and inflammation. Amongst others, H2S administration induced Atf3, an anti-inflammatory and anti-apoptotic regulator. Morpholino mediated reduction of Atf3 resulted in elevated lung injury despite the presence of H2S. In conclusion, lung protection by H2S during mechanical ventilation is associated with down-regulation of genes related to oxidative stress and inflammation and up-regulation of anti-apoptotic and anti-inflammatory genes. Here we show that Atf3 is clearly involved in H2S mediated protection. PMID:25025333

  2. The JAK–STAT Pathway Is Critical in Ventilator-Induced Diaphragm Dysfunction

    PubMed Central

    Tang, Huibin; Smith, Ira J; Hussain, Sabah NA; Goldberg, Peter; Lee, Myung; Sugiarto, Sista; Godinez, Guillermo L; Singh, Baljit K; Payan, Donald G; Rando, Thomas A; Kinsella, Todd M; Shrager, Joseph B

    2014-01-01

    Mechanical ventilation (MV) is one of the lynchpins of modern intensive-care medicine and is life saving in many critically ill patients. Continuous ventilator support, however, results in ventilation-induced diaphragm dysfunction (VIDD) that likely prolongs patients’ need for MV and thereby leads to major associated complications and avoidable intensive care unit (ICU) deaths. Oxidative stress is a key pathogenic event in the development of VIDD, but its regulation remains largely undefined. We report here that the JAK–STAT pathway is activated in MV in the human diaphragm, as evidenced by significantly increased phosphorylation of JAK and STAT. Blockage of the JAK–STAT pathway by a JAK inhibitor in a rat MV model prevents diaphragm muscle contractile dysfunction (by ~85%, p < 0.01). We further demonstrate that activated STAT3 compromises mitochondrial function and induces oxidative stress in vivo, and, interestingly, that oxidative stress also activates JAK–STAT. Inhibition of JAK–STAT prevents oxidative stress-induced protein oxidation and polyubiquitination and recovers mitochondrial function in cultured muscle cells. Therefore, in ventilated diaphragm muscle, activation of JAK–STAT is critical in regulating oxidative stress and is thereby central to the downstream pathogenesis of clinical VIDD. These findings establish the molecular basis for the therapeutic promise of JAK–STAT inhibitors in ventilated ICU patients. PMID:25286450

  3. Reduced number of caudate nucleus dopamine uptake sites in vascular dementia.

    PubMed

    Allard, P; Englund, E; Marcusson, J

    1999-01-01

    The dopamine (DA) uptake sites in the caudate nucleus were studied in patients with vascular dementia (VAD) and in a control group using the presynaptic DA uptake site marker [3H][2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane] as radioligand. There was a significant decrease in the number of DA uptake sites in the VAD group, while the binding affinity was unchanged. The present results indicate that in the patients investigated, the cerebrovascular disease process involves dopaminergic neuron terminals in the caudate nucleus. Our findings are discussed in relation to the reductions in number of DA uptake sites that have previously been revealed in Alzheimer's and Parkinson's diseases.

  4. Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits

    PubMed Central

    He, Yi-Xin; Liu, Jin; Guo, Baosheng; Wang, Yi-Xiang; Pan, Xiaohua; Li, Defang; Tang, Tao; Chen, Yang; Peng, Songlin; Bian, Zhaoxiang; Liang, Zicai; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

    2015-01-01

    To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement & Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement & Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement & Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis. PMID:25748225

  5. Histamine reduces GPIbα-mediated adhesion of platelets to TNF-α-activated vascular endothelium.

    PubMed

    Brown, T P; Forouzan, O; Shevkoplyas, S S; Khismatullin, D B

    2013-02-01

    Histamine and tumor necrosis factor-α (TNF-α) are critical mediators of acute and chronic inflammation that are generated by mast cells and macrophages in atherosclerotic lesions or systemically during allergic attacks. Both of them induce activation of vascular endothelium and thus may play a role in thrombosis. Here we studied the interplay between histamine and TNF-α in glycoprotein (GP) Ibα-mediated platelet adhesion to cultured human vascular endothelial cells under static and shear flow conditions. The stimulation of endothelial cells with histamine or TNF-α increased the number of adherent or slow rolling GP Ibα-coated microbeads or washed human platelets. However, the application of histamine to endothelium pre-activated by TNF-α inhibited GP Ibα-mediated platelet adhesion. These effects were found to be associated with changes in the concentration of ultra large von Willebrand factor (ULVWF) strings anchored to endothelium. The results of this study indicate that histamine released during mast cell degranulation may cause or inhibit thrombosis, depending on whether it acts on resting endothelial cells or on cells pre-activated by other inflammatory stimuli.

  6. Gastrointestinal Inhibition of Sodium-Hydrogen Exchanger 3 Reduces Phosphorus Absorption and Protects against Vascular Calcification in CKD

    PubMed Central

    Labonté, Eric D.; Carreras, Christopher W.; Leadbetter, Michael R.; Kozuka, Kenji; Kohler, Jill; Koo-McCoy, Samantha; He, Limin; Dy, Edward; Black, Deborah; Zhong, Ziyang; Langsetmo, Ingrid; Spencer, Andrew G.; Bell, Noah; Deshpande, Desiree; Navre, Marc; Lewis, Jason G.; Jacobs, Jeffrey W.

    2015-01-01

    In CKD, phosphate retention arising from diminished GFR is a key early step in a pathologic cascade leading to hyperthyroidism, metabolic bone disease, vascular calcification, and cardiovascular mortality. Tenapanor, a minimally systemically available inhibitor of the intestinal sodium-hydrogen exchanger 3, is being evaluated in clinical trials for its potential to (1) lower gastrointestinal sodium absorption, (2) improve fluid overload-related symptoms, such as hypertension and proteinuria, in patients with CKD, and (3) reduce interdialytic weight gain and intradialytic hypotension in ESRD. Here, we report the effects of tenapanor on dietary phosphorous absorption. Oral administration of tenapanor or other intestinal sodium-hydrogen exchanger 3 inhibitors increased fecal phosphorus, decreased urine phosphorus excretion, and reduced [33P]orthophosphate uptake in rats. In a rat model of CKD and vascular calcification, tenapanor reduced sodium and phosphorus absorption and significantly decreased ectopic calcification, serum creatinine and serum phosphorus levels, circulating phosphaturic hormone fibroblast growth factor-23 levels, and heart mass. These results indicate that tenapanor is an effective inhibitor of dietary phosphorus absorption and suggest a new approach to phosphate management in renal disease and associated mineral disorders. PMID:25404658

  7. Gastrointestinal Inhibition of Sodium-Hydrogen Exchanger 3 Reduces Phosphorus Absorption and Protects against Vascular Calcification in CKD.

    PubMed

    Labonté, Eric D; Carreras, Christopher W; Leadbetter, Michael R; Kozuka, Kenji; Kohler, Jill; Koo-McCoy, Samantha; He, Limin; Dy, Edward; Black, Deborah; Zhong, Ziyang; Langsetmo, Ingrid; Spencer, Andrew G; Bell, Noah; Deshpande, Desiree; Navre, Marc; Lewis, Jason G; Jacobs, Jeffrey W; Charmot, Dominique

    2015-05-01

    In CKD, phosphate retention arising from diminished GFR is a key early step in a pathologic cascade leading to hyperthyroidism, metabolic bone disease, vascular calcification, and cardiovascular mortality. Tenapanor, a minimally systemically available inhibitor of the intestinal sodium-hydrogen exchanger 3, is being evaluated in clinical trials for its potential to (1) lower gastrointestinal sodium absorption, (2) improve fluid overload-related symptoms, such as hypertension and proteinuria, in patients with CKD, and (3) reduce interdialytic weight gain and intradialytic hypotension in ESRD. Here, we report the effects of tenapanor on dietary phosphorous absorption. Oral administration of tenapanor or other intestinal sodium-hydrogen exchanger 3 inhibitors increased fecal phosphorus, decreased urine phosphorus excretion, and reduced [(33)P]orthophosphate uptake in rats. In a rat model of CKD and vascular calcification, tenapanor reduced sodium and phosphorus absorption and significantly decreased ectopic calcification, serum creatinine and serum phosphorus levels, circulating phosphaturic hormone fibroblast growth factor-23 levels, and heart mass. These results indicate that tenapanor is an effective inhibitor of dietary phosphorus absorption and suggest a new approach to phosphate management in renal disease and associated mineral disorders.

  8. Human pulmonary vascular and venous compliances are reduced before and during left-sided heart failure.

    PubMed

    Hirakawa, S; Suzuki, T; Gotoh, K; Ito, H; Tanaka, T; Ohsumi, Y; Yagi, Y; Terashima, Y; Fujiwara, H; Nagashima, K

    1995-01-01

    Human pulmonary vascular and venous compliances were measured in 41 patients with or without left-sided heart failure. Two methods were used. Method 1 was based on analysis of pulmonary capillary wedge (PCW) pressure tracings according to Cv,PCW = (SF/100)(0.075PCW + 0.90)SV/[(v - d)PCW + 1], where Cv,PCW is compliance of pulmonary venous system, SF is systolic fraction of pulmonary venous flow [related to pulmonary capillary wedge pressure (PCW) as SF = 82 - 2.01PCW], (v - d)PCW is pulse pressure in PCW position, and SV is stroke volume. The (0.075PCW + 0.90) term equals k", i.e., systolic run-off ratio. Method 2 was used to measure to pulmonary vascular volume-pressure (V-P) relationship and pulmonary vascular compliance (Cvasc) and is based on measurement of pulmonary blood volume (PBV) and its increase with passive elevation of the legs to calculate Cvasc. Assuming the proportion of blood entering pulmonary venous system (in increase of PBV) during passive leg elevation to be 0.8, pulmonary venous compliance (Cv,PBV) was calculated as Cv,PBV = 0.8Cvasc. Cv,PCW correlated fairly closely with Cv,PBV (r = 0.81, coefficient of variation = 31%). This fair agreement between two independent methods suggests strongly that both methods may be valid, although other interpretations are possible. Cv,PCW, Cvasc, and Cv,PBV decreased going from New York Heart Association class I to classes II and III. When PBV was plotted vs. PCW, average V-P line for class II patients was flatter and shifted downward to the right compared with that for class I. This suggests pulmonary vasoconstriction as well as other factors. Average V-P line for class III patients is flatter but not displaced compared with that for class II. Another previously reported series of 50 patients, most of whom had ischemic heart disease, are included in this study. PMID:7713833

  9. Role of intrinsic aerobic capacity and ventilator-induced diaphragm dysfunction

    PubMed Central

    Sollanek, Kurt J.; Smuder, Ashley J.; Wiggs, Michael P.; Morton, Aaron B.; Koch, Lauren G.; Britton, Steven L.

    2015-01-01

    Prolonged mechanical ventilation (MV) leads to rapid diaphragmatic atrophy and contractile dysfunction, which is collectively termed “ventilator-induced diaphragm dysfunction” (VIDD). Interestingly, endurance exercise training prior to MV has been shown to protect against VIDD. Further, recent evidence reveals that sedentary animals selectively bred to possess a high aerobic capacity possess a similar skeletal muscle phenotype to muscles from endurance trained animals. Therefore, we tested the hypothesis that animals with a high intrinsic aerobic capacity would naturally be afforded protection against VIDD. To this end, animals were selectively bred over 33 generations to create two divergent strains, differing in aerobic capacity: high-capacity runners (HCR) and low-capacity runners (LCR). Both groups of animals were subjected to 12 h of MV and compared with nonventilated control animals within the same strains. As expected, contrasted to LCR animals, the diaphragm muscle from the HCR animals contained higher levels of oxidative enzymes (e.g., citrate synthase) and antioxidant enzymes (e.g., superoxide dismutase and catalase). Nonetheless, compared with nonventilated controls, prolonged MV resulted in significant diaphragmatic atrophy and impaired diaphragm contractile function in both the HCR and LCR animals, and the magnitude of VIDD did not differ between strains. In conclusion, these data demonstrate that possession of a high intrinsic aerobic capacity alone does not afford protection against VIDD. Importantly, these results suggest that endurance exercise training differentially alters the diaphragm phenotype to resist VIDD. Interestingly, levels of heat shock protein 72 did not differ between strains, thus potentially representing an important area of difference between animals with intrinsically high aerobic capacity and exercise-trained animals. PMID:25571991

  10. Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury.

    PubMed

    Kuethe, Dean O; Filipczak, Piotr T; Hix, Jeremy M; Gigliotti, Andrew P; Estépar, Raúl San José; Washko, George R; Baron, Rebecca M; Fredenburgh, Laura E

    2016-08-01

    Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 ± 1.6 h) than it was detected by altered lung mechanics (9.5 ± 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration (P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI.

  11. Elevated matrix metalloprotease and angiostatin levels in integrin α1 knockout mice cause reduced tumor vascularization

    PubMed Central

    Pozzi, Ambra; Moberg, Philip E.; Miles, Lindsey A.; Wagner, Simone; Soloway, Paul; Gardner, Humphrey A.

    2000-01-01

    Integrin α1β1 is a collagen receptor abundantly expressed on microvascular endothelial cells. As well as being the only collagen receptor able to activate the Ras/Shc/mitogen-activated protein kinase pathway promoting fibroblast cell proliferation, it also acts to inhibit collagen and metalloproteinase (MMP) synthesis. We have observed that in integrin α1-null mice synthesis of MMP7 and MMP9 was markedly increased compared with that of their wild-type counterparts. As MMP7 and MMP9 have been shown to generate angiostatin from circulating plasminogen, and angiostatin acts as a potent inhibitor of endothelial cell proliferation, we determined whether tumor vascularization was altered in the α1-null mice. Tumors implanted into α1-null mice showed markedly decreased vascularization, with a reduction in capillary number and size, which was accompanied by an increase in plasma levels of angiostatin due to the action of MMP7 and MMP9 on circulating plasminogen. In vitro analysis of α1-null endothelial cells revealed a marked reduction of their proliferation on both integrin α1-dependent (collagenous) and independent (noncollagenous) substrata. This reduction was prevented by culturing α1-null cells with plasma derived from plasminogen-null animals, thus omitting the source from which to generate angiostatin. Plasma from tumor-bearing α1-null animals uniquely inhibited endothelial cell growth, and this inhibition was relieved by the coaddition of either MMP inhibitors, or antibody to angiostatin. Integrin α1-deficient mice thus provide a genetically characterized model for enhanced angiostatin production and serve to reveal an unwanted potential side effect of MMP inhibition, increased tumor angiogenesis. PMID:10681423

  12. Alkylglycerols reduce serum complement and plasma vascular endothelial growth factor in obese individuals.

    PubMed

    Parri, A; Fitó, Montserrat; Torres, C F; Muñoz-Aguayo, D; Schröder, H; Cano, J F; Vázquez, L; Reglero, G; Covas, María-Isabel

    2016-06-01

    Alkylglycerols (AKGs), isolated or present in shark liver oil have anti-inflammatory properties. Complement 3 (C3) and 4 (C4) participate in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low-grade inflammation associated with obesity. In a randomized, controlled, crossover study, 26 non-diabetes obese individuals were assigned two preparations with low (LAC, 10 mg AKGs) and high (HAC, 20 mg AKGs) AKG content. Intervention periods were of 3 weeks preceded by 2-week washout periods in which shark liver oil was avoided. Cholesterol, C3, C4, and vascular endothelial growth factor (VEGF) decreased in a linear trend (P < 0.01) from baseline (control) to LAC and HAC. Values after HAC were significantly lower (P < 0.05) versus both baseline and after LAC. No adverse effects were observed or reported. Data from this pilot study open a promising field for the study of the beneficial effects of AKGs on cardiovascular risk factors in obese individuals. PMID:27188987

  13. Alkylglycerols reduce serum complement and plasma vascular endothelial growth factor in obese individuals.

    PubMed

    Parri, A; Fitó, Montserrat; Torres, C F; Muñoz-Aguayo, D; Schröder, H; Cano, J F; Vázquez, L; Reglero, G; Covas, María-Isabel

    2016-06-01

    Alkylglycerols (AKGs), isolated or present in shark liver oil have anti-inflammatory properties. Complement 3 (C3) and 4 (C4) participate in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low-grade inflammation associated with obesity. In a randomized, controlled, crossover study, 26 non-diabetes obese individuals were assigned two preparations with low (LAC, 10 mg AKGs) and high (HAC, 20 mg AKGs) AKG content. Intervention periods were of 3 weeks preceded by 2-week washout periods in which shark liver oil was avoided. Cholesterol, C3, C4, and vascular endothelial growth factor (VEGF) decreased in a linear trend (P < 0.01) from baseline (control) to LAC and HAC. Values after HAC were significantly lower (P < 0.05) versus both baseline and after LAC. No adverse effects were observed or reported. Data from this pilot study open a promising field for the study of the beneficial effects of AKGs on cardiovascular risk factors in obese individuals.

  14. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with Osteogenesis Imperfecta

    PubMed Central

    Jameson, John; Smith, Peter; Harris, Gerald

    2015-01-01

    Osteogenesis Imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64–68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3–42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (p≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight towards understanding bone fragility and the role of intracortical porosity on the strength of bone

  15. Autologous transplantation of adipose-derived stromal cells ameliorates ventilator-induced lung injury in rats

    PubMed Central

    2013-01-01

    Background Adipose-derived stromal cells (ADSCs) are a good alternative to multipotent stem cells for regenerative medicine. Low tidal volume (LVT) has proved to be an effective ventilation strategy. However, it is not known if ADSCs and LVT can protect against ventilator-induced lung injury (VILI). This study was aimed to determine the potential of ADSCs and LVT to repair following VILI and to elucidate the mechanisms responsible for this section. Methods A total of 72 rats were randomly assigned into group I (sham group, n = 18), group II (1 h of high tidal volume-ventilated (HVT) 40 mL/kg to peak airway pressures of approximately 35 cm H2O and 100% oxygen, n = 18), group III (1 h of HVT followed by 6 h LVT 6 mL/kg to peak airway pressures of approximately 6 cm H2O and 100% oxygen, n = 18) and group IV (1 h of HVT followed by intravenous injection of 5 × 106 ADSCs, n = 18). All animals were sacrificed 7 after the experiments lasted for 7 hours. Bronchoalveolar lavage fluid (BALF) was collected and lungs were harvested for analysis. Results High tidal volume-ventilated (HVT) rats exhibited typical VILI features compared with sham rats. Lung edema, histological lung injury index, concentrations of total protein, total cell counts, number of neutrophils in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-10 and transforming growth factor-β1 in BALF were significantly increased in HVT rats. Additionally, gene and protein levels of Na+ channel subunits, Na-K-ATPase pump activity and alveolar fluid clearance were significantly decreased in HVT rats. All these indices of VILI were significantly improved in rats treated with ADSCs. However, compared with ADSCs treatment, LVT strategy had little therapeutic effect in the present study. Conclusion These results may provide valuable insights into the effects of ADSCs in acute lung injury. PMID:23890086

  16. Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways

    SciTech Connect

    Aguado, Andrea; Galán, María; Zhenyukh, Olha; Wiggers, Giulia A.; Roque, Fernanda R.; Redondo, Santiago; Peçanha, Franck; Martín, Angela; Fortuño, Ana; Cachofeiro, Victoria; Tejerina, Teresa; Salaices, Mercedes; and others

    2013-04-15

    Mercury exposure is known to increase cardiovascular risk but the underlying cellular mechanisms remain undetermined. We analyzed whether chronic exposure to HgCl{sub 2} affects vascular structure and the functional properties of vascular smooth muscle cells (VSMC) through oxidative stress/cyclooxygenase-2 dependent pathways. Mesenteric resistance arteries and aortas from Wistar rats treated with HgCl{sub 2} (first dose 4.6 mg kg{sup −1}, subsequent doses 0.07 mg kg{sup −1} day{sup −1}, 30 days) and cultured aortic VSMC stimulated with HgCl{sub 2} (0.05–5 μg/ml) were used. Treatment of rats with HgCl{sub 2} decreased wall thickness of the resistance and conductance vasculature, increased the number of SMC within the media and decreased SMC nucleus size. In VSMCs, exposure to HgCl{sub 2}: 1) induced a proliferative response and a reduction in cell size; 2) increased superoxide anion production, NADPH oxidase activity, gene and/or protein levels of the NADPH oxidase subunit NOX-1, the EC- and Mn-superoxide dismutases and cyclooxygenase-2 (COX-2); 3) induced activation of ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized the proliferative response and the altered cell size induced by HgCl{sub 2}. Blockade of ERK1/2 and p38 signaling pathways abolished the HgCl{sub 2}-induced Nox1 and COX-2 expression and normalized the alterations induced by mercury in cell proliferation and size. In conclusion, long exposure of VSMC to low doses of mercury activates MAPK signaling pathways that result in activation of inflammatory proteins such as NADPH oxidase and COX-2 that in turn induce proliferation of VSMC and changes in cell size. These findings offer further evidence that mercury might be considered an environmental risk factor for cardiovascular disease. - Highlights: ► Chronic HgCl{sub 2} exposure induces vascular remodeling. ► HgCl{sub 2} induces proliferation and decreased cell size in vascular smooth muscle cells. ► HgCl{sub 2} induces

  17. Effects of MMP-9 inhibition by doxycycline on proteome of lungs in high tidal volume mechanical ventilation-induced acute lung injury

    PubMed Central

    2010-01-01

    Background Although mechanical ventilation (MV) is a major supportive therapy for patients with acute respiratory distress syndrome, it may result in side effects including lung injury. In this study we hypothesize that MMP-9 inhibition by doxycycline might reduce MV-related lung damage. Using a proteomic approach we identified the pulmonary proteins altered in high volume ventilation-induced lung injury (VILI). Forty Wistar rats were randomized to an orally pretreated with doxycycline group (n = 20) or to a placebo group (n = 20) each of which was followed by instrumentation prior to either low or high tidal volume mechanical ventilation. Afterwards, animals were euthanized and lungs were harvested for subsequent analyses. Results Mechanical function and gas exchange parameters improved following treatment with doxycycline in the high volume ventilated group as compared to the placebo group. Nine pulmonary proteins have shown significant changes between the two biochemically analysed (high volume ventilated) groups. Treatment with doxycycline resulted in a decrease of pulmonary MMP-9 activity as well as in an increase in the levels of soluble receptor for advanced glycation endproduct, apoliporotein A-I, peroxiredoxin II, four molecular forms of albumin and two unnamed proteins. Using the pharmacoproteomic approach we have shown that treatment with doxycycline leads to an increase in levels of several proteins, which could potentially be part of a defense mechanism. Conclusion Administration of doxycycline might be a significant supportive therapeutic strategy in prevention of VILI. PMID:20205825

  18. Human recombinant vascular endothelial growth factor reduces necrosis and enhances hepatocyte regeneration in a mouse model of acetaminophen toxicity.

    PubMed

    Donahower, Brian C; McCullough, Sandra S; Hennings, Leah; Simpson, Pippa M; Stowe, Cindy D; Saad, Ali G; Kurten, Richard C; Hinson, Jack A; James, Laura P

    2010-07-01

    We reported previously that vascular endothelial growth factor (VEGF) was increased in acetaminophen (APAP) toxicity in mice and treatment with a VEGF receptor inhibitor reduced hepatocyte regeneration. The effect of human recombinant VEGF (hrVEGF) on APAP toxicity in the mouse was examined. In early toxicity studies, B6C3F1 mice received hrVEGF (50 microg s.c.) or vehicle 30 min before receiving APAP (200 mg/kg i.p.) and were sacrificed at 2, 4, and 8 h. Toxicity was comparable at 2 and 4 h, but reduced in the APAP/hrVEGF mice at 8 h (p < 0.05) compared with the APAP/vehicle mice. Hepatic glutathione (GSH) and APAP protein adduct levels were comparable between the two groups of mice, with the exception that GSH was higher at 8 h in the hrVEGF-treated mice. Subsequently, mice received two doses (before and 10 h) or three doses (before and 10 and 24 h) of hrVEGF; alanine aminotransferase values and necrosis were reduced at 24 and 36 h, respectively, in the APAP/hrVEGF mice (p < 0.05) compared with the APAP/vehicle mice. Proliferating cell nuclear antigen expression was enhanced, and interleukin-6 expression was reduced in the mice that received hrVEGF (p < 0.05) compared with the APAP/vehicle mice. In addition, treatment with hrVEGF lowered plasma hyaluronic acid levels and neutrophil counts at 36 h. Cumulatively, the data show that treatment with hrVEGF reduced toxicity and increased hepatocyte regeneration in APAP toxicity in the mouse. Attenuation of sinusoidal cell endothelial dysfunction and changes in neutrophil dynamics may be operant mechanisms in the hepatoprotection mediated by hrVEGF in APAP toxicity.

  19. TGF-β receptor 1 inhibition prevents stenosis of tissue-engineered vascular grafts by reducing host mononuclear phagocyte activation.

    PubMed

    Lee, Yong-Ung; de Dios Ruiz-Rosado, Juan; Mahler, Nathan; Best, Cameron A; Tara, Shuhei; Yi, Tai; Shoji, Toshihiro; Sugiura, Tadahisa; Lee, Avione Y; Robledo-Avila, Frank; Hibino, Narutoshi; Pober, Jordan S; Shinoka, Toshiharu; Partida-Sanchez, Santiago; Breuer, Christopher K

    2016-07-01

    Stenosis is a critical problem in the long-term efficacy of tissue-engineered vascular grafts (TEVGs). We previously showed that host monocyte infiltration and activation within the graft drives stenosis and that TGF-β receptor 1 (TGF-βR1) inhibition can prevent it, but the latter effect was attributed primarily to inhibition of mesenchymal cell expansion. In this study, we assessed the effects of TGF-βR1 inhibition on the host monocytes. Biodegradable TEVGs were implanted as inferior vena cava interposition conduits in 2 groups of C57BL/6 mice (n = 25/group): unseeded grafts and unseeded grafts with TGF-βR1 inhibitor systemic treatment for the first 2 wk. The TGF-βR1 inhibitor treatment effectively improved TEVG patency at 6 mo compared to the untreated control group (91.7 vs. 48%, P < 0.001), which is associated with a reduction in classic activation of mononuclear phagocytes. Consistent with these findings, the addition of rTGF-β to LPS/IFN-γ-stimulated monocytes enhanced secretion of inflammatory cytokines TNF-α, IL-12, and IL-6; this effect was blocked by TGF-βR1 inhibition (P < 0.0001). These findings suggest that the TGF-β signaling pathway contributes to TEVG stenosis by inducing classic activation of host monocytes. Furthermore, blocking monocyte activation by TGF-βR1 inhibition provides a viable strategy for preventing TEVG stenosis while maintaining neotissue formation.-Lee, Y.-U., de Dios Ruiz-Rosado, J., Mahler, N., Best, C. A., Tara, S., Yi, T., Shoji, T., Sugiura, T., Lee, A. Y., Robledo-Avila, F., Hibino, N., Pober, J. S., Shinoka, T., Partida-Sanchez, S., Breuer, C. K. TGF-β receptor 1 inhibition prevents stenosis of tissue-engineered vascular grafts by reducing host mononuclear phagocyte activation. PMID:27059717

  20. FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy

    PubMed Central

    Deliyanti, Devy; Zhang, Yuan; Khong, Fay; Berka, David R.; Stapleton, David I.; Kelly, Darren J.; Wilkinson-Berka, Jennifer L.

    2015-01-01

    Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011 would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension due to an overactive extra-renal renin-angiotensin system. Diabetic rats were studied for 8 and 32 weeks and received intravitreal injections of FT011 (50 μM) or vehicle (0.9% NaCl). Comparisons were to age-matched controls. In the 8-week study, retinal inflammation was examined by quantitating vascular leukocyte adherence, microglial/macrophage density and the expression of inflammatory mediators. Macroglial Müller cells, which exhibit a pro-inflammatory and pro-angiogenic phenotype in diabetes, were evaluated in the 8-week study as well as in culture following exposure to hyperglycaemia and FT011 (10, 30, 100 μM) for 72 hours. In the 32-week study, severe retinal vasculopathy was examined by quantitating acellular capillaries and extracellular matrix proteins. In diabetic rats, FT011 reduced retinal leukostasis, microglial density and mRNA levels of intercellular adhesion molecule-1 (ICAM-1). In Müller cells, FT011 reduced diabetes-induced gliosis and vascular endothelial growth factor (VEGF) immunolabeling and the hyperglycaemic-induced increase in ICAM-1, monocyte chemoattractant protein-1, CCL20, cytokine-induced neutrophil chemoattractant-1, VEGF and IL-6. Late intervention with FT011 reduced acellular capillaries and the elevated mRNA levels of collagen IV and fibronectin in diabetic rats. In conclusion, the protective effects of FT011 in cardiorenal disease extend to key elements of diabetic retinopathy and

  1. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    PubMed Central

    2012-01-01

    Background Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders. PMID:22676316

  2. Reduced vascular nitric oxide-cGMP signaling contributes to adipose tissue inflammation during high-fat feeding

    PubMed Central

    Handa, Priya; Tateya, Sanshiro; Rizzo, Norma O.; Cheng, Andrew M.; Morgan-Stevenson, Vicki; Han, Chang-Yeop; Clowes, Alexander W.; Daum, Guenter; O’Brien, Kevin D.; Schwartz, Michael W.; Chait, Alan; Kim, Francis

    2012-01-01

    Rationale Obesity is characterized by chronic inflammation of adipose tissue, which contributes to insulin resistance and diabetes. Although nitric oxide (NO) signaling has anti-inflammatory effects in the vasculature, whether reduced NO contributes to adipose tissue inflammation is unknown. We sought to determine whether 1) obesity induced by high-fat (HF) diet reduces endothelial nitric oxide signaling in adipose tissue, 2) reduced endothelial nitric oxide synthase (eNOS) signaling is sufficient to induce adipose tissue inflammation independent of diet, and 3) increased cGMP signaling can block adipose tissue inflammation induced by HF feeding. Methods and results Relative to mice fed a low-fat diet, HF diet markedly reduced phospho-eNOS and phospho-VASP, markers of vascular NO signaling. Expression of pro-inflammatory cytokines was increased in adipose tissue of eNOS−/− mice. Conversely, enhancement of signaling downstream of NO by phosphodiesterase 5 (PDE-5) inhibition using sildenafil attenuated HF-induced pro-inflammatory cytokine expression and the recruitment of macrophages into adipose tissue. Finally, we implicate a role for Vasodilator- stimulated phosphoprotein (VASP), a downstream mediator of NO-cGMP signaling in mediating eNOS-induced anti-inflammatory effects since VASP−/− mice recapitulated the pro-inflammatory phenotype displayed by eNOS−/− mice. Conclusions These results imply a physiological role for endothelial NO to limit obesity-associated inflammation in adipose tissue and hence identifies the NO-cGMP-VASP pathway as a potential therapeutic target in the treatment of diabetes. PMID:21903940

  3. Identification of Risk Factors for Vascular Thrombosis May Reduce Early Renal Graft Loss: A Review of Recent Literature

    PubMed Central

    Keller, Anna Krarup; Jorgensen, Troels Munch; Jespersen, Bente

    2012-01-01

    Renal graft survival has improved over the past years, mainly owing to better immunosuppression. Vascular thrombosis, though rare, therefore accounts for up to one third of early graft loss. We assess current literature on transplantation, identify thrombosis risk factors, and discuss means of avoiding thrombotic events and saving thrombosed grafts. The incidence of arterial thrombosis was reported to 0.2–7.5% and venous thrombosis 0.1–8.2%, with the highest incidence among children and infants, and the lowest in living donor reports. The most significant risk factors for developing thrombosis were donor-age below 6 or above 60 years, or recipient-age below 5-6 years, per- or postoperative hemodynamic instability, peritoneal dialysis, diabetic nephropathy, a history of thrombosis, deceased donor, or >24 hours cold ischemia. Multiple arteries were not a risk factor, and a right kidney graft was most often reported not to be. Given the thrombosed kidney graft is diagnosed in time, salvage is possible by urgent reoperation and thrombectomy. Despite meticulous attentions to reduce thrombotic risk factors, thrombosis cannot be entirely prevented and means to an early detection of this complication is desirable in order to save the kidneys through prompt reoperation. Microdialysis may be a new tool for this. PMID:22701162

  4. Reducing the data: Analysis of the role of vascular geometry on blood flow patterns in curved vessels

    NASA Astrophysics Data System (ADS)

    Alastruey, Jordi; Siggers, Jennifer H.; Peiffer, Véronique; Doorly, Denis J.; Sherwin, Spencer J.

    2012-03-01

    Three-dimensional simulations of blood flow usually produce such large quantities of data that they are unlikely to be of clinical use unless methods are available to simplify our understanding of the flow dynamics. We present a new method to investigate the mechanisms by which vascular curvature and torsion affect blood flow, and we apply it to the steady-state flow in single bends, helices, double bends, and a rabbit thoracic aorta based on image data. By calculating forces and accelerations in an orthogonal coordinate system following the centreline of each vessel, we obtain the inertial forces (centrifugal, Coriolis, and torsional) explicitly, which directly depend on vascular curvature and torsion. We then analyse the individual roles of the inertial, pressure gradient, and viscous forces on the patterns of primary and secondary velocities, vortical structures, and wall stresses in each cross section. We also consider cross-sectional averages of the in-plane components of these forces, which can be thought of as reducing the dynamics of secondary flows onto the vessel centreline. At Reynolds numbers between 50 and 500, secondary motions in the directions of the local normals and binormals behave as two underdamped oscillators. These oscillate around the fully developed state and are coupled by torsional forces that break the symmetry of the flow. Secondary flows are driven by the centrifugal and torsional forces, and these are counterbalanced by the in-plane pressure gradients generated by the wall reaction. The viscous force primarily opposes the pressure gradient, rather than the inertial forces. In the axial direction, and depending on the secondary motion, the curvature-dependent Coriolis force can either enhance or oppose the bulk of the axial flow, and this shapes the velocity profile. For bends with little or no torsion, the Coriolis force tends to restore flow axisymmetry. The maximum circumferential and axial wall shear stresses along the centreline

  5. Infection of vascular endothelial cells with herpes simplex virus enhances tissue factor activity and reduces thrombomodulin expression.

    PubMed Central

    Key, N S; Vercellotti, G M; Winkelmann, J C; Moldow, C F; Goodman, J L; Esmon, N L; Esmon, C T; Jacob, H S

    1990-01-01

    Latent infection of vascular cells with herpes-viruses may play a pathogenic role in the development of human atherosclerosis. In a previous study, we found that cultured human umbilical vein endothelial cells (HUVECs) infected with herpes simplex virus 1 (HSV-1) became procoagulant, exemplified both by their enhanced assembly of the prothrombinase complex and by their inability to reduce adhesion of platelets. We now report two further procoagulant consequences of endothelial HSV infection: loss of surface thrombomodulin (TM) activity and induction of synthesis of tissue factor. Within 4 hr of infection of HUVECs, TM activity measured by thrombin-dependent protein C activation declined 21 +/- 3% (P less than 0.05) and by 18 hr, 48 +/- 5% (P less than 0.001). Similar significant TM decrements accompanied infection of bovine aortic endothelial cells. Identical TM loss was induced with HSV-2 infection but not with adenovirus infection. Decreased surface expression of TM antigen (measured by the specific binding of a polyclonal antibody to bovine TM) closely paralleled the loss of TM activity. As examined by Northern blotting, these losses apparently reflected rapid onset (within 4 hr of HSV infection) loss of mRNA for TM. In contrast, HSV infection induced a viral-dose-dependent increase in synthesis of tissue factor protein, adding to the procoagulant state. The results indicate that loss of endothelial protein-synthetic capacity is not a universal effect of HSV infection. We suggest that the procoagulant state induced by reduction in TM activity and amplified tissue factor activity accompanying HSV infection of endothelium could contribute to deposition of thrombi on atherosclerotic plaques and to the "coagulant-necrosis" state that characterizes HSV-infected mucocutaneous lesions. Images PMID:2169619

  6. Development of an auxiliary system for the execution of vascular catheter interventions with a reduced radiological risk; system description and first experimental results.

    PubMed

    Placidi, Giuseppe; Franchi, Danilo; Marsili, Luca; Gallo, Pasquale

    2007-11-01

    Vascular catheterization is a common procedure in clinical medicine. It is normally performed by a specialist using an X-ray fluoroscopic guide and contrast-media. In the present paper, an image-guided navigation system which indicates a path providing guidance to the desired target inside the vascular tree is described with the aim of reducing the exposure of personnel and patients to X-rays during the catheterization procedure. A 3D model of the patient vascular tree, reconstructed with data collected by an angiography before starting the intervention, is used as a guide map instead of fluoroscopic scans. An accurate spatial correspondence between the body of the patient and the 3D reconstructed vascular model is established and, by means of a position indicator installed over the catheter tip, the real-time position/orientation of the tip is indicated correctly. This paper describes the system and the operational procedures necessary to use the proposed method efficiently during a catheter intervention. Preliminary experimental results on a phantom are also reported.

  7. Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model

    PubMed Central

    Breuer, Thomas; Hatam, Nima; Grabiger, Benjamin; Marx, Gernot; Behnke, Bradley J.; Weis, Joachim; Kopp, Ruedger; Gayan-Ramirez, Ghislaine; Zoremba, Norbert; Bruells, Christian S.

    2016-01-01

    Perioperative necessity of deep sedation is inevitably associated with diaphragmatic inactivation. This study investigated 1) the feasibility of a new phrenic nerve stimulation method allowing early diaphragmatic activation even in deep sedation and, 2) metabolic changes within the diaphragm during mechanical ventilation compared to artificial activity. 12 piglets were separated into 2 groups. One group was mechanically ventilated for 12 hrs (CMV) and in the second group both phrenic nerves were stimulated via pacer wires inserted near the phrenic nerves to mimic spontaneous breathing (STIM). Lactate, pyruvate and glucose levels were measured continuously using microdialysis. Oxygen delivery and blood gases were measured during both conditions. Diaphragmatic stimulation generated sufficient tidal volumes in all STIM animals. Diaphragm lactate release increased in CMV transiently whereas in STIM lactate dropped during this same time point (2.6 vs. 0.9 mmol L−1 after 5:20 hrs; p < 0.001). CMV increased diaphragmatic pyruvate (40 vs. 146 μmol L−1 after 5:20 hrs between CMV and STIM; p < 0.0001), but not the lactate/pyruvate ratio. Diaphragmatic stimulation via regular electrodes is feasible to generate sufficient ventilation, even in deep sedation. Mechanical ventilation alters the metabolic state of the diaphragm, which might be one pathophysiologic origin of ventilator-induced diaphragmatic dysfunction. Occurrence of hypoxia was unlikely. PMID:27759115

  8. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) reduces vascular endothelial growth factor expression in allergen-induced airway inflammation.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Seoung Ju; Lee, Ho Kyung; Park, Hee Sun; Min, Kyung Hoon; Jin, Sun Mi; Lee, Yong Chul

    2006-06-01

    Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of bronchial asthma. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been implicated in regulating cell survival signaling through the phosphoinositide 3-kinase (PI3K)/Akt pathway. The key role of PI3K in VEGF-mediated signal transduction is established. However, the effects of PTEN on VEGF-mediated signaling in asthma are unknown. This study aimed to determine the effect of PI3K inhibitors and PTEN on VEGF expression in allergen-induced airway inflammation. We have used a female C57BL/6 mouse model for asthma to determine the role of PTEN in allergen-induced airway inflammation, specifically in the expression of VEGF. Allergen-induced airway inflammation leads to increased activity of PI3K in lung tissue. These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways; airway hyper-responsiveness; increased expression of interleukin (IL)-4, IL-5, IL-13, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, regulated on activation normal T cell expressed and secreted (RANTES), and eotaxin; increased vascular permeability; and increased levels of VEGF. Administration of PI3K inhibitors or adenoviruses carrying PTEN cDNA reduced the symptoms of asthma and decreased the increased levels of plasma extravasation and VEGF in allergen-induced asthmatic lungs. These results indicate that PTEN reduces VEGF expression in allergen-induced airway inflammation.

  9. Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats

    PubMed Central

    Loring, Stephen H.; Pecchiari, Matteo; Valle, Patrizia Della; Monaco, Ario; Gentile, Guendalina; D'Angelo, Edgardo

    2014-01-01

    Objective To see whether in acute lung injury (ALI) 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury (VILI), and 2) maintaining end-expiratory transpulmonary pressure (Pl) by increasing positive end-expiratory pressure (PEEP) reduces the deleterious effects of chest wall constriction. Design Experimental study in rats. Setting Physiology laboratory. Interventions ALI was induced in 3 groups of 9 rats by saline lavage. Nine animals immediately sacrificed served as control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with PEEP raised to maintain end-expiratory Pl. After lavage, all groups were ventilated with the same pattern for 1½ hr. Measurements and Main Results Pl, measured with an esophageal balloon-catheter, lung volume changes, arterial blood gasses and pH were assessed during mechanical ventilation (MV). Lung wet-to-dry ratio (W/D), albumin, TNF-α, IL-1β, IL-6, IL-10, and MIP-2 in serum and bronchoalveolar lavage fluid (BALF), and serum E-selectin and von Willebrand Factor (vWF) were measured at the end of MV. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged MV, lung mechanics, hypoxemia, and W/D were significantly worse in group LC. Pro-inflammatory cytokines except E-selectin were elevated in serum and BALF in all groups, with significantly greater levels of TNF-α, IL-1β, and IL-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed Pl than other groups. Conclusions Chest wall constriction in ALI reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, pro-inflammatory mediator release, and histological signs of VILI. Maintaining end-expiratory Pl at preconstriction

  10. Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

    SciTech Connect

    Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong Tang Jian

    2007-11-16

    Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE{sup -/-} mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.

  11. Multifocal vascular lesions.

    PubMed

    Levin, Laura E; Lauren, Christine T

    2016-03-01

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

  12. A Cyclooxygenase-2 Inhibitor Reduces Vascular Wall Thickness and Ameliorates Cognitive Impairment in a Cerebral Small Vessel Diseases Rat Model.

    PubMed

    Tang, Jie; Xiao, Weizhong; Li, Qinghua; Deng, Qiuqiong; Chu, Xinquan; Chen, Yang; Pan, Danhong; Fu, Jianhui

    2015-01-01

    Cerebral small vessel disease (CSVD) is a group of diseases that originate from changes in cerebral small vessels and that cause many conditions, such as cognitive impairment. However, there is no effective therapy for these diseases. Recent studies have suggested that inflammation is associated with this disease. Cyclooxygenase-2 (cox-2) is an inflammatory mediator; however, whether a cox-2 inhibitor could protect against the CSVD progression remains unknown. In the present study, stroke-prone spontaneously hypertensive rats (SHRsp) were used as a model of CSVD, and Sprague Dawley (SD) rats served as the control. SHRsp were treated with the cox-2 inhibitor celecoxib or vehicle. The Morris water maze test was performed, and vascular morphometry and the expression of collagen I and fibronectin were examined in cerebral small vessels and cerebral tissue. The results revealed that thickened small veesel walls, increased expression of collagen I and fibronectin and impaired cognitive function in SHRsp compared with SD rats. Additionally, celecoxib significantly down-regulated the expression of collagen I and fibronectin, attenuated the increase in vascular wall thickness and ameliorates the cognitive impairment. Our study indicated that this cox-2 inhibitor may serve as a promising candidate for the pharmacological intervention of CSVD. PMID:26159203

  13. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  14. Vascular Cures

    MedlinePlus

    ... Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High ...

  15. Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.

    PubMed

    de Beer, F M; Aslami, H; Hoeksma, J; van Mierlo, G; Wouters, D; Zeerleder, S; Roelofs, J J T H; Juffermans, N P; Schultz, M J; Lagrand, W K

    2014-11-01

    Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury. PMID:24760631

  16. Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells123

    PubMed Central

    Warner, Emily F; Zhang, Qingzhi; Raheem, K Saki; O’Hagan, David; O’Connell, Maria A; Kay, Colin D

    2016-01-01

    Background: Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. Objective: We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). Method: Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 μM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-α). The active metabolites were further studied for their response at different concentrations (0.01 μM–100 μM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 μM. Results: Of the 20 compounds screened at 1 μM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (−17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2–36.5% between 1 and 100 μM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2–54.7% between 10 and 100 μM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 μM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 μM PCA. Mixtures of the metabolites showed no

  17. [Vascular parkinsonism].

    PubMed

    Marxreiter, F; Winkler, J

    2016-07-01

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

  18. Pretreatment of synthetic vascular grafts with heparin before implantation, a simple technique to reduce the risk of thrombosis.

    PubMed

    Gerrah, Rabin; Sunstrom Pa-C, Rachel E; Hohimer, Alan R

    2015-10-01

    Thrombosis of synthetic grafts commonly used in cardiovascular surgery is a major complication. We examined whether pretreatment of the graft with heparin reduces the risk of early thrombosis. A circuit was assembled to compare two pairs of shunts simultaneously in the same animal. The study shunts were pretreated with heparin. After 2 hours of circulation, clot formation was evaluated by image analysis techniques. The pretreated grafts had fewer blood clots adhered to the surface by direct visual inspection. The image analysis showed 5 vs. 39 clots, 0.01% vs. 1.8% clotted area, and 62 vs. 5630 clot pixel area between the treated and non-treated grafts respectively, p < 0.05. Pretreatment of the synthetic graft with heparin prior to implantation reduces the risk of early clot formation. This simple practice might be helpful to prevent initial thrombosis of the graft and later occlusion.

  19. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  20. Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway

    PubMed Central

    Nallasamy, Palanisamy; Si, Hongwei; Babu, Pon Velayutham Anandh; Pan, Dengke; Fu, Yu; Brooke, Elizabeth A.S.; Shah, Halley; Zhen, Wei; Zhu, Hong; Liu, Dongmin; Li, Yunbo; Jia, Zhenquan

    2014-01-01

    Sulforaphane, a naturally-occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as 0.5 μM significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVECs), a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of sulforaphane also significantly suppressed TNF-α-induced production of monocyte chemotactic protein-1 (MCP-1), adhesion molecule sVCAM-1 and sE-Selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, sulforaphane inhibited TNF-α-induced NF-κB transcriptional activity, IκBα degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit inflammation by suppressing NF-κB signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers’ delicate organization as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that sulforaphane treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of sulforaphane may be, at least in part, associated with interfering with the NF-κB pathway. PMID:24880493

  1. Copper Oxide Nanoparticles Reduce Vasculogenesis in Transgenic Zebrafish Through Down-Regulation of Vascular Endothelial Growth Factor Expression and Induction of Apoptosis.

    PubMed

    Chang, Jie; Ichihara, Gaku; Shimada, Yasuhito; Tada-Oikawa, Saeko; Kuroyanagi, Junya; Zhang, Beibei; Suzuki, Yuka; Sehsah, Radwa; Kato, Masashi; Tanaka, Toshio; Ichihara, Sahoko

    2015-03-01

    The present study investigated the effects of exposure to metal oxide nanoparticles on vasculogenesis/angiogenesis using transgenic zebrafish. The study also examined the potential mechanisms involved in those effects using human umbilical vein endothelial cells (HUVEC). TG (nacre/fli1:EGFP) zebrafish were exposed to nano-sized titanium dioxide (TiO2), silica dioxide (SiO2), and copper oxide (CuO) particles at 0.01, 1 and 100 µg/ml concentrations from 1 to 5 dpf (day-post-fertilization). Angiogenesis was evaluated morphologically at the end of exposure. Exposure to CuO nanoparticles reduced the number of transversely-running subintestinal vessels in TG zebrafish. Exposure to CuO nanoparticles down-regulated the expression of vascular endothelial growth factor (VEGF) and VEGF receptor in endothelial cells sorted by Fluorescence Activated Cell Sorter (FACS). Exposure of HUVEC to CuO nanoparticles reduced cell viability and increased apoptotic index in a dose-dependent manner. The results suggested that CuO nanoparticles inhibit vasculogenesis through reduction of VEGF expression and induction of apoptosis.

  2. Loss of Vascular Endothelial Growth Factor A (VEGFA) Isoforms in Granulosa Cells Using pDmrt-1-Cre or Amhr2-Cre Reduces Fertility by Arresting Follicular Development and by Reducing Litter Size in Female Mice

    PubMed Central

    Sargent, Kevin M.; Lu, Ningxia; Clopton, Debra T.; Pohlmeier, William E.; Brauer, Vanessa M.; Ferrara, Napoleone; Silversides, David W.; Cupp, Andrea S.

    2015-01-01

    Because VEGFA has been implicated in follicle development, the objective of this study was to determine the effects of granulosa- and germ cell-specific VEGFA loss on ovarian morphogenesis, function, and female fertility. pDmrt1-Cre mice were mated to floxed VEGFA mice to develop granulosa-/germ cell-specific knockouts (pDmrt1-Cre;Vegfa-/-). The time from mating to first parturition was increased when pDmrt1-Cre;Vegfa-/- females were mated to control males (P = 0.0008) and tended to be longer for heterozygous females (P < 0.07). Litter size was reduced for pDmrt1-Cre;Vegfa-/- females (P < 0.007). The time between the first and second parturitions was also increased for heterozygous females (P < 0.04) and tended to be increased for pDmrt1-Cre;Vegfa-/- females (P < 0.07). pDmrt1-Cre;Vegfa-/- females had smaller ovaries (P < 0.04), reduced plasma estradiol (P < 0.007), fewer developing follicles (P < 0.008) and tended to have fewer corpora lutea (P < 0.08). Expression of Igf1r was reduced (P < 0.05); expression of Foxo3a tended to be increased (P < 0.06); and both Fshr (P < 0.1) and Sirt6 tended to be reduced (P < 0.06) in pDmrt1-Cre;Vegfa-/- ovaries. To compare VEGFA knockouts, we generated Amhr2-Cre;Vegfa-/- mice that required more time from mating to first parturition (P < 0.003) with variable ovarian size. Both lines had more apoptotic granulosa cells, and vascular staining did not appear different. Taken together these data indicate that the loss of all VEGFA isoforms in granulosa/germ cells (proangiogenic and antiangiogenic) causes subfertility by arresting follicular development, resulting in reduced ovulation rate and fewer pups per litter. PMID:25658474

  3. Pioglitazone reduces angiotensin II-induced COX-2 expression through inhibition of ROS production and ET-1 transcription in vascular cells from spontaneously hypertensive rats.

    PubMed

    Pérez-Girón, Jose V; Palacios, Roberto; Martín, Angela; Hernanz, Raquel; Aguado, Andrea; Martínez-Revelles, Sonia; Barrús, María T; Salaices, Mercedes; Alonso, María J

    2014-06-01

    Glitazones have anti-inflammatory properties by interfering with the transcription of proinflammatory genes, such as cyclooxygenase (COX)-2, and with ROS production, which are increased in hypertension. This study analyzed whether pioglitazone modulates COX-2 expression in hypertension by interfering with ROS and endothelin (ET)-1. In vivo, pioglitazone (2.5 mg·kg(-1)·day(-1), 28 days) reduced the greater levels of COX-2, pre-pro-ET-1, and NADPH oxidase (NOX) expression and activity as well as O2 (·-) production found in aortas from spontaneously hypertensive rats (SHRs). ANG II increased COX-2 and pre-pro-ET-1 levels more in cultured vascular smooth muscle cells from hypertensive rats compared with normotensive rats. The ETA receptor antagonist BQ-123 reduced ANG II-induced COX-2 expression in SHR cells. ANG II also increased NOX-1 expression, NOX activity, and superoxide production in SHR cells; the selective NOX-1 inhibitor ML-171 and catalase reduced ANG II-induced COX-2 and ET-1 transcription. ANG II also increased c-Jun transcription and phospho-JNK1/2, phospho-c-Jun, and p65 NF-κB subunit nuclear protein expression. SP-600125 and lactacystin, JNK and NF-κB inhibitors, respectively, reduced ANG II-induced ET-1, COX-2, and NOX-1 levels and NOX activity. Pioglitazone reduced the effects of ANG II on NOX activity, NOX-1, pre-pro-ET-1, COX-2, and c-Jun mRNA levels, JNK activation, and nuclear phospho-c-Jun and p65 expression. In conclusion, ROS production and ET-1 are involved in ANG II-induced COX-2 expression in SHRs, explaining the greater COX-2 expression observed in this strain. Furthermore, pioglitazone inhibits ANG II-induced COX-2 expression likely by interfering with NF-κB and activator protein-1 proinflammatory pathways and downregulating ROS production and ET-1 transcription, thus contributing to the anti-inflammatory properties of glitazones.

  4. Chronic vagus nerve stimulation attenuates vascular endothelial impairments and reduces the inflammatory profile via inhibition of the NF-κB signaling pathway in ovariectomized rats.

    PubMed

    Li, Ping; Liu, Huaipu; Sun, Peng; Wang, Xiaoyu; Wang, Chen; Wang, Ling; Wang, Tinghuai

    2016-02-01

    Vagus nerve stimulation (VNS), a method for activating cholinergic anti-inflammatory pathways, could suppress endothelial activation and minimize tissue injury during inflammation. The aim of this study was to investigate the effects of chronic VNS on endothelial impairments and the inflammatory profile in ovariectomized (OVX) rats. Sprague-Dawley rats (7-8 months old) were randomly assigned to the following four groups: sham-OVX, OVX, OVX+sham-VNS, and OVX+VNS. Throughout the experimental period, the OVX+VNS group received VNS for 3h (20.0 Hz, 1.0 mA, and 10.00 ms pulse width) at the same time every other day. After 12 weeks of VNS, blood samples and thoracic aortas were collected for further analyses. Light microscopy and electron microscopy analyses showed that chronic VNS prevented endothelial swelling, desquamation and even necrosis in the OVX rats. In addition, it obviously improved endothelial function in the OVX rats by restoring the endothelial nitric oxide synthase (e-NOS) and serum endothelin-1 level. Increased expression of cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin) in the thoracic aortas and increases in the levels of circulating cytokines (TNF-α, IL-6, MCP-1, and CINC/KC) were also observed in the OVX rats. Chronic VNS significantly restored these detrimental changes partly by increasing the ACh concentrations in vascular walls and blocking NF-κB pathway activity. The results of this in vivo study have shown that the administration of chronic VNS during, in the early stage of estrogen deficiency, protects OVX rats from endothelial impairments and the inflammatory profile. These findings indicate that activation of the vagus nerve could be a promising supplemental therapy for reducing the risks of suffering from further CVDs in postmenopausal women. PMID:26692419

  5. Arginase inhibition reduces interleukin-1β-stimulated vascular smooth muscle cell proliferation by increasing nitric oxide synthase-dependent nitric oxide production

    SciTech Connect

    Yoon, Jeongyeon; Ryoo, Sungwoo

    2013-06-07

    Highlights: •Arginase inhibition suppressed proliferation of IL-1β-stimulated VSMCs in dose-dependent manner. •NO production from IL-1β-induced iNOS expression was augmented by arginase inhibition, reducing VSMC proliferation. •Incubation with cGMP analogues abolished IL-1β-dependent proliferation of VSMCs. -- Abstract: We investigated whether arginase inhibition suppressed interleukin (IL)-1β-stimulated proliferation in vascular smooth muscle cells (VSMCs) and the possible mechanisms involved. IL-1β stimulation increased VSMC proliferation, while the arginase inhibitor BEC and transfection of the antisense (AS) oligonucleotide against arginase I decreased VSMC proliferation and was associated with increased protein content of the cell cycle regulator p21Waf1/Cip1. IL-1β incubation induced inducible nitric oxide synthase (iNOS) mRNA expression and protein levels in a dose-dependent manner, but did not affect arginase I and II expression. Consistent with this data, IL-1β stimulation resulted in increase in NO production that was significantly augmented by arginase inhibition. The specific iNOS inhibitor 1400W abolished IL-1β-mediated NO production and further accentuated IL-1β-stimulated cell proliferation. Incubation with NO donors GSNO and DETA/NO in the presence of IL-1β abolished VSMCs proliferation and increased p21Waf1/Cip1 protein content. Furthermore, incubation with the cGMP analogue 8-Br-cGMP prevented IL-1β-induced VSMCs proliferation. In conclusion, arginase inhibition augmented iNOS-dependent NO production that resulted in suppression of IL-1β-induced VSMCs proliferation in a cGMP-dependent manner.

  6. [Vascular factors in dementia].

    PubMed

    Bidzan, Leszek

    2005-01-01

    Cerebrovascular factors are a common cause of dementia or contribute to cognitive decline in other dementias. Studies showing that cerebrovascular factors are the risk factors for neurodegenerative dementias, especially Alzheimer's disease. Practically all neurodegenerative dementias have a vascular component that reduces cerebral perfusion and has great impact on the clinical picture. Recent data support the view that the neurodegenerative process is caused by cerebrovascular mechanisms. The results showed that patients with vascular cognitive impairment have a typical clinical picture. Various important non-cognitive features are caused by cerebrovascular factors and are associated with a more rapid course of illness. On the other hand the term vascular diseases or cerebrovascular factors include a variety of vascular pathologies. PMID:16358596

  7. Early Detection of Ventilation-Induced Brain Injury Using Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: An In Vivo Study in Preterm Lambs

    PubMed Central

    Skiöld, Béatrice; Wu, Qizhu; Hooper, Stuart B.; Davis, Peter G.; McIntyre, Richard; Tolcos, Mary; Pearson, James; Vreys, Ruth; Egan, Gary F.; Barton, Samantha K.; Cheong, Jeanie L. Y.; Polglase, Graeme R.

    2014-01-01

    Background and Aim High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. Methods Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. Results No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. Conclusion Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is

  8. Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

    PubMed Central

    2011-01-01

    Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI). Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001). Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation. PMID:21486492

  9. Vascular Diseases

    MedlinePlus

    ... heart and blood vessels, such as diabetes or high cholesterol Smoking Obesity Losing weight, eating healthy foods, being active and not smoking can help vascular disease. Other treatments include medicines and surgery.

  10. Assessing vascular dementia.

    PubMed

    Forette, F; Rigaud, A S; Morin, M; Gisselbrecht, M; Bert, P

    1995-10-01

    Vascular dementia is the most common cause of dementia in the elderly after Alzheimer's disease. Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagic dementia. The difficulty of diagnosing vascular dementia must not be underestimated and an international consensus is needed for epidemiological studies. The NINCDS-AIREN group has recently published diagnostic criteria. The State of California Alzheimer's Disease Diagnostic and Treatment Centers also proposed some which differ from the NINCDS-AIREN criteria in considering only ischaemic vascular dementia and not other mechanisms such as haemorrhagic or hypoxic lesions. Most studies stress hypertension as the most powerful risk factor for all forms of vascular dementia. The incidence rate ranges from 7 per 1000 person-years in normal volunteers to 16 per 1000 person-years in hypertensive patients. No therapeutic attempt has influenced the course of the disease once the dementing condition is established. The only effective approach is preventive treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm that the treatment of isolated systolic hypertension is able to reduce its incidence.

  11. [Vascular dementia].

    PubMed

    Peters, N; Dichgans, M

    2010-10-01

    Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.

  12. Lung stress, strain, and energy load: engineering concepts to understand the mechanism of ventilator-induced lung injury (VILI).

    PubMed

    Nieman, Gary F; Satalin, Joshua; Andrews, Penny; Habashi, Nader M; Gatto, Louis A

    2016-12-01

    It was recently shown that acute respiratory distress syndrome (ARDS) mortality has not been reduced in over 15 years and remains ~40 %, even with protective low tidal volume (LVt) ventilation. Thus, there is a critical need to develop novel ventilation strategies that will protect the lung and reduce ARDS mortality. Protti et al. have begun to analyze the impact of mechanical ventilation on lung tissue using engineering methods in normal pigs ventilated for 54 h. They used these methods to assess the impact of a mechanical breath on dynamic and static global lung strain and energy load. Strain is the change in lung volume in response to an applied stress (i.e., Tidal Volume-Vt). This study has yielded a number of exciting new concepts including the following: (1) Individual mechanical breath parameters (e.g., Vt or Plateau Pressure) are not directly correlated with VILI but rather any combination of parameters that subject the lung to excessive dynamic strain and energy/power load will cause VILI; (2) all strain is not equal; dynamic strain resulting in a dynamic energy load (i.e., kinetic energy) is more damaging to lung tissue than static strain and energy load (i.e., potential energy); and (3) a critical consideration is not just the size of the Vt but the size of the lung that is being ventilated by this Vt. This key concept merits attention since our current protective ventilation strategies are fixated on the priority of keeping the Vt low. If the lung is fully inflated, a large Vt is not necessarily injurious. In conclusion, using engineering concepts to analyze the impact of the mechanical breath on the lung is a novel new approach to investigate VILI mechanisms and to help design the optimally protective breath. Data generated using these methods have challenged some of the current dogma surrounding the mechanisms of VILI and of the components in the mechanical breath necessary for lung protection.

  13. Lung stress, strain, and energy load: engineering concepts to understand the mechanism of ventilator-induced lung injury (VILI).

    PubMed

    Nieman, Gary F; Satalin, Joshua; Andrews, Penny; Habashi, Nader M; Gatto, Louis A

    2016-12-01

    It was recently shown that acute respiratory distress syndrome (ARDS) mortality has not been reduced in over 15 years and remains ~40 %, even with protective low tidal volume (LVt) ventilation. Thus, there is a critical need to develop novel ventilation strategies that will protect the lung and reduce ARDS mortality. Protti et al. have begun to analyze the impact of mechanical ventilation on lung tissue using engineering methods in normal pigs ventilated for 54 h. They used these methods to assess the impact of a mechanical breath on dynamic and static global lung strain and energy load. Strain is the change in lung volume in response to an applied stress (i.e., Tidal Volume-Vt). This study has yielded a number of exciting new concepts including the following: (1) Individual mechanical breath parameters (e.g., Vt or Plateau Pressure) are not directly correlated with VILI but rather any combination of parameters that subject the lung to excessive dynamic strain and energy/power load will cause VILI; (2) all strain is not equal; dynamic strain resulting in a dynamic energy load (i.e., kinetic energy) is more damaging to lung tissue than static strain and energy load (i.e., potential energy); and (3) a critical consideration is not just the size of the Vt but the size of the lung that is being ventilated by this Vt. This key concept merits attention since our current protective ventilation strategies are fixated on the priority of keeping the Vt low. If the lung is fully inflated, a large Vt is not necessarily injurious. In conclusion, using engineering concepts to analyze the impact of the mechanical breath on the lung is a novel new approach to investigate VILI mechanisms and to help design the optimally protective breath. Data generated using these methods have challenged some of the current dogma surrounding the mechanisms of VILI and of the components in the mechanical breath necessary for lung protection. PMID:27316442

  14. Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice

    PubMed Central

    Hashizume, Masahiro; Mouner, Marc; Chouteau, Joshua M.; Gorodnya, Olena M.; Ruchko, Mykhaylo V.; Potter, Barry J.; Wilson, Glenn L.; Gillespie, Mark N.

    2013-01-01

    This study tested the hypothesis that oxidative mitochondrial-targeted DNA (mtDNA) damage triggered ventilator-induced lung injury (VILI). Control mice and mice infused with a fusion protein targeting the DNA repair enzyme, 8-oxoguanine-DNA glycosylase 1 (OGG1) to mitochondria were mechanically ventilated with a range of peak inflation pressures (PIP) for specified durations. In minimal VILI (1 h at 40 cmH2O PIP), lung total extravascular albumin space increased 2.8-fold even though neither lung wet/dry (W/D) weight ratios nor bronchoalveolar lavage (BAL) macrophage inflammatory protein (MIP)-2 or IL-6 failed to differ from nonventilated or low PIP controls. This increase in albumin space was attenuated by OGG1. Moderately severe VILI (2 h at 40 cmH2O PIP) produced a 25-fold increase in total extravascular albumin space, a 60% increase in W/D weight ratio and marked increases in BAL MIP-2 and IL-6, accompanied by oxidative mitochondrial DNA damage, as well as decreases in the total tissue glutathione (GSH) and GSH/GSSH ratio compared with nonventilated lungs. All of these injury indices were attenuated in OGG1-treated mice. At the highest level of VILI (2 h at 50 cmH2O PIP), OGG1 failed to protect against massive lung edema and BAL cytokines or against depletion of the tissue GSH pool. Interestingly, whereas untreated mice died before completing the 2-h protocol, OGG1-treated mice lived for the duration of observation. Thus mitochondrially targeted OGG1 prevented VILI over a range of ventilation times and pressures and enhanced survival in the most severely injured group. These findings support the concept that oxidative mtDNA damage caused by high PIP triggers induction of acute lung inflammation and injury. PMID:23241530

  15. Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice.

    PubMed

    Hashizume, Masahiro; Mouner, Marc; Chouteau, Joshua M; Gorodnya, Olena M; Ruchko, Mykhaylo V; Potter, Barry J; Wilson, Glenn L; Gillespie, Mark N; Parker, James C

    2013-02-15

    This study tested the hypothesis that oxidative mitochondrial-targeted DNA (mtDNA) damage triggered ventilator-induced lung injury (VILI). Control mice and mice infused with a fusion protein targeting the DNA repair enzyme, 8-oxoguanine-DNA glycosylase 1 (OGG1) to mitochondria were mechanically ventilated with a range of peak inflation pressures (PIP) for specified durations. In minimal VILI (1 h at 40 cmH(2)O PIP), lung total extravascular albumin space increased 2.8-fold even though neither lung wet/dry (W/D) weight ratios nor bronchoalveolar lavage (BAL) macrophage inflammatory protein (MIP)-2 or IL-6 failed to differ from nonventilated or low PIP controls. This increase in albumin space was attenuated by OGG1. Moderately severe VILI (2 h at 40 cmH(2)O PIP) produced a 25-fold increase in total extravascular albumin space, a 60% increase in W/D weight ratio and marked increases in BAL MIP-2 and IL-6, accompanied by oxidative mitochondrial DNA damage, as well as decreases in the total tissue glutathione (GSH) and GSH/GSSH ratio compared with nonventilated lungs. All of these injury indices were attenuated in OGG1-treated mice. At the highest level of VILI (2 h at 50 cmH(2)O PIP), OGG1 failed to protect against massive lung edema and BAL cytokines or against depletion of the tissue GSH pool. Interestingly, whereas untreated mice died before completing the 2-h protocol, OGG1-treated mice lived for the duration of observation. Thus mitochondrially targeted OGG1 prevented VILI over a range of ventilation times and pressures and enhanced survival in the most severely injured group. These findings support the concept that oxidative mtDNA damage caused by high PIP triggers induction of acute lung inflammation and injury.

  16. Antioxidants and vascular health.

    PubMed

    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.

  17. Vascular emergencies.

    PubMed

    Semashko, D C

    1997-01-01

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

  18. Pravastatin inhibits fibrinogen- and FDP-induced inflammatory response via reducing the production of IL-6, TNF-α and iNOS in vascular smooth muscle cells.

    PubMed

    Lu, Peipei; Liu, Juntian; Pang, Xiaoming

    2015-10-01

    Atherosclerosis is a chronic inflammatory response of the arterial wall to pro‑atherosclerotic factors. As an inflammatory marker, fibrinogen directly participates in the pathogenesis of atherosclerosis. Our previous study demonstrated that fibrinogen and fibrin degradation products (FDP) produce a pro‑inflammatory effect on vascular smooth muscle cells (VSMCs) through inducing the production of interleukin‑6 (IL‑6), tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS). In the present study, the effects of pravastatin on fibrinogen‑ and FDP‑induced expression of IL‑6, TNF‑α and iNOS were observed in VSMCs. The results showed that pravastatin dose‑dependently inhibited fibrinogen‑ and FDP‑stimulated expression of IL‑6, TNF‑α and iNOS in VSMCs at the mRNA and protein level. The maximal inhibition of protein expression of IL‑6, TNF‑α and iNOS was 46.9, 42.7 and 49.2% in fibrinogen‑stimulated VSMCs, and 50.2, 49.8 and 53.6% in FDP‑stimulated VSMCs, respectively. This suggests that pravastatin has the ability to relieve vascular inflammation via inhibiting the generation of IL‑6, TNF‑α and iNOS. The results of the present study may aid in further explaining the beneficial effects of pravastatin on atherosclerosis and related cardiovascular diseases. In addition, they suggest that application of pravastatin may be beneficial for prevention of atherosclerosis formation in hyperfibrinogenemia.

  19. Use of an optical technique to evaluate the cerebral vascular effects of alcohol (A): Effects on deoxyhemoglobin (DH) and levels of reduced cytochrome oxidase (rCO)

    SciTech Connect

    Barbour, R.L.; Gebiewold, A.; Altura, B.M. )

    1992-02-26

    The dose-response effects of acute A infusion were studied to examine the suggestion that A can induce stroke-like events as a consequence of cerebral vasospasm. By employing a single sending and receiving fiber, an optical backscatter measurement was employed to monitor the levels in DH and rCO in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either a bolus infusion (BI) or to a constant infusion (CI) of 5 or 10% A at various rates. Results showed that low BI doses of A typically produced a slight increase in the oxyhemoglobin signal indicating that vasodilation had probably occurred. Higher BI doses, however, produced a prompt and significant reduction in the hemoglobin signal with a rise in rCO suggesting a vasoconstrictor response leading to ischemia, followed by recovery within 3-5 min. CI of A produced a similar cerebral vascular response, in a dose-related manner, but of a more sustained nature. At 30-50% of the BI dose levels, a global blanching of the brain surface occurred; rCO levels increased by 50-90% with a corresponding decline in levels of oxyhemoglobin. Control experiments using identical volumes/flow rates of Ringers solution failed to produce any alterations in the optical spectrum. Overall, these data indicate that, depending on dose, (a) A can induce vasodilatory or vasoconstrictor effects in the intact brain; (b) the more pronounced effects involve vasospasm in the cortical microcirculation leading to global ischemia as determined by elevated levels of rCO and DH; (c) optical measurements permit direct noninvasive assessment of the cerebral vascular effects of substances of abuse.

  20. Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension.

    PubMed

    García-Álvarez, Ana; Pereda, Daniel; García-Lunar, Inés; Sanz-Rosa, David; Fernández-Jiménez, Rodrigo; García-Prieto, Jaime; Nuño-Ayala, Mario; Sierra, Federico; Santiago, Evelyn; Sandoval, Elena; Campelos, Paula; Agüero, Jaume; Pizarro, Gonzalo; Peinado, Víctor I; Fernández-Friera, Leticia; García-Ruiz, José M; Barberá, Joan A; Castellá, Manuel; Sabaté, Manel; Fuster, Valentín; Ibañez, Borja

    2016-07-01

    Beta-3 adrenergic receptor (β3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of β3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of β3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of β3AR mRNA and the vasodilator response of β3AR agonists in pulmonary arteries. Single intravenous administration of the β3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different β3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m(2) for BRL37344 vs. +1.5 for vehicle, p = 0.04; and -1.8 Wood units/m(2) for mirabegron vs. +1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in β3AR agonists-treated pigs. β3AR was expressed in human pulmonary arteries and β3AR agonists produced vasodilatation. β3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.

  1. Vascular calcification: Mechanisms of vascular smooth muscle cell calcification.

    PubMed

    Leopold, Jane A

    2015-05-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk.

  2. Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial).

    PubMed

    Vossen, Liv M; Schurgers, Leon J; van Varik, Bernard J; Kietselaer, Bas L J H; Vermeer, Cees; Meeder, Johannes G; Rahel, Braim M; van Cauteren, Yvonne J M; Hoffland, Ge A; Rennenberg, Roger J M W; Reesink, Koen D; de Leeuw, Peter W; Kroon, Abraham A

    2015-10-28

    Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.

  3. Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial)

    PubMed Central

    Vossen, Liv M.; Schurgers, Leon J.; van Varik, Bernard J.; Kietselaer, Bas L. J. H.; Vermeer, Cees; Meeder, Johannes G.; Rahel, Braim M.; van Cauteren, Yvonne J. M.; Hoffland, Ge A.; Rennenberg, Roger J. M. W.; Reesink, Koen D.; de Leeuw, Peter W.; Kroon, Abraham A.

    2015-01-01

    Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD. PMID:26516910

  4. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

    PubMed

    Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

    2015-04-15

    Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats.

  5. Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR) Is Associated with Activation of the Renin-Angiotensin System (RAS) to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension

    PubMed Central

    Wang, La-mei; Tang, Na; Zhong, Hua; Liu, Yong-min; Li, Zhen; Feng, Qian; He, Fang

    2016-01-01

    The proliferation of vascular smooth muscle cells (VSMCs), remodeling of the vasculature, and the renin-angiotensin system (RAS) play important roles in the development of essential hypertension (EH), which is defined as high blood pressure (BP) in which secondary causes, such as renovascular disease, are absent. The calcium-sensing receptor (CaSR) is involved in the regulation of BP. However, the underlying mechanisms by which the CaSR regulates BP are poorly understood. In the present study, the role of the CaSR in EH was investigated using male spontaneously hypertensive rats (SHRs) and rat and human plasma samples. The percentages of medial wall thickness to external diameter (WT%), total vessel wall cross-sectional area to the total area (WA%) of thoracic arteries, as well as the percentage of wall area occupied by collagen to total vessel wall area (CA%) were determined. Tissue protein expression and plasma concentrations of the CaSR, cyclic adenosine monophosphate (cAMP), renin, and angiotensin II (Ang II) were additionally assessed. WT%, WA%, and CA% were found to increase with increasing BP, whereas the plasma concentration of CaSR was found to decrease. With increasing BP, the levels of smooth muscle actin and calponin decreased, whereas those of osteopontin and proliferating cell nuclear antigen increased. The CaSR level negatively correlated with the levels of cAMP and Ang II, but positively correlated with those of renin. Our data suggest that reduced expression of the CaSR is correlated with activation of the RAS, which induces increased vascular remodeling and VSMC proliferation, and thereby associated with EH in the SHR model and in the Han Chinese population. Our findings provide new insights into the pathogenesis of EH. PMID:27391973

  6. Green Tea Polyphenol Epigallocatechin Gallate Reduces Endothelin-1 Expression and Secretion in Vascular Endothelial Cells: Roles for AMP-Activated Protein Kinase, Akt, and FOXO1

    PubMed Central

    Reiter, Chad E. N.; Kim, Jeong-a; Quon, Michael J.

    2010-01-01

    Epigallocatechin gallate (EGCG), a green tea polyphenol, promotes vasodilation by phosphatidylinositol 3-kinase-dependent activation of Akt and endothelial nitric oxide synthase to stimulate production of nitric oxide. Reduction in endothelin-1 (ET-1) synthesis may also increase bioavailability of nitric oxide. We hypothesized that the phosphatidylinositol 3-kinase-dependent transcription factor FOXO1 may mediate effects of EGCG to regulate expression of ET-1 in endothelial cells. EGCG treatment (10 μm, 8 h) of human aortic endothelial cells reduced expression of ET-1 mRNA, protein, and ET-1 secretion. We identified a putative FOXO binding domain in the human ET-1 promoter 51 bp upstream from the transcription start site. Trans-activation of a human ET-1 (hET-1) promoter luciferase reporter was enhanced by coexpression of a constitutively nuclear FOXO1 mutant, whereas expression of a mutant FOXO1 with disrupted DNA binding domain did not trans-activate the hET-1 promoter. Disrupting the hET-1 putative FOXO binding domain by site-directed mutagenesis ablated promoter activity in response to overexpression of wild-type FOXO1. EGCG stimulated time-dependent phosphorylation of Akt (S473), FOXO1 (at Akt phosphorylation site T24), and AMP-activated protein kinase α (AMPKα) (T172). EGCG-induced nuclear exclusion of FOXO1, FOXO1 binding to the hET-1 promoter, and reduction of ET-1 expression was partially inhibited by the AMPK inhibitor Compound C. Basal ET-1 protein expression was enhanced by short interfering RNA knock-down of Akt and reduced by short interfering RNA knock-down of FOXO1 or adenovirus-mediated expression of dominant-negative Foxo1. We conclude that EGCG decreases ET-1 expression and secretion from endothelial cells, in part, via Akt- and AMPK-stimulated FOXO1 regulation of the ET-1 promoter. These findings may be relevant to beneficial cardiovascular actions of green tea. PMID:19887561

  7. Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients

    SciTech Connect

    Hitomi, Toshiaki; Habu, Toshiyuki; Kobayashi, Hatasu; Okuda, Hiroko; Harada, Kouji H.; Osafune, Kenji; Taura, Daisuke; Sone, Masakatsu; Asaka, Isao; Ameku, Tomonaga; Watanabe, Akira; Kasahara, Tomoko; Sudo, Tomomi; Shiota, Fumihiko; Hashikata, Hirokuni; Takagi, Yasushi; Morito, Daisuke; Miyamoto, Susumu; Nakao, Kazuwa; Koizumi, Akio

    2013-08-16

    Highlights: •Angiogenic activities were reduced in iPSECs from MMD patients. •Many mitosis-regulated genes were downregulated in iPSECs from MMD patients. •RNF213 R4810K downregulated Securin and inhibited angiogenic activity. •Securin suppression by siRNA reduced angiogenic activities of iPSECs and HUVECs. -- Abstract: Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. Induced pluripotent stem cells (iPSCs) were established from unaffected fibroblast donors with wild-type RNF213 alleles, and from carriers/patients with one or two RNF213 R4810K alleles. Angiogenic activities of iPSC-derived vascular endothelial cells (iPSECs) from patients and carriers were lower (49.0 ± 19.4%) than from wild-type subjects (p < 0.01). Gene expression profiles in iPSECs showed that Securin was down-regulated (p < 0.01) in carriers and patients. Overexpression of RNF213 R4810K downregulated Securin, inhibited angiogenic activity (36.0 ± 16.9%) and proliferation of humanumbilical vein endothelial cells (HUVECs) while overexpression of RNF213 wild type did not. Securin expression was downregulated using RNA interference techniques, which reduced the level of tube formation in iPSECs and HUVECs without inhibition of proliferation. RNF213 R4810K reduced angiogenic activities of iPSECs from patients with MMD, suggesting that it is a promising in vitro model for MMD.

  8. Plant Vascular Biology 2013: vascular trafficking.

    PubMed

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä

    2014-04-01

    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland (http://www.pvb2013.org). The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  9. Branding of vascular surgery.

    PubMed

    Perler, Bruce A

    2008-03-01

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

  10. Pulmonary blood volume indexed to lung volume is reduced in newly diagnosed systemic sclerosis compared to normals – a prospective clinical cardiovascular magnetic resonance study addressing pulmonary vascular changes

    PubMed Central

    2013-01-01

    Background Pulmonary involvement, manifested as pulmonary arterial hypertension or pulmonary fibrosis, is the most common cause of death in systemic sclerosis (SSc). We aimed to explore the feasibility of detecting early pulmonary involvement in SSc using recently developed non-invasive quantitative measures of pulmonary physiology using cardiovascular magnetic resonance (CMR). Methods Twenty-seven SSc patients (9 men, 57 ± 13 years) and 10 healthy controls (3 men, 54 ± 9 years) underwent CMR to determine the pulmonary blood volume (PBV) and the PBV variation (PBVV) throughout the cardiac cycle. Patients underwent Doppler echocardiography, high-resolution computed tomography (HRCT), and pulmonary function testing by spirometry. Comparisons were performed using the unpaired t-test and linear regression analysis was performed with Pearson’s correlation coefficient (r). Results Compared to healthy controls, the PBV indexed to lung volume (PBVI) was lower in patients (16 ± 4 vs 20 ± 5%, p < 0.05). There was no difference in PBV (466 ± 87 vs 471 ± 122 mL, p = 0.91) or PBVV/stroke volume (45 ± 10 vs 40 ± 6%, p = 0.09). There were no significant correlations between PBVI and pulmonary artery pressure estimated by Doppler (p = 0.08) the lung’s diffusion capacity for carbon monoxide (DLCO) (p = 0.09), vital capacity (p = 0.45), or pulmonary fibrosis by HRCT (p = 0.74). Conclusions This study is the first to measure the PBV in humans using CMR. Compared to healthy controls, newly diagnosed SSc patients have a reduced amount of blood in the pulmonary vasculature (PBVI) but unchanged pulmonary vascular distensibility (PBVV/stroke volume). PBVI is unrelated to DLCO, pulmonary artery pressure, vital capacity, and the presence of pulmonary fibrosis. PBVI may be a novel parameter reflecting vascular lung involvement in early-stage SSc, and these findings may be consistent with pathophysiological changes of

  11. Collagen vascular disease

    MedlinePlus

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

  12. Angiotensin type 1 receptor blockage reduces l-dopa-induced dyskinesia in the 6-OHDA model of Parkinson's disease. Involvement of vascular endothelial growth factor and interleukin-1β.

    PubMed

    Muñoz, Ana; Garrido-Gil, Pablo; Dominguez-Meijide, Antonio; Labandeira-Garcia, Jose L

    2014-11-01

    Non-neuronal factors such as angiogenesis and neuroinflammation may play a role in l-dopa induced dyskinesias (LID). Vascular endothelial growth factor (VEGF) and proinflammatory cytokines such as interleukin-1β (IL-1β) have been found to be involved in LID. The renin-angiotensin system (RAS) is involved in the inflammatory response and VEGF synthesis via type 1 (AT1) receptors. However, it is not known whether the RAS plays a role in LID and whether AT1 antagonists could constitute a useful therapy against LID. In this study, we investigated whether manipulation of brain RAS is effective in preventing LID. Blocking AT1 receptors with candesartan significantly reduces LID in the 6-OHDA rat model. Chronic dopaminergic denervation induces an increase in striatal levels of VEGF and IL-1β. Dyskinetic animals showed significantly higher levels of VEGF and IL-1β in the lateral striatum and the substantia nigra, as revealed by western blot and real time-PCR analyses. Interestingly, animals treated with both candesartan and l-dopa displayed significantly lower levels of VEGF, IL-1β and dyskinesia than those treated with l-dopa alone. The stimulatory effect of angiotensin II (AII) on VEGF expression was confirmed by the addition of AII to primary mesencephalic cultures and intraventricular administration of AII in rats. The results of the present study reveal for the first time that blockage of AT-1 receptors reduces LID. A candesartan-induced decrease in VEGF and IL-1β may be responsible for the beneficial effects, suggesting the brain RAS as a new target for LID treatment in PD patients. PMID:25160895

  13. Loss of Vascular Endothelial Growth Factor A (VEGFA) Isoforms in the Testes of Male Mice Causes Subfertility, Reduces Sperm Numbers, and Alters Expression of Genes That Regulate Undifferentiated Spermatogonia

    PubMed Central

    Lu, Ningxia; Sargent, Kevin M.; Clopton, Debra T.; Pohlmeier, William E.; Brauer, Vanessa M.; McFee, Renee M.; Weber, John S.; Ferrara, Napoleone; Silversides, David W.

    2013-01-01

    Vascular endothelial growth factor A (VEGFA) isoform treatment has been demonstrated to alter spermatogonial stem cell homeostasis. Therefore, we generated pDmrt1-Cre;Vegfa−/− (knockout, KO) mice by crossing pDmrt1-Cre mice to floxed Vegfa mice to test whether loss of all VEGFA isoforms in Sertoli and germ cells would impair spermatogenesis. When first mated, KO males took 14 days longer to get control females pregnant (P < .02) and tended to take longer for all subsequent parturition intervals (9 days; P < .07). Heterozygous males sired fewer pups per litter (P < .03) and after the first litter took 10 days longer (P < .05) to impregnate females, suggesting a more progressive loss of fertility. Reproductive organs were collected from 6-month-old male mice. There were fewer sperm per tubule in the corpus epididymides (P < .001) and fewer ZBTB16-stained undifferentiated spermatogonia (P < .003) in the testes of KO males. Testicular mRNA abundance for Bcl2 (P < .02), Bcl2:Bax (P < .02), Neurog3 (P < .007), and Ret was greater (P = .0005), tended to be greater for Sin3a and tended to be reduced for total Foxo1 (P < .07) in KO males. Immunofluorescence for CD31 and VE-Cadherin showed no differences in testis vasculature; however, CD31-positive staining was evident in undifferentiated spermatogonia only in KO testes. Therefore, loss of VEGFA isoforms in Sertoli and germ cells alters genes necessary for long-term maintenance of undifferentiated spermatogonia, ultimately reducing sperm numbers and resulting in subfertility. PMID:24169552

  14. Vascular restoration therapy and bioresorbable vascular scaffold

    PubMed Central

    Wang, Yunbing; Zhang, Xingdong

    2014-01-01

    This article describes the evolution of minimally invasive intervention technologies for vascular restoration therapy from early-stage balloon angioplasty in 1970s, metallic bare metal stent and metallic drug-eluting stent technologies in 1990s and 2000s, to bioresorbable vascular scaffold (BVS) technology in large-scale development in recent years. The history, the current stage, the challenges and the future of BVS development are discussed in detail as the best available approach for vascular restoration therapy. The criteria of materials selection, design and processing principles of BVS, and the corresponding clinical trial results are also summarized in this article. PMID:26816624

  15. Initiation of vascular development.

    PubMed

    Ohashi-Ito, Kyoko; Fukuda, Hiroo

    2014-06-01

    The initiation of vascular development occurs during embryogenesis and the development of lateral organs, such as lateral roots and leaves. Understanding the mechanism underlying the initiation of vascular development has been an important goal of plant biologists. Auxin flow is a crucial factor involved in the initiation of vascular development. In addition, recent studies have identified key factors that regulate the establishment of vascular initial cells in embryos and roots. In this review, we summarize the recent findings in this field and discuss the initiation of vascular development.

  16. Mechanisms and Clinical Consequences of Vascular Calcification

    PubMed Central

    Zhu, Dongxing; Mackenzie, Neil C. W.; Farquharson, Colin; MacRae, Vicky E.

    2012-01-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health. PMID:22888324

  17. Imaging Pediatric Vascular Lesions

    PubMed Central

    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

  18. Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury.

    PubMed

    Rizzo, Alicia N; Sammani, Saad; Esquinca, Adilene E; Jacobson, Jeffrey R; Garcia, Joe G N; Letsiou, Eleftheria; Dudek, Steven M

    2015-12-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), an illness characterized by life-threatening vascular leak, is a significant cause of morbidity and mortality in critically ill patients. Recent preclinical studies and clinical observations have suggested a potential role for the chemotherapeutic agent imatinib in restoring vascular integrity. Our prior work demonstrates differential effects of imatinib in mouse models of ALI, namely attenuation of LPS-induced lung injury but exacerbation of ventilator-induced lung injury (VILI). Because of the critical role of mechanical ventilation in the care of patients with ARDS, in the present study we pursued an assessment of the effectiveness of imatinib in a "two-hit" model of ALI caused by combined LPS and VILI. Imatinib significantly decreased bronchoalveolar lavage protein, total cells, neutrophils, and TNF-α levels in mice exposed to LPS plus VILI, indicating that it attenuates ALI in this clinically relevant model. In subsequent experiments focusing on its protective role in LPS-induced lung injury, imatinib attenuated ALI when given 4 h after LPS, suggesting potential therapeutic effectiveness when given after the onset of injury. Mechanistic studies in mouse lung tissue and human lung endothelial cells revealed that imatinib inhibits LPS-induced NF-κB expression and activation. Overall, these results further characterize the therapeutic potential of imatinib against inflammatory vascular leak.

  19. Society for Vascular Medicine

    MedlinePlus

    ... Sessions June 14-17, 2017 Sheraton New Orleans New Orleans, LA USA Board Review Course June 16-18, 2017 SVM in the Vascular Lab June 17, 2017 Learn more Patient Information Pages from Vascular Medicine October 2016 Smoking Cessation More info for patients. SVM Case ...

  20. [Vascular graft prosthesis].

    PubMed

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

    2004-06-01

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

  1. [Vascular factors in glaucoma].

    PubMed

    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.

  2. [Vascular factors in glaucoma].

    PubMed

    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

  3. High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

    PubMed Central

    2011-01-01

    Background To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses. Methods Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured. Results Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed. Conclusions During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators. PMID:22204611

  4. Vascular Access in Children

    SciTech Connect

    Krishnamurthy, Ganesh Keller, Marc S.

    2011-02-15

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the 'expert procedural pyramid' is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

  5. New Approaches for Vascular Anastomoses.

    PubMed

    Bonilla, Luis F.; Sullivan, Daniel J.

    2001-02-01

    Increasing interest in minimally invasive cardiac surgical procedures has generated a renewed interest in facilitated methods to create vascular anastomosis. These devices, in order to be viable, must perform equally or better than sutures. An extensive review of the literature was performed on the different ways to create a mechanical vascular anastomosis. The experience of the authors with the development of a family of connectors (The Symmetry Bypass System; St. Jude Medical, Minneapolis, MN) is presented. The Aortic Connector System (St. Jude Medical) has undergone extensive animal testing with 30-, 90-, and 180-day follow-up. Over 250 human implants have been performed successfully. Preliminary animal studies with the stainless steel coronary connector are also presented. The creation of a facilitated mechanical vascular anastomosis should not compromise quality or patency rates, and produce at least the same results as those obtained with standard suturing techniques. These devices dramatically reduce the time to perform an anastomosis and eliminate the need for aortic clamping and cardiopulmonary bypass. These advantages should result in a significant reduction in surgical complications, and may facilitate a move to true endoscopic and/or percutaneous bypass. PMID:11177719

  6. Vascular ring (image)

    MedlinePlus

    Vascular ring is a term used to describe a number of abnormal formations of the aorta, the large artery ... the pulmonary artery. The abnormal vessel(s) forms a ring, which encircles and may press down on the ...

  7. Heart and vascular services

    MedlinePlus

    ... scan of the heart Stress tests (many different types of stress tests exist) Vascular ultrasound, such as carotid ultrasound Venous ultrasound of the arms and legs SURGERIES AND INTERVENTIONS ... these types of procedures, a catheter is inserted through the ...

  8. Vascular Disease Foundation

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  9. Implications of Vascular Aging

    PubMed Central

    Barodka, Viachaslau M.; Joshi, Brijen L.; Berkowitz, Dan E.; Hogue, Charles W.; Nyhan, Daniel

    2011-01-01

    Chronological age is a well established risk factor for the development of cardiovascular diseases. The changes that accumulate in the vasculature with age, though, are highly variable. It is now increasingly recognized that indices of vascular health are more reliable than age per se in predicting adverse cardiovascular outcomes. The variation in the accrual of these age-related vascular changes is a function of multiple genetic and environmental factors. In this review, we highlight some of the pathophysiological mechanisms that characterize the vascular aging phenotype. Furthermore, we provide an overview of the key outcome studies that address the value of these vascular health indices in general and discuss potential effects on perioperative cardiovascular outcomes. PMID:21474663

  10. Sinuosities in vascular structures

    NASA Astrophysics Data System (ADS)

    Masson, J.-B.; Martin, J.-L.

    2007-12-01

    In most organs, depending on the scale, the nature of the heart pump, the geometry and topology of the organ, some of the blood vessels tend to exhibit sinuous trajectories. We describe a part of this sinuous behavior, including partial biological and strong physical effects in a global physical framework. We will voluntarily focus on physical and topological effects. This study is performed on the vitelline membrane of the chicken embryo. Crossing angles, sinuosity, and the oscillation amplitude of the vascular system are analyzed. Surprisingly, the equation of river meandering dynamics is found to model the sinuosities in the vascular system, and an extension of this equation to non planar case is able to explain the effect of tissue global curvature on the vascular system. Results of this study could lead to a new understanding of the interplay between biological signaling and physical effects in determining the vascular pattern in different tissues.

  11. What Is Vascular Disease?

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  12. Women and Vascular Disease

    MedlinePlus

    ... Search Patient information Membership Directory (SIR login) Interventional Radiology Women and Vascular Disease Early Warning Symptom for ... major public health issue, the Society of Interventional Radiology recommends greater screening efforts by the medical community ...

  13. Vascular structures in dermoscopy*

    PubMed Central

    Ayhan, Erhan; Ucmak, Derya; Akkurt, ZeynepMeltem

    2015-01-01

    Dermoscopy is an aiding method in the visualization of the epidermis and dermis. It is usually used to diagnose melanocytic lesions. In recent years, dermoscopy has increasingly been used to diagnose non-melanocytic lesions. Certain vascular structures, their patterns of arrangement and additional criteria may demonstrate lesion-specific characteristics. In this review, vascular structures and their arrangements are discussed separately in the light of conflicting views and an overview of recent literature. PMID:26375224

  14. Vascular Hyperpermeability and Aging

    PubMed Central

    Oakley, Ryan; Tharakan, Binu

    2014-01-01

    Vascular hyperpermeability, the excessive leakage of fluid and proteins from blood vessels to the interstitial space, commonly occurs in traumatic and ischemic injuries. This hyperpermeability causes tissue vasogenic edema, which often leads to multiple organ failure resulting in patient death. Vascular hyperpermeability occurs most readily in small blood vessels as their more delicate physical constitution makes them an easy target for barrier dysfunction. A single layer of endothelial cells, linked to one another by cell adhesion molecules, covers the interior surface of each blood vessel. The cell adhesion molecules play a key role in maintaining barrier functions like the regulation of permeability. Aging is a major risk factor for microvascular dysfunction and hyperpermeability. Apart from age-related remodeling of the vascular wall, endothelial barrier integrity and function declines with the advancement of age. Studies that address the physiological and molecular basis of vascular permeability regulation in aging are currently very limited. There have been many cellular and molecular mechanisms proposed to explain aging-related endothelial dysfunction but their true relationship to barrier dysfunction and hyperpermeability is not clearly known. Among the several mechanisms that promote vascular dysfunction and hyperpermeability, the following are considered major contributors: oxidative stress, inflammation, and the activation of apoptotic signaling pathways. In this review we highlighted (a) the physiological, cellular and molecular changes that occur in the vascular system as a product of aging; (b) the potential mechanisms by which aging leads to barrier dysfunction and vascular hyperpermeability in the peripheral and the blood-brain barrier; (c) the mechanisms by which the age-related increases in oxidative stress, inflammatory markers and apoptotic signaling etc. cause endothelial dysfunction and their relationship to hyperpermeability; and (d) the

  15. Stroke injury, cognitive impairment and vascular dementia.

    PubMed

    Kalaria, Raj N; Akinyemi, Rufus; Ihara, Masafumi

    2016-05-01

    The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25-30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood-brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

  16. Stroke injury, cognitive impairment and vascular dementia☆

    PubMed Central

    Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

    2016-01-01

    The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

  17. Salt controls endothelial and vascular phenotype.

    PubMed

    Kusche-Vihrog, Kristina; Schmitz, Boris; Brand, Eva

    2015-03-01

    High salt (NaCl) intake promotes the development of vascular diseases independent of a rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. This article summarizes our current understanding of the molecular mechanisms of high salt-induced alterations of the endothelial phenotype, the impact of the individual endothelial genotype, and the overall vascular phenotype. We focus on the endothelial Na(+) channel (EnNaC)-controlled nanomechanical properties of the endothelium, since high Na(+) leads to an EnNaC-induced Na(+)-influx and subsequent stiffening of endothelial cells. The mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function. However, interindividual differences exist in the response to high salt intake which involves different endothelial genotypes. Thus, selected genes and genetic variants contributing to the development of salt-induced endothelial dysfunction and hypertension are discussed. In this review, we focus on the role of salt in endothelial and vascular (dys)function and the link between salt-induced changes of the endothelial and vascular phenotype and its clinical implications.

  18. Exercise, Vascular Stiffness, and Tissue Transglutaminase

    PubMed Central

    Steppan, Jochen; Sikka, Gautam; Jandu, Simran; Barodka, Viachaslau; Halushka, Marc K.; Flavahan, Nicholas A.; Belkin, Alexey M.; Nyhan, Daniel; Butlin, Mark; Avolio, Alberto; Berkowitz, Dan E.; Santhanam, Lakshmi

    2014-01-01

    Background Vascular aging is closely associated with increased vascular stiffness. It has recently been demonstrated that decreased nitric oxide (NO)‐induced S‐nitrosylation of tissue transglutaminase (TG2) contributes to age‐related vascular stiffness. In the current study, we tested the hypothesis that exercise restores NO signaling and attenuates vascular stiffness by decreasing TG2 activity and cross‐linking in an aging rat model. Methods and Results Rats were subjected to 12 weeks of moderate aerobic exercise. Aging was associated with diminished phosphorylated endothelial nitric oxide synthase and phosphorylated vasodilator‐stimulated phosphoprotein abundance, suggesting reduced NO signaling. TG2 cross‐linking activity was significantly increased in old animals, whereas TG2 abundance remained unchanged. These alterations were attenuated in the exercise cohort. Simultaneous measurement of blood pressure and pulse wave velocity (PWV) demonstrated increased aortic stiffness in old rats, compared to young, at all values of mean arterial pressure (MAP). The PWV‐MAP correlation in the old sedentary and old exercise cohorts was similar. Tensile testing of the vessels showed increased stiffness of the aorta in the old phenotype with a modest restoration of mechanical properties toward the young phenotype with exercise. Conclusions Increased vascular stiffness during aging is associated with decreased TG2 S‐nitrosylation, increased TG2 cross‐linking activity, and increased vascular stiffness likely the result of decreased NO bioavailability. In this study, a brief period of moderate aerobic exercise enhanced NO signaling, attenuated TG cross‐linking activity, and reduced ex vivo tensile properties, but failed to reverse functional vascular stiffness in vivo, as measured by PWV. PMID:24721796

  19. Vascular Integrity in the Pathogenesis of Brain Arteriovenous Malformation

    PubMed Central

    Zhang, Rui; Zhu, Wan

    2015-01-01

    Brain arteriovenous malformation (bAVM) is an important cause of intracranial hemorrhage (ICH), particularly in the young population. ICH is the first clinical symptom in about 50 % of bAVM patients. The vessels in bAVM are fragile and prone to rupture, causing bleeding into the brain. About 30 % of unruptured and non-hemorrhagic bAVMs demonstrate microscopic evidence of hemosiderin in the vascular wall. In bAVM mouse models, vascular mural cell coverage is reduced in the AVM lesion, accompanied by vascular leakage and microhemorrhage. In this review, we discuss possible signaling pathways involved in abnormal vascular development in bAVM. PMID:26463919

  20. Smoking and vascular risk: are all forms of smoking harmful to all types of vascular disease?

    PubMed

    Katsiki, N; Papadopoulou, S K; Fachantidou, A I; Mikhailidis, D P

    2013-05-01

    Smoking, both active and passive, is an established vascular risk factor. The present narrative review considers the effects of different forms of smoking (i.e. cannabis, cigar, pipe, smokeless tobacco and cigarette) on cardiovascular risk. Furthermore, the impact of smoking on several vascular risk factors [e.g. hypertension, diabetes mellitus (DM), dyslipidaemia and haemostasis] and on vascular diseases such as coronary heart disease (CHD), peripheral arterial disease (PAD), abdominal aortic aneurysms (AAA) and carotid arterial disease, is discussed. The adverse effects of all forms of smoking and the interactions between smoking and established vascular risk factors highlight the importance of smoking cessation in high-risk patients in terms of both primary and secondary vascular disease prevention. Healthcare providers should discourage people (especially the young) from becoming smokers, strongly encourage all vascular patients to stop smoking and support those who decide to quit by pharmaceutical and psychological interventions. In high-risk populations such as patients with CHD, DM and/or PAD, smoking cessation should always be a part of a multifactorial treatment to reduce vascular risk. PMID:23453194

  1. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  2. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  3. Building Vascular Networks

    PubMed Central

    Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali

    2013-01-01

    Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology. PMID:23152325

  4. Effects of vascularization on cancer nanochemotherapy outcomes

    NASA Astrophysics Data System (ADS)

    Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

    2016-08-01

    Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

  5. Advanced noninvasive imaging of spinal vascular malformations

    PubMed Central

    Eddleman, Christopher S.; Jeong, Hyun; Cashen, Ty A.; Walker, Matthew; Bendok, Bernard R.; Batjer, H. Hunt; Carroll, Timothy J.

    2010-01-01

    Spinal vascular malformations (SVMs) are an uncommon, heterogeneous group of vascular anomalies that can render devastating neurological consequences if they are not diagnosed and treated in a timely fashion. Imaging SVMs has always presented a formidable challenge because their clinical and imaging presentations resemble those of neoplasms, demyelination diseases, and infection. Advancements in noninvasive imaging modalities (MR and CT angiography) have increased during the last decade and have improved the ability to accurately diagnose spinal vascular anomalies. In addition, intraoperative imaging techniques have been developed that aid in the intraoperative assessment before, during, and after resection of these lesions with minimal and/or optimal use of spinal digital subtraction angiography. In this report, the authors review recent advancements in the imaging of SVMs that will likely lead to more timely diagnoses and treatment while reducing procedural risk exposure to the patients who harbor these uncommon spinal lesions. PMID:19119895

  6. Vascular Permeability and Drug Delivery in Cancers

    PubMed Central

    Azzi, Sandy; Hebda, Jagoda K.; Gavard, Julie

    2013-01-01

    The endothelial barrier strictly maintains vascular and tissue homeostasis, and therefore modulates many physiological processes such as angiogenesis, immune responses, and dynamic exchanges throughout organs. Consequently, alteration of this finely tuned function may have devastating consequences for the organism. This is particularly obvious in cancers, where a disorganized and leaky blood vessel network irrigates solid tumors. In this context, vascular permeability drives tumor-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration, and tumor cell extravasation. This can directly restrain the efficacy of conventional therapies by limiting intravenous drug delivery. Indeed, for more effective anti-angiogenic therapies, it is now accepted that not only should excessive angiogenesis be alleviated, but also that the tumor vasculature needs to be normalized. Recovery of normal state vasculature requires diminishing hyperpermeability, increasing pericyte coverage, and restoring the basement membrane, to subsequently reduce hypoxia, and interstitial fluid pressure. In this review, we will introduce how vascular permeability accompanies tumor progression and, as a collateral damage, impacts on efficient drug delivery. The molecular mechanisms involved in tumor-driven vascular permeability will next be detailed, with a particular focus on the main factors produced by tumor cells, especially the emblematic vascular endothelial growth factor. Finally, new perspectives in cancer therapy will be presented, centered on the use of anti-permeability factors and normalization agents. PMID:23967403

  7. Motor cortex excitability in vascular depression.

    PubMed

    Bella, Rita; Ferri, Raffaele; Cantone, Mariagiovanna; Pennisi, Manuela; Lanza, Giuseppe; Malaguarnera, Giulia; Spampinato, Concetto; Giordano, Daniela; Raggi, Alberto; Pennisi, Giovanni

    2011-12-01

    The aim of this study was to evaluate excitatory/inhibitory intracortical circuit changes in patients with vascular depression, and whether there are any interhemispheric differences of motor cortical excitability. Fifteen vascular depressed elderly (VD), ten nondepressed subcortical vascular disease patients (SVD) and ten age-matched controls underwent bilateral motor threshold and paired-pulse studies. They were also assessed for their brain vascular burden at MRI and neuropsychological profile. Executive dysfunction and apathy were significantly higher in VD; we were unable to find significant differences in resting motor threshold, cortical silent period and paired-pulse curves between VD, SVD and controls, and between the two hemispheres in the VD group. Our findings might suggest that neurophysiological mechanisms underlying VD differ from those previously reported in Major Depression (reduced excitability in the left hemisphere) and seem to be similar to those of patients with SVD. Our findings also, support the "vascular depression" hypothesis, suggesting that in VD patients the depressive syndrome is not the primary disease but can be considered as one of the clinical manifestations in the wide symptom spectrum of the cerebral small vessel disease.

  8. Vascular wall extracellular matrix proteins and vascular diseases

    PubMed Central

    Xu, Junyan; Shi, Guo-Ping

    2014-01-01

    Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension. PMID:25045854

  9. Vascular air embolism

    PubMed Central

    Gordy, Stephanie; Rowell, Susan

    2013-01-01

    Vascular air embolism is a rare but potentially fatal event. It may occur in a variety of procedures and surgeries but is most often associated as an iatrogenic complication of central line catheter insertion. This article reviews the incidence, pathophysiology, diagnosis, treatment, and prevention of this phenomenon. PMID:23724390

  10. Adhesion in vascular biology

    PubMed Central

    de Rooij, Johan

    2014-01-01

    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is called transmigration. The endothelial cell layer that forms the inner lining of the vasculature is crucial for the vascular barrier function as well as the regulation of transmigration. Therefore, adhesions between vascular endothelial cells are both tight and dynamic and the mechanisms by which they are established, and the mechanisms by which they are controlled have been extensively studied over the past decades. Because of our fundamental strive to understand biology, but also because defects in vascular barrier control cause a variety of clinical problems and treatment strategies may evolve from our detailed understanding of its mechanisms. This special focus issue features a collection of articles that review key components of the development and control of the endothelial cell-cell junction that is central to endothelial barrier function. PMID:25422845

  11. Engineered Vascularized Muscle Flap.

    PubMed

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

    2016-01-01

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

  12. Advances in Vascular Hyporeactivity After Shock: The Mechanisms and Managements.

    PubMed

    Duan, Chenyang; Yang, Guangming; Li, Tao; Liu, Liangming

    2015-12-01

    Vascular reactivity to vasoconstrictors and vasodilators is greatly reduced after severe trauma, shock, and sepsis or multiple organ dysfunction syndrome. This reduced vascular reactivity severely interferes with the treatment of shock and other critical conditions. In particular, it interferes with the efficacy of vasoactive agents. Consequently, it is very important to elucidate the mechanisms and search for the effective treatment measures. In recent years, a lot of studies focused on the characteristics and the change rules of vascular hyporeactivity and mechanisms following shock. Also, the treatment approaches based on various mechanisms have been a hot pot these years.

  13. Leaf hydraulics II: vascularized tissues.

    PubMed

    Rockwell, Fulton E; Holbrook, N Michele; Stroock, Abraham D

    2014-01-01

    Current models of leaf hydration employ an Ohm's law analogy of the leaf as an ideal capacitor, neglecting the resistance to flow between cells, or treat the leaf as a plane sheet with a source of water at fixed potential filling the mid-plane, neglecting the discrete placement of veins as well as their resistance. We develop a model of leaf hydration that considers the average conductance of the vascular network to a representative areole (region bounded by the vascular network), and represent the volume of tissue within the areole as a poroelastic composite of cells and air spaces. Solutions to the 3D flow problem are found by numerical simulation, and these results are then compared to 1D models with exact solutions for a range of leaf geometries, based on a survey of temperate woody plants. We then show that the hydration times given by these solutions are well approximated by a sum of the ideal capacitor and plane sheet times, representing the time for transport through the vasculature and tissue respectively. We then develop scaling factors relating this approximate solution to the 3D model, and examine the dependence of these scaling factors on leaf geometry. Finally, we apply a similar strategy to reduce the dimensions of the steady state problem, in the context of peristomatal transpiration, and consider the relation of transpirational gradients to equilibrium leaf water potential measurements.

  14. Vascular Anomalies and Airway Concerns

    PubMed Central

    Clarke, Caroline; Lee, Edward I.; Edmonds, Joseph

    2014-01-01

    Vascular anomalies, both tumors and malformations, can occur anywhere in the body, including the airway, often without any external manifestations. However, vascular anomalies involving the airway deserve special consideration as proper recognition and management can be lifesaving. In this article, the authors discuss vascular anomalies as they pertains to the airway, focusing on proper diagnosis, diagnostic modalities, and therapeutic options. PMID:25045336

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

    PubMed Central

    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 of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  16. Vascular cognitive impairment and dementia.

    PubMed

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

    2016-05-01

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

  17. Neurobiology of Vascular Dementia

    PubMed Central

    Enciu, Ana-Maria; Constantinescu, Stefan N.; Popescu, Laurenţiu M.; Mureşanu, Dafin F.; Popescu, Bogdan O.

    2011-01-01

    Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach. PMID:21876809

  18. Plant Vascular Biology 2010

    SciTech Connect

    Ding, Biao

    2014-11-17

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

  19. [Vascular variability syndromes].

    PubMed

    Otsuka, Kuniaki; Okajima, Kiyotaka; Yamanaka, Takashi; Cornelissen, Germaine

    2014-08-01

    Analytical global and local methods applied to human blood pressure (BP) records of around-the-clock measurements. The chronobiological interpretation of ambulatory BP monitoring records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability disorders (VVDs) for an assessment of cardio-, cerebro-, and renovascular disease risk. VVD includes circadian BP over-swinging (CHAT, short for circadian hyper-amplitude tension), deficient heart rate variability, MESOR (midline-estimating statistic of rhythm) hypertension, excessively elevated pulse pressure over 60 mmHg, BP ecphasia (an odd timing of the circadian rhythms in BP but not in that of heart rate) and frequency alteration. The term MESOR-hypertension indicates only one of several VVDs that can combine to for sets of 2, 3 and n-component vascular variability syndromes. PMID:25167758

  20. [Vascular endothelial Barrier Function].

    PubMed

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

    2015-01-01

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

  1. Vascular Cambium Development

    PubMed Central

    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

  2. Congenital Vascular Anomalies.

    PubMed

    Gravereaux, Edwin C.; Nguyen, Louis L.; Cunningham, Leslie D.

    2004-04-01

    Congenital vascular anomalies are rare. The cardiovascular specialist should nevertheless be aware of the more common types of vascular anomalies and understand the implications for patient treatment and the likelihood of associated morbidity. The presentation of congenital arteriovenous malformations can range from asymptomatic or cosmetic lesions, to those causing ischemia, ulceration, hemorrhage, or high-output congestive heart failure. Treatment of large, symptomatic arteriovenous malformations often requires catheter-directed embolization prior to the attempt at complete surgical excision. Later recurrence, due to collateral recruitment, is frequent. Graded compression stockings and leg elevation are the mainstays of treatment for the predominantly venous congenital vascular anomalies. Most congenital central venous disorders are clinically silent. An exception is the retrocaval ureter. Retroaortic left renal vein, circumaortic venous ring, and absent, left-sided or duplicated inferior vena cava are relevant when aortic or inferior vena cava procedures are planned. The treatment of the venous disorders is directed at prevention or management of symptoms. Persistent sciatic artery, popliteal entrapment syndrome, and aberrant right subclavian artery origin are congenital anomalies that are typically symptomatic at presentation. Because they mimic more common diseases, diagnosis is frequently delayed. Delay can result in significant morbidity for the patient. Failure to make the diagnosis of persistent sciatic artery and popliteal entrapment can result in critical limb ischemia and subsequent amputation. Unrecognized aberrant right subclavian artery origin associated with aneurysmal degeneration can rupture and result in death. The treatment options for large-vessel arterial anomalies are surgical, sometimes in combination with endovascular techniques.

  3. Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

    PubMed

    Ma, Yun-Yun; Sun, Lin; Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

    2016-01-01

    Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

  4. Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells

    PubMed Central

    Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

    2016-01-01

    Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

  5. Delivery of Polymeric Nanoparticles to Target Vascular Diseases

    PubMed Central

    Agyare, Edward; Kandimalla, Karunyna

    2015-01-01

    Current advances in nanotechnology have paved the way for the early detection, prevention and treatment of various diseases such as vascular disorders and cancer. These advances have provided novel approaches or modalities of incorporating or adsorbing therapeutic, biosensor and targeting agents into/on nanoparticles. With significant progress, nanomedicine for vascular therapy has shown significant advantages over traditional medicine because of its ability to selectively target the disease site and reduce adverse side effects. Targeted delivery of nanoparticles to vascular endothelial cells or the vascular wall provides an effective and more efficient way for early detection and/or treatment of vascular diseases such as atherosclerosis, thrombosis and Cerebrovascular Amyloid Angiopathy (CAA). Clinical applications of biocompatible and biodegradable polymers in areas such as vascular graft, implantable drug delivery, stent devices and tissue engineering scaffolds have advanced the candidature of polymers as potential nano-carriers for vascular-targeted delivery of diagnostic agents and drugs. This review focuses on the basic aspects of the vasculature and its associated diseases and relates them to polymeric nanoparticle-based strategies for targeting therapeutic agents to diseased vascular site. PMID:26069867

  6. An integrated approach for vascular health: a call to action.

    PubMed

    O'Neill, Blair J; Rana, Shadab N; Bowman, Vincent

    2015-01-01

    Vascular diseases such as stroke, myocardial infarction, most causes of heart failure, dementia, peripheral arterial disease, certain kidney, and many lung and eye conditions are a result of disorders in the blood vessels (large and small) throughout the entire human body. Vascular diseases are the leading cause of preventable death and disability in Canada. Most vascular diseases share common risk factors (high blood pressure, diabetes, dyslipidemia, and obesity), which can be influenced by modifiable health behaviours such as unhealthy diet, smoking, lack of physical activity, and stress. Ninety percent of Canadians face an increased risk, which could be modified by managing these health behaviours and risk factors. Canada's aging population, combined with alarming trends in obesity, physical inactivity, high blood pressure, and diabetes are expected to further increase the social and economic effect of vascular diseases in the coming decades, unless there are major changes in health policy. Even more concerning is the increase in vascular risk factors among Canada's youth, and ethnically diverse populations. Vascular diseases affect not only the patient, but also place burdens on their spouses, families, friends, and communities. Tremendous potential exists to reduce the effects of vascular diseases through healthy public policy, supporting Canadians to make healthy lifestyle changes, and coordinating efforts across the continuum of care in a patient-focused manner. Vascular health requires partnerships for action across many sectors including government, health care practitioners, academia, not-for-profit organizations, and the private sector. The health sector alone cannot solve this problem. PMID:25547559

  7. Double-filter identification of vascular-expressed genes using Arabidopsis plants with vascular hypertrophy and hypotrophy.

    PubMed

    Ckurshumova, Wenzislava; Scarpella, Enrico; Goldstein, Rochelle S; Berleth, Thomas

    2011-08-01

    Genes expressed in vascular tissues have been identified by several strategies, usually with a focus on mature vascular cells. In this study, we explored the possibility of using two opposite types of altered tissue compositions in combination with a double-filter selection to identify genes with a high probability of vascular expression in early organ primordia. Specifically, we generated full-transcriptome microarray profiles of plants with (a) genetically strongly reduced and (b) pharmacologically vastly increased vascular tissues and identified a reproducible cohort of 158 transcripts that fulfilled the dual requirement of being underrepresented in (a) and overrepresented in (b). In order to assess the predictive value of our identification scheme for vascular gene expression, we determined the expression patterns of genes in two unbiased subsamples. First, we assessed the expression patterns of all twenty annotated transcription factor genes from the cohort of 158 genes and found that seventeen of the twenty genes were preferentially expressed in leaf vascular cells. Remarkably, fifteen of these seventeen vascular genes were clearly expressed already very early in leaf vein development. Twelve genes with published leaf expression patterns served as a second subsample to monitor the representation of vascular genes in our cohort. Of those twelve genes, eleven were preferentially expressed in leaf vascular tissues. Based on these results we propose that our compendium of 158 genes represents a sample that is highly enriched for genes expressed in vascular tissues and that our approach is particularly suited to detect genes expressed in vascular cell lineages at early stages of their inception.

  8. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  9. Nanoengineering of therapeutics for retinal vascular disease.

    PubMed

    Gahlaut, Nivriti; Suarez, Sandra; Uddin, Md Imam; Gordon, Andrew Y; Evans, Stephanie M; Jayagopal, Ashwath

    2015-09-01

    Retinal vascular diseases, including diabetic retinopathy, neovascular age related macular degeneration, and retinal vein occlusion, are leading causes of blindness in the Western world. These diseases share several common disease mechanisms, including vascular endothelial growth factor (VEGF) signaling, hypoxia, and inflammation, which provide opportunities for common therapeutic strategies. Treatment of these diseases using laser therapy, anti-VEGF injections, and/or steroids has significantly improved clinical outcomes. However, these strategies do not address the underlying root causes of pathology, and may have deleterious side effects. Furthermore, many patients continue to progress toward legal blindness despite receiving regular therapy. Nanomedicine, the engineering of therapeutics at the 1-100 nm scale, is a promising approach for improving clinical management of retinal vascular diseases. Nanomedicine-based technologies have the potential to revolutionize the treatment of ophthalmology, through enabling sustained release of drugs over several months, reducing side effects due to specific targeting of dysfunctional cells, and interfacing with currently "undruggable" targets. We will discuss emerging nanomedicine-based applications for the treatment of complications associated with retinal vascular diseases, including angiogenesis and inflammation.

  10. The heart and vascular system in dialysis.

    PubMed

    Wanner, Christoph; Amann, Kerstin; Shoji, Tetsuo

    2016-07-16

    The heart and the vascular tree undergo major structural and functional changes when kidney function declines and renal replacement therapy is required. The many cardiovascular risk factors and adaptive changes the heart undergoes include left ventricular hypertrophy and dilatation with concomitant systolic and diastolic dysfunction. Myocardial fibrosis is the consequence of impaired angio-adaptation, reduced capillary angiogenesis, myocyte-capillary mismatch, and myocardial micro-arteriopathy. The vascular tree can be affected by both atherosclerosis and arteriosclerosis with both lipid rich plaques and abundant media calcification. Development of cardiac and vascular disease is rapid, especially in young patients, and the phenotype resembles all aspects of an accelerated ageing process and latent cardiac failure. The major cause of left ventricular hypertrophy and failure and the most common problem directly affecting myocardial function is fluid overload and, usually, hypertension. In situations of stress, such as intradialytic hypotension and hypoxaemia, the hearts of these patients are more vulnerable to developing cardiac arrest, especially when such episodes occur frequently. As a result, cardiac and vascular mortality are several times higher in dialysis patients than in the general population. Trials investigating one pharmacological intervention (eg, statins) have shown limitations. Pragmatic designs for large trials on cardio-active interventions are mandatory for adequate cardioprotective renal replacement therapy. PMID:27226133

  11. Vascular effects of flavonoids.

    PubMed

    Almeida Rezende, Bruno; Pereira, Aline Carvalho; Cortes, Steyner F; Lemos, Virginia Soares

    2016-01-01

    Flavonoids are natural plant-derived polyphenolic compounds with various biological properties particularly in the cardiovascular system, including antiatherogenic, antioxidant, vasodilation, antihypertensive, and antiplatelet activities. These biological properties have been evaluated in several experimental and clinical studies. In addition, extensive reviews have discussed the antiatherogenic effect of these polyphenols. However, limited studies have investigated the potential therapeutic vascular effects of these compounds. This review brings together some recent studies, to establish the different signaling pathways involved in the molecular mechanisms that underlie the vasodilation induced by flavonoids.

  12. Medical management of vascular anomalies.

    PubMed

    Trenor, Cameron C

    2016-03-01

    We have entered an exciting era in the care of patients with vascular anomalies. These disorders require multidisciplinary care and coordination and dedicated centers have emerged to address this need. Vascular tumors have been treated with medical therapies for many years, while malformations have been historically treated with endovascular and operative procedures. The recent serendipitous discoveries of propranolol and sirolimus for vascular anomalies have revolutionized this field. In particular, sirolimus responses are challenging the dogma that vascular malformations are not biologically active. While initially explored for lymphatic anomalies, sirolimus is now being used broadly throughout the spectrum of vascular anomalies. Whether medical therapies are reserved for refractory patients or used first line is currently dependent on the experience and availability of alternative therapies at each institution. On the horizon, we anticipate new drugs targeting genes and pathways involved in vascular anomalies to be developed. Also, combinations of medications and protocols combining medical and procedural approaches are in development for refractory patients. PMID:27607327

  13. The pathobiology of vascular dementia

    PubMed Central

    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 signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

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

    NASA Astrophysics Data System (ADS)

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

    2007-11-01

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

  15. Vascular pattern formation in plants.

    PubMed

    Scarpella, Enrico; Helariutta, Ykä

    2010-01-01

    Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns.

  16. Vascular trauma in civilian practice.

    PubMed Central

    Golledge, J.; Scriven, M. W.; Fligelstone, L. J.; Lane, I. F.

    1995-01-01

    Vascular trauma is associated with major morbidity and mortality, but little is known about its incidence or nature in Britain. A retrospective study of 36 patients requiring operative intervention for vascular trauma under one vascular surgeon over a 6-year period was undertaken. Twenty-four patients suffered iatrogenic trauma (median age 61 years); including cardiological intervention (19), radiological intervention (2), varicose vein surgery (1), umbilical vein catherisation (1) and isolated hyperthermic limb perfusion (1). There were 23 arterial and three venous injuries. Twelve patients had accidental trauma (median age 23 years). Three of the ten patients with blunt trauma were referred for vascular assessment before orthopaedic intervention, two after an on-table angiogram and five only after an initial orthopaedic procedure (range of delay 6 h to 10 days). Injuries were arterial in nine, venous in two and combined in one. Angiography was obtained in six patients, and in two patients with multiple upper limb fractures identified the site of injury when clinical localisation was difficult. A variety of vascular techniques were used to treat the injuries. Two patients died postoperatively and one underwent major limb amputation. Thirty-two (89%) remain free of vascular sequelae after a median follow-up of 48 months (range 3-72 months). Vascular trauma is uncommon in the United Kingdom. To repair the injuries a limited repertoire of vascular surgery techniques is needed. Therefore, vascular surgical assessment should be sought at an early stage to prevent major limb loss. PMID:8540659

  17. Vascularization of engineered teeth.

    PubMed

    Nait Lechguer, A; Kuchler-Bopp, S; Hu, B; Haïkel, Y; Lesot, H

    2008-12-01

    The implantation of cultured dental cell-cell re-associations allows for the reproduction of fully formed teeth, crown morphogenesis, epithelial histogenesis, mineralized dentin and enamel deposition, and root-periodontium development. Since vascularization is critical for organogenesis and tissue engineering, this work aimed to study: (a) blood vessel formation during tooth development, (b) the fate of blood vessels in cultured teeth and re-associations, and (c) vascularization after in vivo implantation. Ex vivo, blood vessels developed in the dental mesenchyme from the cap to bell stages and in the enamel organ, shortly before ameloblast differentiation. In cultured teeth and re-associations, blood-vessel-like structures remained in the peridental mesenchyme, but never developed into dental tissues. After implantation, both teeth and re-associations became revascularized, although later in the case of the re-associations. In implanted re-associations, newly formed blood vessels originated from the host, allowing for their survival, and affording conditions organ growth, mineralization, and enamel secretion.

  18. Vascular Distribution of Nanomaterials

    PubMed Central

    Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

    2014-01-01

    Once considered primarily occupational, novel nanotechnology innovation and application has led to widespread domestic use and intentional biomedical exposures. With these exciting advances, the breadth and depth of toxicological considerations must also be expanded. The vascular system interacts with every tissue in the body, striving to homeostasis. Engineered nanomaterials (ENM) have been reported to distribute in many different organs and tissues. However, these observations have tended to use approaches requiring tissue homogenization and/or gross organ analyses. These techniques, while effective in establishing presence, preclude an exact determination of where ENM are deposited within a tissue. It is necessary to identify this exact distribution and deposition of ENM throughout the cardiovascular system, with respect to vascular hemodynamics and in vivo/ in vitro ENM modifications taken into account if nanotechnology is to achieve its full potential. Distinct levels of the vasculature will first be described as individual compartments. Then the vasculature will be considered as a whole. These unique compartments and biophysical conditions will be discussed in terms of their propensity to favor ENM deposition. Understanding levels of the vasculature will also be discussed. Ultimately, future studies must verify the mechanisms speculated on and presented herein. PMID:24777845

  19. Vascular graft infections.

    PubMed

    Hasse, Barbara; Husmann, Lars; Zinkernagel, Annelies; Weber, Rainer; Lachat, Mario; Mayer, Dieter

    2013-01-01

    Vascular procedures are rarely complicated by infection, but if prosthetic vascular graft infection (PVGI) occurs, morbidity and mortality are high. Several patient-related, surgery-related and postoperative risk factors are reported, but they are not well validated. PVGI is due to bacterial colonisation of the wound and the underlying prosthetic graft, generally as a result of direct contamination during the operative procedure, mainly from the patient's skin or adjacent bowel. There is no consensus on diagnostic criteria or on the best management of PVGI. On the basis of reported clinical studies and our own experience, we advocate a surgical approach combining repeated radical local debridement, with graft preservation whenever possible or partial excision of the infected graft, depending on its condition, plus simultaneous negative-pressure wound therapy (NPWT). In addition, antimicrobial therapy is recommended, but there is no consensus on which classes of agent are adequate for the treatment of PVGI and whether certain infections may be treated by means of NPWT alone. Since staphylococci and Gram-negative rods are likely to be isolated, empirical treatment might include a penicillinase-resistant beta-lactam or a glycopeptide, plus an aminoglycoside, the latter for Gram-negative coverage and synergistic treatment of Gram-positive cocci. Additionally, empirical treatment might include rifampicin since it penetrates well into biofilms.

  20. 219 vascular fellows' perception of the future of vascular surgery.

    PubMed

    Hingorani, Anil P; Ascher, Enrico; Marks, Natalie; Shiferson, Alexander; Puggioni, Alessandra; Tran, Victor; Patel, Nirav; Jacob, Theresa

    2009-01-01

    In an attempt to identify the fellows' concerns about the future of the field of vascular surgery, we conducted a survey consisting of 22 questions at an annual national meeting in March from 2004 to 2007. In order to obtain accurate data, all surveys were kept anonymous. The fellows were asked (1) what type of practice they anticipated they would be in, (2) what the new training paradigm for fellows should be, (3) to assess their expectation of the needed manpower with respect to the demand for vascular surgeons, (4) what were major threats to the future of vascular surgery, (5) whether they had heard of and were in favor of the American Board of Vascular Surgery (ABVS), (6) who should be able to obtain vascular privileges, and (7) about their interest in an association for vascular surgical trainees. Of 273 attendees, 219 (80%) completed the survey. Males made up 87% of those surveyed, and 60% were between the ages of 31 and 35 years. Second-year fellows made up 82% of those surveyed. Those expecting to join a private, academic, or mixed practice made up 35%, 28%, and 20% of the respondents, respectively, with 71% anticipating entering a 100% vascular practice. Forty percent felt that 5 years of general surgery with 2 years of vascular surgery should be the training paradigm, while 45% suggested 3 and 3 years, respectively. A majority, 79%, felt that future demand would exceed the available manpower, while 17% suggested that manpower would meet demand. The major challenges to the future of vascular surgery were felt to be competition from cardiology (82%) or radiology (30%) and lack of an independent board (29%). Seventeen percent were not aware of the ABVS, and only 2% were against it; 71% suggested that vascular privileges be restricted to board-certified vascular surgeons. Seventy-six percent were interested in forming an association for vascular trainees to address the issues of the future job market (67%), endovascular training during fellowship (56

  1. Development of a clinical prediction rule to improve peripheral intravenous cannulae first attempt success in the emergency department and reduce post insertion failure rates: the Vascular Access Decisions in the Emergency Room (VADER) study protocol

    PubMed Central

    Carr, Peter J; Rippey, James C R; Cooke, Marie L; Bharat, Chrianna; Murray, Kevin; Higgins, Niall S; Foale, Aileen; Rickard, Claire M

    2016-01-01

    Introduction Peripheral intravenous cannula (PIVC) insertion is one of the most common clinical interventions performed in emergency care worldwide. However, factors associated with successful PIVC placement and maintenance are not well understood. This study seeks to determine the predictors of first time PIVC insertion success in emergency department (ED) and identify the rationale for removal of the ED inserted PIVC in patients admitted to the hospital ward. Reducing failed insertion attempts and improving peripheral intravenous cannulation practice could lead to better staff and patient experiences, as well as improving hospital efficiency. Methods and analysis We propose an observational cohort study of PIVC insertions in a patient population presenting to ED, with follow-up observation of the PIVC in subsequent admissions to the hospital ward. We will collect specific PIVC observational data such as; clinician factors, patient factors, device information and clinical practice variables. Trained researchers will gather ED PIVC insertion data to identify predictors of insertion success. In those admitted from the ED, we will determine the dwell time of the ED-inserted PIVC. Multivariate regression analyses will be used to identify factors associated with insertions success and PIVC failure and standard statistical validation techniques will be used to create and assess the effectiveness of a clinical predication rule. Ethics and dissemination The findings of our study will provide new evidence to improve insertion success rates in the ED setting and identify strategies to reduce premature device failure for patients admitted to hospital wards. Results will unravel a complexity of factors that contribute to unsuccessful PIVC attempts such as patient and clinician factors along with the products, technologies and infusates used. Trial registration number ACTRN12615000588594; Pre-results. PMID:26868942

  2. Interactive effects of vascular risk burden and advanced age on cerebral blood flow

    PubMed Central

    Bangen, Katherine J.; Nation, Daniel A.; Clark, Lindsay R.; Harmell, Alexandrea L.; Wierenga, Christina E.; Dev, Sheena I.; Delano-Wood, Lisa; Zlatar, Zvinka Z.; Salmon, David P.; Liu, Thomas T.; Bondi, Mark W.

    2014-01-01

    Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines. PMID:25071567

  3. Rodent Models of Vascular Cognitive Impairment.

    PubMed

    Yang, Yi; Kimura-Ohba, Shihoko; Thompson, Jeffrey; Rosenberg, Gary A

    2016-10-01

    Vascular cognitive impairment dementia (VCID), which is an increasingly important cause of dementia in the elderly, lacks effective treatments. Many different types of vascular disease are included under the diagnosis of VCID, including large vessel disease with multiple strokes and small vessel disease with lacunar infarcts and white matter disease. Animal models have been developed to study the multiple forms of VCID. Because of its progressive course, small vessel disease (SVD) is thought to be the optimal form of VCID for treatment. One theory is that the pathophysiology involves hypoxic hypoperfusion resulting in injury to the white matter and neuronal death. Bilateral occlusion of the common carotid arteries (BCAO) in a normotensive rat, which reduces cerebral blood flow, induces hypoxia with white matter damage; this model has been used to test drugs to block the injury. Another model is the spontaneously hypertensive/stroke prone rat (SHR/SP). Hypertension leads to small vessel disease resulting in progressive damage to the white matter, cortex, and hippocampus. Bilateral carotid artery stenosis (BCAS) with coils or ameroid constrictors produces a slower development of changes than BCAO, avoiding the acute ischemia. A few studies have been done with the two-clip, two-vessel occlusion renal model for induction of hypertension. There are benefits and drawbacks to each of these models with the model selected depending on the type of vascular damage that is to be studied. This review describes the most commonly used models, and the drugs that have been used to reduce the damage. PMID:27498679

  4. How do bryophytes govern generative recruitment of vascular plants?

    PubMed

    Soudzilovskaia, Nadejda A; Graae, Bente J; Douma, Jacob C; Grau, Oriol; Milbau, Ann; Shevtsova, Anna; Wolters, Loes; Cornelissen, Johannes H C

    2011-06-01

    Interactions between vascular plants and bryophytes determine plant community composition in many ecosystems. Yet, little is known about the importance of interspecific differences between bryophytes with respect to their effects on vascular plants. We compared the extent to which species-specific bryophyte effects on vascular plant generative recruitment depend on the following underlying mechanisms: allelopathy, mechanical obstruction, soil moisture and temperature control. We sowed 10 vascular plant species into monospecific mats of six chemically and structurally diverse bryophytes, and examined 1-yr seedling recruitment. Allelopathic effects were also assessed in a laboratory phyto-assay. Although all bryophytes suppressed vascular plant regeneration, there were significant differences between the bryophyte species. The lack of interactions indicated the absence of species-specific adaptations of vascular plants for recruitment in bryophyte mats. Differences between bryophyte species were best explained by alterations in temperature regime under bryophyte mats, mostly by reduced temperature amplitudes during germination. The temperature regime under bryophyte mats was well predicted by species-specific bryophyte cushion thickness. The fitness of established seedlings was not affected by the presence of bryophytes. Our results suggest that climatically or anthropogenically driven changes in the species' composition of bryophyte communities have knock-on effects on vascular plant populations via generative reproduction.

  5. Activation of Nrf2 by dimethyl fumarate improves vascular calcification.

    PubMed

    Ha, Chae-Myeong; Park, Sungmi; Choi, Young-Keun; Jeong, Ji-Yun; Oh, Chang Joo; Bae, Kwi-Hyun; Lee, Sun Joo; Kim, Ji-Hyun; Park, Keun-Gyu; Jun, Do Youn; Lee, In-Kyu

    2014-10-01

    Dimethyl fumarate (DMF) has several pharmacological benefits including immunomodulation and prevention of fibrosis, which are dependent on the NF-E2-related factor 2 (Nrf2) antioxidant pathways. Therefore, we hypothesized that DMF could attenuate vascular calcification via Nrf2 activation. Vascular calcification induced by hyperphosphataemia was significantly inhibited by DMF in vascular smooth muscle cells (VSMCs) in a dose-dependent manner. DMF-mediated Nrf2 upregulation was accompanied by the reduced expressions of genes related with osteoblast-like phenotype based on promoter activity, mRNA and protein expression, and von Kossa staining. Likewise, Nrf2 overexpression significantly decreased the formation of calcium deposit similar to the level of osteogenic staining in VSMCs, and DMF with Nrf2 knockdown failed to attenuate hyperphosphatemia induced vascular calcification. Furthermore, DMF significantly attenuated the calcification of ex vivo ring culture from both rat common carotid artery and mouse thoracic aorta as well as in vivo mouse model of Vitamin D3-induced calcification consistent with the increased Nrf2 protein levels in early stage of calcification by DMF. In conclusion, our data support that DMF stimulates Nrf2 activity to attenuate hyperphosphatamia in vitro or Vitamin D3-induced in vivo vascular calcification, which would be a beneficial effect on vascular diseases induced by oxidative stress such as vascular calcification. PMID:25135648

  6. Vascular surgery: the European perspective.

    PubMed

    Harris, P

    1999-09-01

    Isaac Newton, among others, observed that 'we see so far because we are standing upon the shoulders of giants'. In vascular surgery most of the giants have been European, and this is a heritage which we as Europeans can take pride in and build upon if we chose to do so. As in other areas of life, commitment is essential in order to influence the future. For vascular surgeons in Europe this means active participation in the European scientific societies for vascular surgery and in the UEMS. The main value of the EBSQ.VASC assessments to date has been to expose the uneven standards of training in vascular surgery within the European Union. Only if action follows to address these inequalities will the tactics of the European Board of Vascular Surgery be vindicated.

  7. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  8. Vascular Dysfunction in Horses with Endocrinopathic Laminitis

    PubMed Central

    Morgan, Ruth A.; Keen, John A.; Walker, Brian R.; Hadoke, Patrick W. F.

    2016-01-01

    Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing’s disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing’s syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10−9–10-5M) and 5-hydroxytryptamine (5HT; 10−9–10-5M) and the vasodilator acetylcholine (10−9–10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof. PMID:27684374

  9. Neurite Mistargeting and Inverse Order of Intraretinal Vascular Plexus Formation Precede Subretinal Vascularization in Vldlr Mutant Mice

    PubMed Central

    Johnson, Verity; Xiang, Mengqing; Chen, Zhe; Junge, Harald J.

    2015-01-01

    In the retina blood vessels are required to support a high metabolic rate, however, uncontrolled vascular growth can lead to impaired vision and blindness. Subretinal vascularization (SRV), one type of pathological vessel growth, occurs in retinal angiomatous proliferation and proliferative macular telangiectasia. In these diseases SRV originates from blood vessels within the retina. We use mice with a targeted disruption in the Vldl-receptor (Vldlr) gene as a model to study SRV with retinal origin. We find that Vldlr mRNA is strongly expressed in the neuroretina, and we observe both vascular and neuronal phenotypes in Vldlr-/- mice. Unexpectedly, horizontal cell (HC) neurites are mistargeted prior to SRV in this model, and the majority of vascular lesions are associated with mistargeted neurites. In Foxn4-/- mice, which lack HCs and display reduced amacrine cell (AC) numbers, we find severe defects in intraretinal capillary development. However, SRV is not suppressed in Foxn4-/-;Vldlr-/- mice, which reveals that mistargeted HC neurites are not required for vascular lesion formation. In the absence of VLDLR, the intraretinal capillary plexuses form in an inverse order compared to normal development, and subsequent to this early defect, vascular proliferation is increased. We conclude that SRV in the Vldlr-/- model is associated with mistargeted neurites and that SRV is preceded by altered retinal vascular development. PMID:26177550

  10. Pressurized vascular systems for self-healing materials

    PubMed Central

    Hamilton, A. R.; Sottos, N. R.; White, S. R.

    2012-01-01

    An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen. PMID:21957119

  11. Vascular Inflammatory Cells in Hypertension

    PubMed Central

    Harrison, David G.; Marvar, Paul J.; Titze, Jens M.

    2012-01-01

    Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease. PMID:22586409

  12. In vivo quantitative evaluation of vascular parameters for angiogenesis based on sparse principal component analysis and aggregated boosted trees

    NASA Astrophysics Data System (ADS)

    Zhao, Fengjun; Liu, Junting; Qu, Xiaochao; Xu, Xianhui; Chen, Xueli; Yang, Xiang; Cao, Feng; Liang, Jimin; Tian, Jie

    2014-12-01

    To solve the multicollinearity issue and unequal contribution of vascular parameters for the quantification of angiogenesis, we developed a quantification evaluation method of vascular parameters for angiogenesis based on in vivo micro-CT imaging of hindlimb ischemic model mice. Taking vascular volume as the ground truth parameter, nine vascular parameters were first assembled into sparse principal components (PCs) to reduce the multicolinearity issue. Aggregated boosted trees (ABTs) were then employed to analyze the importance of vascular parameters for the quantification of angiogenesis via the loadings of sparse PCs. The results demonstrated that vascular volume was mainly characterized by vascular area, vascular junction, connectivity density, segment number and vascular length, which indicated they were the key vascular parameters for the quantification of angiogenesis. The proposed quantitative evaluation method was compared with both the ABTs directly using the nine vascular parameters and Pearson correlation, which were consistent. In contrast to the ABTs directly using the vascular parameters, the proposed method can select all the key vascular parameters simultaneously, because all the key vascular parameters were assembled into the sparse PCs with the highest relative importance.

  13. Lifestyle and metabolic approaches to maximizing erectile and vascular health.

    PubMed

    Meldrum, D R; Gambone, J C; Morris, M A; Esposito, K; Giugliano, D; Ignarro, L J

    2012-01-01

    Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient

  14. Vascular aspects of cognitive impairment and dementia.

    PubMed

    Wiesmann, Maximilian; Kiliaan, Amanda J; Claassen, Jurgen A H R

    2013-11-01

    Hypertension and stroke are highly prevalent risk factors for cognitive impairment and dementia. Alzheimer's disease (AD) and vascular dementia (VaD) are the most common forms of dementia, and both conditions are preceded by a stage of cognitive impairment. Stroke is a major risk factor for the development of vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose to AD. Hypertension is a major risk factor for stroke, thus linking hypertension to VCI and VaD, but hypertension is also an important risk factor for AD. Reducing these two major, but modifiable, risk factors-hypertension and stroke-could be a successful strategy for reducing the public health burden of cognitive impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) and the manipulation of factors involved in the renin-angiotensin system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to reduce the risk of developing hypertension and stroke, thereby reducing dementia risk. This paper will review the research conducted on the relationship between hypertension, stroke, and dementia and also on the impact of LC-n3-FA or antihypertensive treatments on risk factors for VCI, VaD, and AD. PMID:24022624

  15. Vascular aspects of cognitive impairment and dementia

    PubMed Central

    Wiesmann, Maximilian; Kiliaan, Amanda J; Claassen, Jurgen AHR

    2013-01-01

    Hypertension and stroke are highly prevalent risk factors for cognitive impairment and dementia. Alzheimer's disease (AD) and vascular dementia (VaD) are the most common forms of dementia, and both conditions are preceded by a stage of cognitive impairment. Stroke is a major risk factor for the development of vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose to AD. Hypertension is a major risk factor for stroke, thus linking hypertension to VCI and VaD, but hypertension is also an important risk factor for AD. Reducing these two major, but modifiable, risk factors—hypertension and stroke—could be a successful strategy for reducing the public health burden of cognitive impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) and the manipulation of factors involved in the renin–angiotensin system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to reduce the risk of developing hypertension and stroke, thereby reducing dementia risk. This paper will review the research conducted on the relationship between hypertension, stroke, and dementia and also on the impact of LC-n3-FA or antihypertensive treatments on risk factors for VCI, VaD, and AD. PMID:24022624

  16. Geriatric syndromes--vascular disorders?

    PubMed

    Strandberg, Timo E; Pitkälä, Kaisu H; Tilvis, Reijo S; O'Neill, Desmond; Erkinjuntti, Timo J

    2013-05-01

    The term geriatric syndrome is used to characterize multifactorial clinical conditions among older people which are not subsumed readily into disease entities, but which nevertheless predispose older people to disability and death. Commonly included are frailty, dementia, delirium, incontinence, falls, and dizziness. Geriatric syndromes are common among older people: in a recent survey, 50% of those aged more than 65 had one or more of these conditions. Better methods for prevention and treatment are needed, but current strategies have lacked a coherent conceptual and diagnostic framework. Prevention and interventions need to be targeted at earlier ages, with geriatrics expertise needed in the definition and operationalization of these complex entities. In this review we consolidate evidence that vascular disorders, including vascular ageing and vascular diseases, are key etiological factors of geriatric syndromes. Identifying this vascular dimension would offer opportunities for more efficient preventive strategies and mandates earlier intervention, especially for women, among whom vascular disease is often expressed more insidiously than among men. This would entail a sensitization of the health care system to the systematic detection of the syndromes, which are currently underdiagnosed. Further disentangling of the mechanisms of vascular ageing may offer therapies for vascular diseases and geriatric syndromes alike.

  17. Overgrowth syndromes with vascular anomalies.

    PubMed

    Blei, Francine

    2015-04-01

    Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. PMID:25937473

  18. [The future of vascular medicine].

    PubMed

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step.

  19. Vascular Injuries: Trends in Management

    PubMed Central

    Wani, Mohd Lateef; Ahangar, Ab Gani; Ganie, Farooq Ahmad; Wani, Shadab Nabi; Wani, Nasir-ud-din

    2012-01-01

    Abstract Vascular injury presents a great challenge to the emergency resident because these injuries require urgent intervention to prevent loss of life or limb. Sometimes serious vascular injury presents with only subtle or occult signs or symptoms. The patient may present weeks or months after initial injury with symptoms of vascular insufficiency, embolization, pseudoaneurysm, arteriovenous fistula etc. Although the majority of vascular injuries are caused by penetrating trauma from gunshot wounds, stabbing or blast injury, the possibility of vascular injury needs to be considered in patients presenting with displaced long bone fractures, crush injury, prolonged immobilization in a fixed position by tight casts or bandages and various invasive procedures. iatrogenic vascular injuries constitute about 10% of cases in most series; however the incidence is an increasing trend because more endovascular procedures such as angioplasty and cardiac catheterization are being performed routinely. Civilian trauma is more frequently seen in young males. However, it can occur at any age due to road accidents, firearms, bomb blasts and diagnostic procedures. Most of the time, civilian trauma causes less tissue damage. There is an epidemic of vascular injuries in Kashmir valley because of problems in law and order in the past two decades. This review deals with the topic in detail. PMID:24350103

  20. Overgrowth syndromes with vascular anomalies.

    PubMed

    Blei, Francine

    2015-04-01

    Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations.

  1. The Society for Vascular Surgery Vascular Quality Initiative.

    PubMed

    Cronenwett, Jack L; Kraiss, Larry W; Cambria, Richard P

    2012-05-01

    The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) is designed to improve the quality, safety, effectiveness, and cost of vascular health care. It uses the structure of a Patient Safety Organization to permit collection of patient-identified information but protect benchmarked comparisons from legal discovery. The SVS VQI is uniquely organized as a distributed network of regional quality groups to facilitate local translation of registry data into practice change while maintaining the power of a national registry. Detailed data specific to each commonly performed open and endovascular procedure are collected, both in-hospital and at ≥ 1 year of follow-up. Quality measures are reported to physicians and hospitals, which allow anonymous risk-adjusted benchmarking within regions or nationally. All specialties that perform vascular procedures are included, and international participation is encouraged. This review describes the current status of the SVS VQI.

  2. Defining excellence in vascular neurosurgery.

    PubMed

    Sanai, Nader; Spetzler, Robert F

    2010-01-01

    Success as a vascular neurosurgeon almost always begins with passion, an inherent love for the work that drives an insatiable desire for personal improvement. A personal definition of excellence in vascular neurosurgery includes several fundamental qualities: mastery of the basics, refinement of technique, advancement of technology, investigative study, advanced decision making, microsurgical innovation, a well-rounded surgical armamentarium, and a lifelong commitment to teaching. Ultimately, the reward for these efforts is the ability to influence generations to come, particularly as one follows the rising careers of former trainees, each redefining the term "excellence" in vascular neurosurgery.

  3. Gasotransmitters in Vascular Complications of Diabetes.

    PubMed

    van den Born, Joost C; Hammes, Hans-Peter; Greffrath, Wolfgang; van Goor, Harry; Hillebrands, Jan-Luuk

    2016-02-01

    In the past decades three gaseous signaling molecules-so-called gasotransmitters-have been identified: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These gasotransmitters are endogenously produced by different enzymes in various cell types and play an important role in physiology and disease. Despite their specific functions, all gasotransmitters share the capacity to reduce oxidative stress, induce angiogenesis, and promote vasorelaxation. In patients with diabetes, a lower bioavailability of the different gasotransmitters is observed when compared with healthy individuals. As yet, it is unknown whether this reduction precedes or results from diabetes. The increased risk for vascular disease in patients with diabetes, in combination with the extensive clinical, financial, and societal burden, calls for action to either prevent or improve the treatment of vascular complications. In this Perspective, we present a concise overview of the current data on the bioavailability of gasotransmitters in diabetes and their potential role in the development and progression of diabetes-associated microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (cerebrovascular, coronary artery, and peripheral arterial diseases) complications. Gasotransmitters appear to have both inhibitory and stimulatory effects in the course of vascular disease development. This Perspective concludes with a discussion on gasotransmitter-based interventions as a therapeutic option.

  4. Neuroprotective effects of tetrandrine against vascular dementia

    PubMed Central

    Lv, Yan-ling; Wu, Ze-zhi; Chen, Li-xue; Wu, Bai-xue; Chen, Lian-lian; Qin, Guang-cheng; Gui, Bei; Zhou, Ji-ying

    2016-01-01

    Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S. Moore, and has specific therapeutic effects in ischemic cerebrovascular disease. Its use in vascular dementia has not been studied fully. Here, we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia. Eight weeks after model establishment, rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks. Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials, and spent less time swimming in the target quadrant in probe trials, than sham-operated rats. However, rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats. Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage, and more living cells, in the hippocampus of rats treated with tetrandrine than in untreated model rats. Western blot assay showed that interleukin-1β expression, and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472, were lower in model rats that received tetrandrine than in those that did not. The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression, N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472, and neuronal necrosis. PMID:27127485

  5. Neuroprotective effects of tetrandrine against vascular dementia.

    PubMed

    Lv, Yan-Ling; Wu, Ze-Zhi; Chen, Li-Xue; Wu, Bai-Xue; Chen, Lian-Lian; Qin, Guang-Cheng; Gui, Bei; Zhou, Ji-Ying

    2016-03-01

    Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S. Moore, and has specific therapeutic effects in ischemic cerebrovascular disease. Its use in vascular dementia has not been studied fully. Here, we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia. Eight weeks after model establishment, rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks. Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials, and spent less time swimming in the target quadrant in probe trials, than sham-operated rats. However, rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats. Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage, and more living cells, in the hippocampus of rats treated with tetrandrine than in untreated model rats. Western blot assay showed that interleukin-1β expression, and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472, were lower in model rats that received tetrandrine than in those that did not. The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression, N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472, and neuronal necrosis. PMID:27127485

  6. Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

    PubMed Central

    Su, Jie; Xu, Han-Ting; Yu, Jing-Jing; Gao, Jian-Li; Lei, Jing; Yin, Qiao-Shan; Li, Bo; Pang, Min-Xia; Su, Min-Xia; Mi, Wen-Jia; Chen, Su-Hong; Lv, Gui-Yuan

    2015-01-01

    Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS. PMID:26495010

  7. Retina vascular network recognition

    NASA Astrophysics Data System (ADS)

    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.

  8. Constructal vascularized structures

    NASA Astrophysics Data System (ADS)

    Cetkin, Erdal

    2015-06-01

    Smart features such as self-healing and selfcooling require bathing the entire volume with a coolant or/and healing agent. Bathing the entire volume is an example of point to area (or volume) flows. Point to area flows cover all the distributing and collecting kinds of flows, i.e. inhaling and exhaling, mining, river deltas, energy distribution, distribution of products on the landscape and so on. The flow resistances of a point to area flow can be decreased by changing the design with the guidance of the constructal law, which is the law of the design evolution in time. In this paper, how the flow resistances (heat, fluid and stress) can be decreased by using the constructal law is shown with examples. First, the validity of two assumptions is surveyed: using temperature independent Hess-Murray rule and using constant diameter ducts where the duct discharges fluid along its edge. Then, point to area types of flows are explained by illustrating the results of two examples: fluid networks and heating an area. Last, how the structures should be vascularized for cooling and mechanical strength is documented. This paper shows that flow resistances can be decreased by morphing the shape freely without any restrictions or generic algorithms.

  9. Vascular Effects of Dietary Advanced Glycation End Products

    PubMed Central

    Stirban, Alin; Tschöpe, Diethelm

    2015-01-01

    Evidence has accumulated lately demonstrating that advanced glycation end products (AGEs) play an important role in the development of diabetic and cardiovascular complications as well as the development of other chronic diseases. AGEs originating from diet have a significant contribution to the AGEs body pool and therefore dietary interventions aiming at reducing AGEs load are believed to exert health promoting effects. This review summarizes the evidence from clinical studies regarding effects of dietary AGEs on the vascular system, highlighting also the different aspects of vascular tests. It also advocates an extension of dietary recommendations towards the promotion of cooking methods that reduce dietary AGEs in consumed foods. PMID:26089897

  10. Regional intensity of vascular care and lower extremity amputation rates

    PubMed Central

    Goodney, Philip P.; Holman, Kerianne; Henke, Peter K.; Travis, Lori L.; Dimick, Justin B.; Stukel, Therese A.; Fisher, Elliott. S.; Birkmeyer, John D.

    2013-01-01

    , although the observational nature of associations do not impart causality. High-risk patients, especially African-American diabetic patients residing in low-intensity vascular care regions, represent an important target for systematic efforts to reduce amputation risk. PMID:23375611

  11. A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury

    PubMed Central

    Ho, Yen-Chun; Wu, Meng-Ling; Su, Chen-Hsuan; Chen, Chung-Huang; Ho, Hua-Hui; Lee, Guan-Lin; Lin, Wei-Shiang; Lin, Wen-Yu; Hsu, Yu-Juei; Kuo, Cheng-Chin; Wu, Kenneth K.; Yet, Shaw-Fang

    2016-01-01

    5-Methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, was recently shown to suppress inflammatory mediator-induced cancer cell proliferation and migration. However, the role of 5-MTP in vascular disease is unknown. In this study, we investigated whether 5-MTP protects against vascular remodeling following arterial injury. Measurements of serum 5-MTP levels in healthy subjects and patients with coronary artery disease (CAD) showed that serum 5-MTP concentrations were inversely correlated with CAD. To test the role of 5-MTP in occlusive vascular disease, we subjected mice to a carotid artery ligation model of neointima formation and treated mice with vehicle or 5-MTP. Compared with vehicle-treated mice, 5-MTP significantly reduced intimal thickening by 40% 4 weeks after ligation. BrdU incorporation assays revealed that 5-MTP significantly reduced VSMC proliferation both in vivo and in vitro. Furthermore, 5-MTP reduced endothelial loss and detachment, ICAM-1 and VCAM-1 expressions, and inflammatory cell infiltration in the ligated arterial wall, suggesting attenuation of endothelial dysfunction. Signaling pathway analysis indicated that 5-MTP mediated its effects predominantly via suppressing p38 MAPK signaling in endothelial and VSMCs. Our data demonstrate a novel vascular protective function of 5-MTP against arterial injury-induced intimal hyperplasia. 5-MTP might be a therapeutic target for preventing and/or treating vascular remodeling. PMID:27146795

  12. BMP signaling in vascular diseases.

    PubMed

    Cai, Jie; Pardali, Evangelia; Sánchez-Duffhues, Gonzalo; ten Dijke, Peter

    2012-07-01

    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) family that signal via type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. BMPs are multifunctional regulators of development and tissue homeostasis and they were initially characterized as inducers of bone regeneration. Genetic studies in humans and mice showed that perturbations in BMP signaling lead to various diseases, such as skeletal diseases, vascular diseases and cancer. Mutations in BMP type II receptor and BMP type I receptor/activin receptor-like kinase 1 have been linked to pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia, respectively. BMPs have also been implicated in promoting vascular calcification and tumor angiogenesis. In this review we discuss the role of BMP signaling in vascular diseases and the value of BMP signaling as a vascular disease marker or a therapeutic target. PMID:22710160

  13. Biomaterials for vascular tissue engineering

    PubMed Central

    Ravi, Swathi; Chaikof, Elliot L

    2010-01-01

    Cardiovascular disease is the leading cause of mortality in the USA. The limited availability of healthy autologous vessels for bypass grafting procedures has led to the fabrication of prosthetic vascular conduits. While synthetic polymers have been extensively studied as substitutes in vascular engineering, they fall short of meeting the biological challenges at the blood–material interface. Various tissue engineering strategies have emerged to address these flaws and increase long-term patency of vascular grafts. Vascular cell seeding of scaffolds and the design of bioactive polymers for in situ arterial regeneration have yielded promising results. This article describes the advances made in biomaterials design to generate suitable materials that not only match the mechanical properties of native vasculature, but also promote cell growth, facilitate extracellular matrix production and inhibit thrombogenicity. PMID:20017698

  14. Tissue engineering: Perfusable vascular networks

    NASA Astrophysics Data System (ADS)

    Forgacs, Gabor

    2012-09-01

    A rapid vascular casting approach that uses carbohydrate glass as a sacrificial template allows tissues to be built that can be kept alive for longer in the laboratory until needed for transplantation.

  15. Measuring Vascular Permeability In Vivo.

    PubMed

    Meijer, Eelco F J; Baish, James W; Padera, Timothy P; Fukumura, Dai

    2016-01-01

    Over the past decades, in vivo vascular permeability measurements have provided significant insight into vascular functions in physiological and pathophysiological conditions such as the response to pro- and anti-angiogenic signaling, abnormality of tumor vasculature and its normalization, and delivery and efficacy of therapeutic agents. Different approaches for vascular permeability measurements have been established. Here, we describe and discuss a conventional 2D imaging method to measure vascular permeability, which was originally documented by Gerlowski and Jain in 1986 (Microvasc Res 31:288-305, 1986) and further developed by Yuan et al. in the early 1990s (Microvasc Res 45:269-289, 1993; Cancer Res 54:352-3356, 1994), and our recently developed 3D imaging method, which advances the approach originally described by Brown et al. in 2001 (Nat Med 7:864-868, 2001). PMID:27581015

  16. How to Prevent Vascular Disease

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  17. Social media in vascular surgery.

    PubMed

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

    2013-04-01

    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. PMID:23321344

  18. Vascular heterogeneity in the kidney.

    PubMed

    Molema, Grietje; Aird, William C

    2012-03-01

    Blood vessels and their endothelial lining are uniquely adapted to the needs of the underlying tissue. The structure and function of the vasculature varies both between and within different organs. In the kidney, the vascular architecture is designed to function both in oxygen/nutrient delivery and filtration of blood according to the homeostatic needs of the body. Here, we review spatial and temporal differences in renal vascular phenotypes in both health and disease.

  19. Regulated Hyaluronan Synthesis by Vascular Cells

    PubMed Central

    Viola, Manuela; Karousou, Evgenia; D'Angelo, Maria Luisa; Caon, Ilaria; De Luca, Giancarlo; Passi, Alberto; Vigetti, Davide

    2015-01-01

    Cellular microenvironment plays a critical role in several pathologies including atherosclerosis. Hyaluronan (HA) content often reflects the progression of this disease in promoting vessel thickening and cell migration. HA synthesis is regulated by several factors, including the phosphorylation of HA synthase 2 (HAS2) and other covalent modifications including ubiquitination and O-GlcNAcylation. Substrate availability is important in HA synthesis control. Specific drugs reducing the UDP precursors are able to reduce HA synthesis whereas the hexosamine biosynthetic pathway (HBP) increases the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc) leading to an increase of HA synthesis. The flux through the HBP in the regulation of HA biosynthesis in human aortic vascular smooth muscle cells (VSMCs) was reported as a critical aspect. In fact, inhibiting O-GlcNAcylation reduced HA production whereas increased O-GlcNAcylation augmented HA secretion. Additionally, O-GlcNAcylation regulates HAS2 gene expression resulting in accumulation of its mRNA after induction of O-GlcNAcylation with glucosamine treatments. The oxidized LDLs, the most common molecules related to atherosclerosis outcome and progression, are also able to induce a strong HA synthesis when they are in contact with vascular cells. In this review, we present recent described mechanisms involved in HA synthesis regulation and their role in atherosclerosis outcome and development. PMID:26448750

  20. Multimodality imaging of vascular anomalies.

    PubMed

    Restrepo, Ricardo

    2013-03-01

    Vascular malformations and hemangiomas are common in children but remain a source of confusion during diagnosis, in part because of the lack of a uniform terminology. With the existing treatments for hemangiomas and vascular malformations, it is important to make the correct diagnosis initially to prevent adverse physical and emotional sequelae in not only the child but also the family. The diagnosis of vascular malformations is made primarily by the clinician and based on the physical exam. Imaging is carried out using predominantly ultrasound (US) and magnetic resonance imaging (MRI), which are complementary modalities. In most cases of vascular anomalies, US is the first line of imaging as it is readily available, less expensive, lacks ionizing radiation and does not require sedation. MRI is also of great help for further characterizing the lesions. Conventional arteriography is reserved for cases that require therapeutic intervention, more commonly for arteriovenous malformations. Radiographs usually play no role in diagnosing vascular anomalies in children. In this article, the author describes the terminology and types of hemangiomas and vascular malformations and their clinical, histological features, as well as the imaging approach and appearance.

  1. Contractile properties of isolated vascular smooth muscle after photoradiation

    SciTech Connect

    Freas, W.; Hart, J.L.; Golightly, D.; McClure, H.; Muldoon, S.M.

    1989-03-01

    The purpose of this study was to characterize the responses of various types of vascular smooth muscle to conditions that would be encountered during photodynamic therapy, namely laser illumination of photosensitizer-pretreated tissue. Vascular smooth muscle obtained from representative canine, rodent, and rabbit vascular beds was cut into rings and placed in organ baths (37 degrees C, aerated with 95% O2-5% CO2). These vessels were pretreated for 30 min with the photosensitizer hematoporphyrin derivative (HpD, 3-30 micrograms/ml) washed, and then exposed to red laser light (633 nm, 1-3.5 mW) for up to 20 min. Under basal tension conditions laser illumination of HpD-pretreated vessels resulted in an increase in tension, whereas laser illumination of vessels not exposed to HpD did not contract. This sustained contraction was not reversed by washing the tissue with fresh Krebs-Ringer solution. Responses to norepinephrine, transmural electrical stimulation, and elevated concentrations of KCl were reduced in blood vessels tested after HpD laser illumination. Laser-induced contractions of canine carotid arteries did not require the presence of an intact vascular endothelium. Vascular effect of these photosensitizers appears to involve the formation of oxygen-derived radicals. This preparation could provide a good model for examining the effects of free radicals on vascular physiology.

  2. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    PubMed Central

    Nicolosi, Pier Andrea; Tombetti, Enrico; Maugeri, Norma; Rovere-Querini, Patrizia; Brunelli, Silvia; Manfredi, Angelo A.

    2016-01-01

    Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment. PMID:27069480

  3. Angiopoietin-2 is critical for cytokine-induced vascular leakage.

    PubMed

    Benest, Andrew V; Kruse, Karoline; Savant, Soniya; Thomas, Markus; Laib, Anna M; Loos, Elias K; Fiedler, Ulrike; Augustin, Hellmut G

    2013-01-01

    Genetic experiments (loss-of-function and gain-of-function) have established the role of Angiopoietin/Tie ligand/receptor tyrosine kinase system as a regulator of vessel maturation and quiescence. Angiopoietin-2 (Ang-2) acts on Tie2-expressing resting endothelial cells as an antagonistic ligand to negatively interfere with the vessel stabilizing effects of constitutive Ang-1/Tie-2 signaling. Ang-2 thereby controls the vascular response to inflammation-inducing as well as angiogenesis-inducing cytokines. This study was aimed at assessing the role of Ang-2 as an autocrine (i.e. endothelial-derived) regulator of rapid vascular responses (within minutes) caused by permeability-inducing agents. Employing two independent in vivo assays to quantitatively assess vascular leakage (tracheal microsphere assay, 1-5 min and Miles assay, 20 min), the immediate vascular response to histamine, bradykinin and VEGF was analyzed in Ang-2-deficient (Ang-2(-/-)) mice. In comparison to the wild type control mice, the Ang2(-/-) mice demonstrated a significantly attenuated response. The Ang-2(-/-) phenotype was rescued by systemic administration (paracrine) of an adenovirus encoding Ang-2. Furthermore, cytokine-induced intracellular calcium influx was impaired in Ang-2(-/-) endothelioma cells, consistent with reduced phospholipase activation in vivo. Additionally, recombinant human Ang-2 (rhAng-2) alone was unable to induce vascular leakage. In summary, we report here in a definite genetic setting that Ang-2 is critical for multiple vascular permeability-inducing cytokines. PMID:23940579

  4. Aerobic exercise and other healthy lifestyle factors that influence vascular aging.

    PubMed

    Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R

    2014-12-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. PMID:25434012

  5. CD8 T Cell-Initiated Vascular Endothelial Growth Factor Expression Promotes Central Nervous System Vascular Permeability under Neuroinflammatory Conditions

    PubMed Central

    Suidan, Georgette L.; Dickerson, Jonathan W.; Chen, Yi; McDole, Jeremiah R.; Tripathi, Pulak; Pirko, Istvan; Seroogy, Kim B.; Johnson, Aaron J.

    2010-01-01

    Dysregulation of the blood-brain barrier (BBB) is a hallmark feature of numerous neurologic disorders as diverse as multiple sclerosis, stroke, epilepsy, viral hemorrhagic fevers, cerebral malaria, and acute hemorrhagic leukoencephalitis. CD8 T cells are one immune cell type that have been implicated in promoting vascular permeability in these conditions. Our laboratory has created a murine model of CD8 T cell-mediated CNS vascular permeability using a variation of the Theiler’s murine encephalomyelitis virus system traditionally used to study multiple sclerosis. Previously, we demonstrated that CD8 T cells have the capacity to initiate astrocyte activation, cerebral endothelial cell tight junction protein alterations and CNS vascular permeability through a perforin-dependent process. To address the downstream mechanism by which CD8 T cells promote BBB dysregulation, in this study, we assess the role of vascular endothelial growth factor (VEGF) expression in this model. We demonstrate that neuronal expression of VEGF is significantly upregulated prior to, and coinciding with, CNS vascular permeability. Phosphorylation of fetal liver kinase-1 is significantly increased early in this process indicating activation of this receptor. Specific inhibition of neuropilin-1 significantly reduced CNS vascular permeability and fetal liver kinase-1 activation, and preserved levels of the cerebral endothelial cell tight junction protein occludin. Our data demonstrate that CD8 T cells initiate neuronal expression of VEGF in the CNS under neuroinflammatory conditions, and that VEGF may be a viable therapeutic target in neurologic disease characterized by inflammation-induced BBB disruption. PMID:20008293

  6. Laser-assisted vascular anastomosis

    NASA Astrophysics Data System (ADS)

    Kao, Race L.; Tsao-Wu, George; Magovern, George J.

    1990-06-01

    The milliwatt CO2 laser and a thermal activated binding compound (20% serum albumin) were used for microvascular anastomoses. Under general anesthesia, the femoral arteries (0.7 to 1.0 mm diameter) of 6 rats were isolated. After the left femoral artery in each rat was clamped and transected, the vessel was held together with 3 equidistant 10-0 Xomed sutures. The cut edges were coated 3 to 4 times with the albumin solution and sealed with the CO2 laser (power density = 120 W/cm2). The binding compound solidified to a translucent tensile substance which supported the anastomosis until self healing and repair were achieved. The right femoral artery was used as sham operated control. Complete hemostasis and patency were observed in every case immediately and at 1, 3, and 6 months following surgery. The binding compound absorbed most of the laser energy thus minimizing thermal injury to the underlying tissue. Mongrel dogs weighing 28 to 33 kg were anesthetized and prepared for sterile surgical procedures. In 5 dogs, the femoral and jugular veins were exposed, transected, and anastomosed using a CO2 laser (Sharplan 1040) with the binding compound. In another 12 dogs, cephalic veins were isolated and used for aortocoronary artery bypass procedures. The Sharplan 1040 CO2 laser and 20% albumin solution were utilized to complete the coronary anastomoses in 6 dogs, and 6 dogs were used as controls by suturing the vessels. Again, hemostasis, patency, and minimal tissue damage were observed immediately and 6 weeks after the procedures. Improved surgical results, reduced operating time, minimized tissue damage, and enhanced anastomotic integrity are the advantages of laser assisted vascular anastomosis with a thermal activated binding compound.

  7. Differentiation of Multipotent Vascular Stem Cells Contributes to Vascular Diseases

    PubMed Central

    Tang, Zhenyu; Wang, Aijun; Yuan, Falei; Yan, Zhiqiang; Liu, Bo; Chu, Julia S.; Helms, Jill A.

    2012-01-01

    It is generally accepted that the de-differentiation of smooth muscle cells (SMCs) from contractile to proliferative/synthetic phenotype has an important role during vascular remodeling and diseases. Here we provide evidence that challenges this theory. We identify a new type of multipotent vascular stem cell (MVSC) in blood vessel wall. MVSCs express markers including Sox17, Sox10 and S100β, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell (MSC)-like cells that subsequently differentiate into SMCs. On the other hand, we use lineage tracing with smooth muscle myosin heavy chain as a marker to show that MVSCs and proliferative or synthetic SMCs do not arise from the de-differentiation of mature SMCs. Upon vascular injuries, MVSCs, instead of SMCs, become proliferative, and MVSCs can differentiate into SMCs and chondrogenic cells, thus contributing to vascular remodeling and neointimal hyperplasia. These findings support a new hypothesis that the differentiation of MVSCs, rather than the de-differentiation of SMCs, contributes to vascular remodeling and diseases. PMID:22673902

  8. Early experience on peripheral vascular application of the vascular plugs

    PubMed Central

    Rohit, Manoj Kumar; Sinha, Alok Kumar; Kamana, Naveen Krishna

    2013-01-01

    Background Transcatheter closure of various congenital and acquired vascular malformations with Amplatzer Vascular plugs I and II has been established. Here we present our experience with device closure. Materials and methods Between October 2006 and August 2012, nine (three males and six females) patients aged between 11 months and 62 years (mean age 19 years) underwent percutaneous device closure with AVP I and II vascular plugs for congenital and acquired arteriovenous malformation and cardiac diverticulum are presented here. Results One case of coronary cameral fistula, four cases of pulmonary arteriovenous fistula, one case of large major aortopulmonary collaterals (in tetralogy of Fallot closed before intracardiac repair), one case of congenital cardiac diverticulum, one case of fistula between external carotid artery and internal jugular vein and one case of iatrogenic carotid jugular fistula were successfully closed with AVP I and II plugs. Overall in nine cases, 16 AVP I and II plugs were deployed to occlude feeding vessels and one cardiac diverticulum. The technical success rate was 100%. No major complications were observed. Conclusion Amplatzer vascular plugs can be used successfully for closure of various congenital and acquired vascular malformations with good result. PMID:24206877

  9. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

    PubMed Central

    Reinert, Rachel B.; Cai, Qing; Hong, Ji-Young; Plank, Jennifer L.; Aamodt, Kristie; Prasad, Nripesh; Aramandla, Radhika; Dai, Chunhua; Levy, Shawn E.; Pozzi, Ambra; Labosky, Patricia A.; Wright, Christopher V. E.; Brissova, Marcela; Powers, Alvin C.

    2014-01-01

    Neurovascular alignment is a common anatomical feature of organs, but the mechanisms leading to this arrangement are incompletely understood. Here, we show that vascular endothelial growth factor (VEGF) signaling profoundly affects both vascularization and innervation of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGF-induced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers. PMID:24574008

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

    PubMed Central

    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

  11. Protective role of sulphoraphane against vascular complications in diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Matsui, Takanori

    2016-10-01

    Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects. Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications. Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles. Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans. Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes. PMID:26841240

  12. Vascular tissue engineering: towards the next generation vascular grafts.

    PubMed

    Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

    2011-04-30

    The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. PMID:21421015

  13. Vascular changes in hard palate sialolipoma: Sialoangiolipoma or vascular malformation?

    PubMed Central

    Handra-Luca, Adriana

    2015-01-01

    Palate sialolipomas are rare. Less than 10 cases located in the hard palate are reported to our knowledge. We report a case of hard palate sialolipoma, peculiar by the intratumor vascular patterns. A 67-year-old man presented with a 1.5 cm lesion of the oral hard palate. The lesion was surgically resected. On microscopy, the lesion, partly encapsulated, consisted of a proliferation of mature adipocytes containing normal minor salivary gland tissue and branching intratumoral vessels of varied size with irregularly thickened wall and papillary projections or tufts. The microscopic features of the tumor we report suggest that vascular malformation-like patterns may occur in sialolipomas of the hard palate. This morphological vascular peculiarity should be acknowledged since it may represent source of hemorrhage. PMID:26604516

  14. The role of cellular senescence during vascular calcification: a key paradigm in aging research.

    PubMed

    Mackenzie, N C W; MacRae, V E

    2011-07-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events. Vascular calcification refers to the deposition of calcium phosphate mineral, most often hydroxyapatite, in arteries. Extensive calcification of the vascular system is a key characteristic of aging. In this article, we outline the mechanisms governing vascular calcification and highlight its association with cellular senescence. This review discusses the molecular mechanisms of cellular senescence and its affect on calcification of vascular cells, the relevance of phosphate regulation and the function of FGF23 and Klotho proteins. The association of vascular calcification and cellular senescence with the rare human aging disorder Hutchison-Gilford Progeria Syndrome (HGPS) is highlighted and the mouse models used to try to determine the underlying pathways are discussed. By understanding the pathways involved in these processes novel drug targets may be elucidated in an effort to reduce the effects of cellular aging as a risk factor in cardiovascular disease.

  15. Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex

    PubMed Central

    Lacoste, Baptiste; Comin, Cesar H.; Ben-Zvi, Ayal; Kaeser, Pascal S.; Xu, Xiaoyin; Costa, Luciano da F.; Gu, Chenghua

    2014-01-01

    SUMMARY Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations of vascular networks reveals a novel feature of neurovascular interactions. PMID:25155955

  16. Vascular effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fyodorov, Svyatoslav N.; Kopayeva, V. G.; Andreev, J. B.; Ponomarev, Gelii V.; Stranadko, Eugeny P.; Suchin, H. M.

    1996-01-01

    Vascular effect of PDT has been studied in patients with corneal vascularized leucomas (10 patients) and in patients with corneal neovascularized transplant (3 patients). For vascularized leucomas the method of photodynamic therapy consisted of the local injection of dimegin (deiteroporphyrin derivative) into the space of the newly-formed vessels under operating microscope (opton) with the microneedle (diameter 200 microns) and corneal irradiation by the operating microscope light. For corneal neovascularized transplant the injection of photogem (hematoporphyrin derivative) intravenously were made with subsequent irradiation by light of dye laser (5 hours after the injection) with light density of 150 mW/cm2 for 15 minutes. In all the cases at the time of irradiation the aggregated blood flow was appeared, followed by blood flow stasis. In postoperative period the vessels disintegrated into separate fragments which disappeared completely after 10 - 15 days. Taking into account the data of light microscopy, the disappearance of the vessels took place as a result of the vascular endothelium lisis along the vascular walls. Neovascularized cornea and newly-formed vessels in tumor stroms have much in common. The vessel alterations study presented in this paper, may serve to specify the mechanism of photodynamic destruction of neovascularized stroma of tumor.

  17. Vascular potassium channels in NVC.

    PubMed

    Yamada, K

    2016-01-01

    It has long been proposed that the external potassium ion ([K(+)]0) works as a potent vasodilator in the dynamic regulation of local cerebral blood flow. Astrocytes may play a central role for producing K(+) outflow possibly through calcium-activated potassium channels on the end feet, responding to a rise in the intracellular Ca(2+) concentration, which might well reflect local neuronal activity. A mild elevation of [K(+)]0 in the end feet/vascular smooth muscle space could activate Na(+)/K(+)-ATPase concomitant with inwardly rectifying potassium (Kir) channels in vascular smooth muscle cells, leading to a hyperpolarization of vascular smooth muscle and relaxation of smooth muscle actin-positive vessels. Also proposed notion is endothelial calcium-activated potassium channels and/or inwardly rectifying potassium channel-mediated hyperpolarization of vascular smooth muscle. A larger elevation of [K(+)]0, which may occur pathophysiologically in such as spreading depression or stroke, can trigger a depolarization of vascular smooth muscle cells and vasoconstriction instead. PMID:27130411

  18. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  19. Vascular gene expression: a hypothesis

    PubMed Central

    Martínez-Navarro, Angélica C.; Galván-Gordillo, Santiago V.; Xoconostle-Cázares, Beatriz; Ruiz-Medrano, Roberto

    2013-01-01

    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. PMID:23882276

  20. Vascular ultrasound for atherosclerosis imaging

    PubMed Central

    de Korte, Chris L.; Hansen, Hendrik H. G.; van der Steen, Anton F. W.

    2011-01-01

    Cardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the geometry of vessel walls and plaques. The high temporal as well as spatial resolution allows quantification of luminal area and plaque size and volume. While carotid arteries can be imaged non-invasively, scanning of coronary arteries requires invasive intravascular catheters. Both techniques have already demonstrated their clinical applicability. Using linear array technology, detection of disease as well as monitoring of pharmaceutical treatment in carotid arteries are feasible. Data acquired with intravascular ultrasound catheters have proved to be especially beneficial in understanding the development of atherosclerotic disease in coronary arteries. With the introduction of vascular elastography not only the geometry of plaques but also the risk for rupture of plaques might be identified. These so-called vulnerable plaques are frequently not flow-limiting and rupture of these plaques is responsible for the majority of cerebral and cardiac ischaemic events. Intravascular ultrasound elastography studies have demonstrated a high correlation between high strain and vulnerable plaque features, both ex vivo and in vivo. Additionally, pharmaceutical intervention could be monitored using this technique. Non-invasive vascular elastography has recently been developed for carotid applications by using compound scanning. Validation and initial clinical evaluation is currently being performed. Since abundance of vasa vasorum (VV) is correlated with vulnerable plaque development, quantification of VV might be a unique tool to even prevent this from happening. Using ultrasound contrast agents, it has been demonstrated that VV can be identified and quantified. Although far from routine

  1. The utility of digital subtraction arteriography in peripheral vascular disease.

    PubMed

    Kubal, W S; Crummy, A B; Turnipseed, W D

    1983-01-01

    Digital subtraction angiography (DSA), whether used in conjunction with intravenous or intraarterial injection techniques, has an established role in evaluation of peripheral vascular disease. Use of DSA can reduce the time, cost, and patient discomfort of the standard arteriographic study. While it is limited by field size and patient cooperation in some instances, the utility of noninvasive imaging using intravenous DSA and the added anatomic detail of intraarterial DSA for roadmapping and delineation of small distal vessels provide the basis for future integration of standard arteriographic and DSA methods in assessment of peripheral vascular disease. PMID:6228296

  2. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area. PMID:25926569

  3. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  4. Vascular contributions to cognitive impairment

    PubMed Central

    Flores, Alan

    2015-01-01

    Summary Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible VCI, summarize current treatment and prevention guidelines, and provide an overview with case examples. PMID:26124978

  5. Genetic basis for vascular anomalies.

    PubMed

    Kirkorian, A Yasmine; Grossberg, Anna L; Püttgen, Katherine B

    2016-03-01

    The fundamental genetics of many isolated vascular anomalies and syndromes associated with vascular anomalies have been elucidated. The rate of discovery continues to increase, expanding our understanding of the underlying interconnected molecular pathways. This review summarizes genetic and clinical information on the following diagnoses: capillary malformation, venous malformation, lymphatic malformation, arteriovenous malformation, PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, SOLAMEN syndrome, Sturge-Weber syndrome, phakomatosis pigmentovascularis, congenital hemangioma, verrucous venous malformation, cutaneomucosal venous malformation, blue rubber bleb nevus syndrome, capillary malformation-arteriovenous malformation syndrome, Parkes-Weber syndrome, and Maffucci syndrome. PMID:27607321

  6. Vascular Complications of Diabetes.

    PubMed

    Beckman, Joshua A; Creager, Mark A

    2016-05-27

    Over the last several decades, the global incidence and prevalence of diabetes mellitus has increased significantly. The raised incidence rate is projected to continue as greater numbers of persons adopt a Western lifestyle and diet. Patients with diabetes mellitus are at heightened risk of both adverse microvascular and cardiovascular events. Moreover, once cardiovascular disease develops, diabetes mellitus exacerbates progression and worsens outcomes. The medical management of patients with diabetes mellitus mandates comprehensive risk factor modification and antiplatelet therapy. Recent clinical trials of new medical therapies continue to inform the care of patients with diabetes mellitus to reduce both cardiovascular morbidity and mortality. PMID:27230641

  7. Impaired sympathetic vascular regulation in humans after acute dynamic exercise.

    PubMed Central

    Halliwill, J R; Taylor, J A; Eckberg, D L

    1996-01-01

    1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena. Images Figure 7 PMID:8866370

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

    PubMed Central

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

    2016-01-01

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

  9. [Mechanism of losartan suppressing vascular calcification in rat aortic artery].

    PubMed

    Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

    2016-08-01

    Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process. PMID:27412937

  10. Impaired sympathetic vascular regulation in humans after acute dynamic exercise

    NASA Technical Reports Server (NTRS)

    Halliwill, J. R.; Taylor, J. A.; Eckberg, D. L.

    1996-01-01

    1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena.

  11. Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

    PubMed

    Li, Peng; Yin, Ya-Ling; Zhu, Mo-Li; Pan, Guo-Pin; Zhao, Fan-Rong; Lu, Jun-Xiu; Liu, Zhan; Wang, Shuang-Xi; Hu, Chang-Ping

    2016-04-01

    Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. PMID:26818681

  12. Overgrowth syndromes with vascular malformations.

    PubMed

    Hagen, Solveig L; Hook, Kristen P

    2016-03-01

    This review provides a clinically-oriented summary of the most commonly encountered overgrowth syndromes associated with vascular malformations. This manuscript will outline morphologic features, clinical evaluation and management of this complex group of patients. Recent genetic advances have aided in classification and help to explain overlapping clinical features in many cases. PMID:27607325

  13. The relationships of vascular plants.

    PubMed Central

    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). The implications of recent phylogenetic work are discussed with reference to life cycle evolution and the interpretation of stratigraphic inconsistencies in the early fossil record of land plants. Life cycles are shown to have passed through an isomorphic phase in the early stages of vascular plant evolution. Thus, the gametophyte generation of all living vascular plants is the product of massive morphological reduction. Phylogenetic research corroborates earlier suggestions of a major representational bias in the early fossil record. Mega-fossils document a sequence of appearance of groups that is at odds with that predicted by cladogram topology. It is argued here that the pattern of appearance and diversification of plant megafossils owes more to changing geological conditions than to rapid biological diversification. PMID:10905613

  14. Vascular effects of intermittent hypoxia.

    PubMed

    Kanagy, Nancy L

    2009-01-01

    Obstructive sleep apnea is characterized by repeated upper airway obstruction during sleep and affects between 5% and 20% of the population. Epidemiological studies reveal that sleep apnea and associated intermittent hypoxemia increase the risk for hypertension and vascular disease but the mechanisms underlying these effects are incompletely understood. This review reports the results of rodent models of intermittent hypoxia (IH) and relates them to the observed hemodynamic and vascular consequences of sleep apnea. These animal studies have demonstrated that IH exposure in the absence of any other comorbidity causes hypertension, endothelial dysfunction, and augmented constrictor sensitivity, all due at least in part to increased vascular oxidative stress. Animal studies have used a variety of exposure paradigms to study intermittent hypoxia and these different exposure protocols can cause hypocapnia or hypercapnia-or maintain eucapnia-with accompanying alterations in plasma pH. It appears that these different profiles of arterial blood gases can lead to divergent results but the impact of these differences is still being investigated. Overall, the studies in rodents have clearly demonstrated that the vascular and hemodynamic impact of intermittent hypoxia provides a strong rationale for treating clinical sleep apnea to prevent the resulting cardiovascular morbidity and mortality.

  15. Peripheral vascular imaging and intervention

    SciTech Connect

    Kim, D. ); Orron, D.E. )

    1990-01-01

    This reference addresses the entire clinical approach to the vascular system from the diagnosis of pathology to surgery or interventional radiological management. All diagnostic imaging modalities currently available are included with specific information on how to interpret various results. It features discussions of the latest therapeutic techniques, including laser angioplasty, intravascular stents, and transluminal embolization.

  16. Assessment of vascular effects of tamoxifen and its metabolites on the rat perfused hindquarter vascular bed.

    PubMed

    Montenegro, Marcelo F; Pessa, Lisandra R; Gomes, Valéria A; Desta, Zeruesenay; Flockhart, David A; Tanus-Santos, Jose E

    2009-05-01

    Tamoxifen has been suggested to produce beneficial cardiovascular effects, although the mechanisms for these effects are not fully known. Moreover, although tamoxifen metabolites may exhibit 30-100 times higher potency than the parent drug, no previous study has compared the effects produced by tamoxifen and its metabolites on vascular function. Here, we assessed the vascular responses to acetylcholine and sodium nitroprusside on perfused hindquarter vascular bed of rats treated with tamoxifen or its main metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen, and endoxifen) for 2 weeks. Plasma and whole-blood thiobarbituric acid reactive substances (TBARS) concentrations were determined using a fluorometric method. Plasma nitrite and NOx (nitrite + nitrate) concentrations were determined using an ozone-based chemiluminescence assay and Griess reaction, respectively. Treatment with tamoxifen reduced the responses to acetylcholine (pD(2) = 2.2 +/- 0.06 and 1.9 +/- 0.05 after vehicle and tamoxifen, respectively; P < 0.05), while its metabolites improved these responses (pD(2) = 2.5 +/- 0.04 after N-desmethyl-tamoxifen, 2.5 +/- 0.03 after 4-hydroxy-tamoxifen, and 2.6 +/- 0.08 after endoxifen; P < 0.01). Tamoxifen and its metabolites showed no effect on endothelial-independent responses to sodium nitroprusside (P > 0.05). While tamoxifen treatment resulted in significantly higher plasma and whole blood lipid peroxide levels (37% and 62%, respectively; both P < 0.05), its metabolites significantly decreased lipid peroxide levels (by approximately 50%; P < 0.05). While treatment with tamoxifen decreased the concentrations of markers of nitric oxide formation by approximately 50% (P < 0.05), tamoxifen metabolites had no effect on these parameters (P > 0.05). These results suggest that while tamoxifen produces detrimental effects, its metabolites produce counteracting beneficial effects on the vascular system and on nitric oxide/reactive oxygen species formation. PMID

  17. The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

    PubMed Central

    Hoshi, Ryan A.; Van Lith, Robert; Jen, Michele C.; Allen, Josephine B.; Lapidos, Karen A.; Ameer, Guillermo

    2014-01-01

    Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC–Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC–Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC–Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC–Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC–Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC–Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties. PMID:23069711

  18. Nilotinib-associated vascular events.

    PubMed

    Quintás-Cardama, Alfonso; Kantarjian, Hagop; Cortes, Jorge

    2012-10-01

    Anecdotal evidence suggests that nilotinib therapy may be associated with severe peripheral artery occlusive disease (PAOD). The authors describe the experience at M.D. Anderson Cancer Center regarding vascular events associated with nilotinib therapy in patients with chronic myeloid leukemia. Overall, 5 cases of PAOD were identified among 233 patients, for an incidence of 2%. Nilotinib is a highly selective inhibitor of the inactive conformation of ABL1 kinase. An improved topologic fit to the ABL1 protein-binding surface contributes to its increased potency over imatinib. This higher selectivity in vitro translated to an improved tolerability in vivo. In fact, nilotinib therapy in the frontline phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study was associated with an improved toxicity profile compared with that of imatinib. Intriguingly, several cases of severe peripheral artery occlusive disease (PAOD) have been reported among patients treated with nilotinib in small series. We have identified 5 patients with chronic myeloid leukemia (CML) in whom vascular events developed that were likely related to nilotinib therapy among 233 (2%) patients treated at our institution: 1 patient had recurrent Raynaud syndrome, a second patient had recurrent cerebrovascular accidents, and 3 other patients had PAOD (2 of them with other vascular events, including coronary artery disease and pulmonary emboli, respectively). Risk factors for vascular disease were present in only 1 patient with a history of diabetes mellitus. Although the incidence of vascular events is low, this potential complication should be taken into account when selecting nilotinib for the treatment of CML.

  19. Vascular ageing and interventions: lessons and learnings.

    PubMed

    Williams, Bryan

    2016-06-01

    This review discusses the relationship between elevated blood pressure, hypertension, arterial stiffness and hence vascular ageing. This is a complex process and the majority of treatments target the consequences of this, rather than the pathophysiology of ageing itself. This is because preventing vascular ageing from occurring is complex and would require very early intervention and lifelong treatment. The process of arteriosclerosis is known to result from reversible and irreversible functional components, and, together, these are responsible for the increased systolic and decreased diastolic blood pressure seen with advancing age. Indeed, hypertension develops as it becomes more difficult for the heart to drive blood flow around the body, as a result of poor ventricular coupling and increased arterial stiffness. Elevated blood pressure is therefore a clinical manifestation of ageing that continues to increase with advancing years, and is also linked with an increased risk of cardiac, cerebrovascular and chronic kidney disease. These manifestations arise due to changing haemodynamics associated with ageing, and therefore treatments that reduce the development of these conditions or delay their progression have the potential to improve patient outcomes. This may be possible with existing therapies as well as new treatments currently under investigation.

  20. Vascular Dynamics Aid a Coupled Neurovascular Network Learn Sparse Independent Features: A Computational Model.

    PubMed

    Philips, Ryan T; Chhabria, Karishma; Chakravarthy, V Srinivasa

    2016-01-01

    Cerebral vascular dynamics are generally thought to be controlled by neural activity in a unidirectional fashion. However, both computational modeling and experimental evidence point to the feedback effects of vascular dynamics on neural activity. Vascular feedback in the form of glucose and oxygen controls neuronal ATP, either directly or via the agency of astrocytes, which in turn modulates neural firing. Recently, a detailed model of the neuron-astrocyte-vessel system has shown how vasomotion can modulate neural firing. Similarly, arguing from known cerebrovascular physiology, an approach known as "hemoneural hypothesis" postulates functional modulation of neural activity by vascular feedback. To instantiate this perspective, we present a computational model in which a network of "vascular units" supplies energy to a neural network. The complex dynamics of the vascular network, modeled by a network of oscillators, turns neurons ON and OFF randomly. The informational consequence of such dynamics is explored in the context of an auto-encoder network. In the proposed model, each vascular unit supplies energy to a subset of hidden neurons of an autoencoder network, which constitutes its "projective field." Neurons that receive adequate energy in a given trial have reduced threshold, and thus are prone to fire. Dynamics of the vascular network are governed by changes in the reconstruction error of the auto-encoder network, interpreted as the neuronal demand. Vascular feedback causes random inactivation of a subset of hidden neurons in every trial. We observe that, under conditions of desynchronized vascular dynamics, the output reconstruction error is low and the feature vectors learnt are sparse and independent. Our earlier modeling study highlighted the link between desynchronized vascular dynamics and efficient energy delivery in skeletal muscle. We now show that desynchronized vascular dynamics leads to efficient training in an auto-encoder neural network. PMID

  1. Vascular Dynamics Aid a Coupled Neurovascular Network Learn Sparse Independent Features: A Computational Model

    PubMed Central

    Philips, Ryan T.; Chhabria, Karishma; Chakravarthy, V. Srinivasa

    2016-01-01

    Cerebral vascular dynamics are generally thought to be controlled by neural activity in a unidirectional fashion. However, both computational modeling and experimental evidence point to the feedback effects of vascular dynamics on neural activity. Vascular feedback in the form of glucose and oxygen controls neuronal ATP, either directly or via the agency of astrocytes, which in turn modulates neural firing. Recently, a detailed model of the neuron-astrocyte-vessel system has shown how vasomotion can modulate neural firing. Similarly, arguing from known cerebrovascular physiology, an approach known as “hemoneural hypothesis” postulates functional modulation of neural activity by vascular feedback. To instantiate this perspective, we present a computational model in which a network of “vascular units” supplies energy to a neural network. The complex dynamics of the vascular network, modeled by a network of oscillators, turns neurons ON and OFF randomly. The informational consequence of such dynamics is explored in the context of an auto-encoder network. In the proposed model, each vascular unit supplies energy to a subset of hidden neurons of an autoencoder network, which constitutes its “projective field.” Neurons that receive adequate energy in a given trial have reduced threshold, and thus are prone to fire. Dynamics of the vascular network are governed by changes in the reconstruction error of the auto-encoder network, interpreted as the neuronal demand. Vascular feedback causes random inactivation of a subset of hidden neurons in every trial. We observe that, under conditions of desynchronized vascular dynamics, the output reconstruction error is low and the feature vectors learnt are sparse and independent. Our earlier modeling study highlighted the link between desynchronized vascular dynamics and efficient energy delivery in skeletal muscle. We now show that desynchronized vascular dynamics leads to efficient training in an auto-encoder neural

  2. [Search for Factors Related to Vascular Pain Expression upon Administration of Oxaliplatin into a Peripheral Vein].

    PubMed

    Takagi, Akiko; Yonemoto, Nao; Aoyama, Yuuya; Touma, Yuri; Kajiwara, Michiko; Watanabe, Kosuke; Miyazaki, Yoshiko; Koinuma, Masayoshi

    2015-07-01

    We investigated the relationship between vascular pain and various characteristics (age, sex, cancer stage, performance status [PS], height, weight, body mass index [BMI], body surface area, oxaliplatin dose, and presence and absence of the initial administration of dexamethasone) in colorectal cancer patients who were administered initial doses of oxaliplatin intravenously. The study population included 29 patients treated at Higashi Totsuka Memorial Hospital between June 2010 and April 2014. One-way analysis of variance showed that vascular pain was significantly associated with weight (p=0.015), body surface area (p=0.013), and oxaliplatin doses (p=0.0026), where the significance level was p=0.05. Logistic regression analysis and the likelihood ratio test demonstrated that the likelihood of vascular pain increased with the increase in the oxaliplatin dose. According to the cut-off value of vascular pain determined using the receiver operating characteristic (ROC) analysis, a single dose of oxaliplatin was determined to be 175 mg or more. According to the cut-off value established using the ROC analysis, a single dose of oxaliplatin at which vascular pain is expressed was determined to be 175 mg or more. At this dose, 13 patients complained of vascular pain and 8 did not. At doses less than 175 mg, none of the 8 patients complained of vascular pain. These results suggest that lowering the diluted concentration and reducing the infusion rate of intravenously administered oxaliplatin may reduce vascular pain.

  3. History of vascular access for haemodialysis.

    PubMed

    Konner, Klaus

    2005-12-01

    The history of vascular access is a history of vascular surgery as well as a history of dialysis therapy. This survey is a personal view on the history of vascular access without the ambition to cover every detail, but with an effort to mention the major steps in a fascinating panorama.

  4. Vascular tumors have increased p70 S6-kinase activation and are inhibited by topical rapamycin.

    PubMed

    Du, Wa; Gerald, Damien; Perruzzi, Carole A; Rodriguez-Waitkus, Paul; Enayati, Ladan; Krishnan, Bhuvaneswari; Edmonds, Joseph; Hochman, Marcelo L; Lev, Dina C; Phung, Thuy L

    2013-10-01

    Vascular tumors are endothelial cell neoplasms whose cellular and molecular mechanisms, leading to tumor formation, are poorly understood, and current therapies have limited efficacy with significant side effects. We have investigated mechanistic (mammalian) target of rapamycin (mTOR) signaling in benign and malignant vascular tumors, and the effects of mTOR kinase inhibitor as a potential therapy for these lesions. Human vascular tumors (infantile hemangioma and angiosarcoma) were analyzed by immunohistochemical stains and western blot for the phosphorylation of p70 S6-kinase (S6K) and S6 ribosomal protein (S6), which are activated downstream of mTOR complex-1 (mTORC1). To assess the function of S6K, tumor cells with genetic knockdown of S6K were analyzed for cell proliferation and migration. The effects of topical rapamycin, an mTOR inhibitor, on mTORC1 and mTOR complex-2 (mTORC2) activities, as well as on tumor growth and migration, were determined. Vascular tumors showed increased activation of S6K and S6. Genetic knockdown of S6K resulted in reduced tumor cell proliferation and migration. Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCα, in vascular tumor cells. Rapamycin significantly reduced vascular tumor growth in vitro and in vivo. As a potential localized therapy for cutaneous vascular tumors, topically applied rapamycin effectively reduced tumor growth with limited systemic drug absorption. These findings reveal the importance of mTOR signaling pathways in benign and malignant vascular tumors. The mTOR pathway is an important therapeutic target in vascular tumors, and topical mTOR inhibitors may provide an alternative and well-tolerated therapy for the treatment of cutaneous vascular lesions. PMID:23938603

  5. ISH PRE-2 THE VASCULAR PHENOTYPE IN HYPERTENSION - MOLECULAR MECHANISMS AND CLINICAL IMPLICATIONS.

    PubMed

    Touyz, Rhian M

    2016-09-01

    Pathophysiological mechanisms contributing to hypertension include endothelial dysfunction and vascular ignalling. These changes are initially adaptive but chronically become maladaptive leading to vascular damage and loss of function. Common to these processes are changes in the characteristics of vascular cells to a pro-infl ammatory, vasoconstrictory and proliferative phenotype, infl uenced by activation of the RAS and oxidative stress. Increased ROS production and decreased cellular antioxidant defense mechanisms, contribute to oxidative stress, which infl uences redox-sensitive Ang II ignalling that promotes vascular injury in hypertension. Clinical studies demonstrate that improved vascular function is associated with reduced hypertension-related target-organ damage. Accordingly approaches to promote vascular health should be a therapeutic priority. Such strategies include conventional antihypertensive drugs and lifestyle modifi cations, which reduce oxidative stress and dampen activation of injurious ignalling pathways. Novel approaches, such as Nox inhibitors, agents that increase antioxidant capacity (e.g. Nrf-2 activators), anti-infl ammatory immune-modulators and elements of counter-regulatory axis of the RAS, namely AT2R, Ang-(1-7) and Mas receptors, have potential in promoting vascular health and reducing blood pressure. This presentation highlights some molecular and cellular mechanisms that underlie vascular injury in hypertension, and focuses on strategies to ameliorate vascular damage. Novel concepts relating to redox ignalling will be discussed. By elucidating sub-cellular mechanisms new disease-specifi c vascular molecules will be identifi ed for development of innovative therapies to prevent/regress injury and thereby improve management of hypertension and associated target organ damage. PMID:27643158

  6. Vascular diseases: aortitis, aortic aneurysms, and vascular calcification.

    PubMed

    Ladich, Elena; Yahagi, Kazuyuki; Romero, Maria E; Virmani, Renu

    2016-01-01

    Inflammatory diseases of the aorta broadly include noninfectious and infectious aortitis, periaortitis, atherosclerosis, and inflammatory atherosclerotic aneurysms. Aortitis is uncommon but is increasingly recognized as an important cause of aortic aneurysms and dissections. Abdominal (AAA) and thoracic aortic aneurysms (TAA) have different pathologies and etiologies. AAAs are the most common type of aortic aneurysm, and the vast majority of these are atherosclerotic. The causes of TAA vary depending on the site of involvement, but medial degeneration is a common pathologic substrate, regardless of etiology, and genetic influences play a prominent role in TAA expression. Standardized classification schemes for inflammatory and degenerative diseases of the aorta have only recently been added to the pathology literature. A brief overview of the new histopathologic classifications for aortic inflammatory and degenerative diseases has recently been published by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology as a consensus document on the surgical pathology of the aorta. Vascular calcification is a highly regulated biologic process, and the mechanisms leading to vascular calcification are under investigation. Calcification may occur in the intima (atherosclerotic) or in the media secondary to metabolic disease. Rarely, vascular calcification may be associated with genetic disorders. PMID:27526100

  7. Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease

    PubMed Central

    Ackers-Johnson, Matthew; Talasila, Amarnath; Sage, Andrew P; Long, Xiaochun; Bot, Ilze; Morrell, Nicholas W; Bennett, Martin R; Miano, Joseph M.; Sinha, Sanjay

    2015-01-01

    Objective Atherosclerosis, the cause of 50% of deaths in westernised societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local pro-inflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response. Approach and Results We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic ApoE−/− mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation. Conclusions We propose myocardin as a guardian of the contractile, non-inflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease. PMID:25614278

  8. Carbon monoxide effects on calcium levels in vascular smooth muscle

    SciTech Connect

    Lin, H.; McGrath, J.J.

    1988-01-01

    Previously the authors showed that carbon monoxide (CO) relaxes vascular smooth muscle in the working heart and thoracic aorta preparation perfused with hemoglobin-free, Krebs-Henseleit (KH) solution. The CO-induced relaxation was not caused by hypoxia, nor was it mediated by adrenergic influences, adenosine, or prostaglandins. In these studies the effect of CO on calcium (Ca/sup + +/) concentrations in vascular smooth muscle was determined using /sup 45/Ca as a tracer. Isolated rat thoracic aorta segments were incubated with /sup 45/Ca and gassed with O/sub 2/, N/sub 2/, or CO for 60 min. Verapamil was used to verify the effectiveness of the test system. Ca/sup + +/ concentrations were 488 /+ -/ 35 and 515 /+ -/ 26 mM/g tissue (X /+ -/ SE) in aortic rings gassed with O/sub 2/ and N/sub 2/, respectively. CO reduced Ca/sup + +/ concentrations significantly (P<0.01) by 29% to 369 /+ -/ 18 mM/g tissue. Verapamil treatment reduced Ca/sup + +/ concentrations by 40% to 314 /+ -/ 23 mM/g tissue. These results suggest that CO relaxes vascular smooth muscle and dilates blood vessels by decreasing Ca/sup + +/ concentrations in vascular smooth muscle.

  9. Ca(2+) handling alterations and vascular dysfunction in diabetes.

    PubMed

    Fernández-Velasco, María; Ruiz-Hurtado, Gema; Gómez, Ana M; Rueda, Angélica

    2014-11-01

    More than 65% of patients with diabetes mellitus die from cardiovascular disease or stroke. Hyperglycemia, due to either reduced insulin secretion or reduced insulin sensitivity, is the hallmark feature of diabetes mellitus. Vascular dysfunction is a distinctive phenotype found in both types of diabetes and could be responsible for the high incidence of stroke, heart attack, and organ damage in diabetic patients. In addition to well-documented endothelial dysfunction, Ca(2+) handling alterations in vascular smooth muscle cells (VSMCs) play a key role in the development and progression of vascular complications in diabetes. VSMCs provide not only structural integrity to the vessels but also control myogenic arterial tone and systemic blood pressure through global and local Ca(2+) signaling. The Ca(2+) signalosome of VSMCs is integrated by an extensive number of Ca(2+) handling proteins (i.e. channels, pumps, exchangers) and related signal transduction components, whose function is modulated by endothelial effectors. This review summarizes recent findings concerning alterations in endothelium and VSMC Ca(2+) signaling proteins that may contribute to the vascular dysfunction found in the diabetic condition.

  10. Intraoperative neuromonitoring in major vascular surgery.

    PubMed

    So, V C; Poon, C C M

    2016-09-01

    There has been a growing interest in using intraoperative neuromonitoring to reduce the incidence of stroke and paralysis in major vascular interventions. Electroencephalography, various neurophysiological evoked potential measurements, transcranial Doppler, and near-infrared spectroscopy are some of the modalities currently used to detect neural injuries. A good understanding of these modalities and their interactions with anaesthesia is important to maximize their value and to allow meaningful interpretation of their results. In view of the inter-individual differences in anatomy, physiological reserves, and severity of pathological processes, neuromonitoring may be a valuable method to evaluate the well-being of the nervous system during and after surgical interventions. In this review, we summarize some of their applications, efficacies, and drawbacks in major carotid and aortic surgeries. PMID:27566804

  11. [Minimally invasive operations in vascular surgery].

    PubMed

    Stádler, Petr; Sedivý, Petr; Dvorácek, Libor; Slais, Marek; Vitásek, Petr; El Samman, Khaled; Matous, Pavel

    2011-01-01

    Minimally invasive surgery provides an attractive alternative compared with conventional surgical approaches and is popular with patients, particularly because of its favourable cosmetic results. Vascular surgery has taken its inspiration from general surgery and, over the past few years, has also been reducing the invasiveness of its operating methods. In addition to traditional laparoscopic techniques, we most frequently encounter the endovascular treatment of aneurysms of the thoracic and abdominal aorta and, most recently, robot-assisted surgery in the area of the abdominal aorta and pelvic arteries. Minimally invasive surgical interventions also have other advantages, including less operative trauma, a reduction in post-operative pain, shorter periods spent in the intensive care unit and overall hospitalization times, an earlier return to normal life and, finally, a reduction in total treatment costs.

  12. Akt isoforms in vascular disease.

    PubMed

    Yu, Haixiang; Littlewood, Trevor; Bennett, Martin

    2015-08-01

    The mammalian serine/threonine Akt kinases comprise three closely related isoforms: Akt1, Akt2 and Akt3. Akt activation has been implicated in both normal and disease processes, including in development and metabolism, as well as cancer and cardiovascular disease. Although Akt signalling has been identified as a promising therapeutic target in cancer, its role in cardiovascular disease is less clear. Importantly, accumulating evidence suggests that the three Akt isoforms exhibit distinct tissue expression profiles, localise to different subcellular compartments, and have unique modes of activation. Consistent with in vitro findings, genetic studies in mice show distinct effects of individual Akt isoforms on the pathophysiology of cardiovascular disease. This review summarises recent studies of individual Akt isoforms in atherosclerosis, vascular remodelling and aneurysm formation, to provide a comprehensive overview of Akt function in vascular disease.

  13. Akt isoforms in vascular disease

    PubMed Central

    Yu, Haixiang; Littlewood, Trevor; Bennett, Martin

    2015-01-01

    The mammalian serine/threonine Akt kinases comprise three closely related isoforms: Akt1, Akt2 and Akt3. Akt activation has been implicated in both normal and disease processes, including in development and metabolism, as well as cancer and cardiovascular disease. Although Akt signalling has been identified as a promising therapeutic target in cancer, its role in cardiovascular disease is less clear. Importantly, accumulating evidence suggests that the three Akt isoforms exhibit distinct tissue expression profiles, localise to different subcellular compartments, and have unique modes of activation. Consistent with in vitro findings, genetic studies in mice show distinct effects of individual Akt isoforms on the pathophysiology of cardiovascular disease. This review summarises recent studies of individual Akt isoforms in atherosclerosis, vascular remodelling and aneurysm formation, to provide a comprehensive overview of Akt function in vascular disease. PMID:25929188

  14. Locally vascularized pelvic accessory spleen.

    PubMed

    Iorio, F; Frantellizzi, V; Drudi, Francesco M; Maghella, F; Liberatore, M

    2016-01-01

    Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.

  15. Vascular Pathophysiology in Hearing Disorders

    PubMed Central

    Trune, Dennis R.; Nguyen-Huynh, Anh

    2014-01-01

    The inner ear vasculature is responsible for maintenance of the blood-labyrinth barrier, transport of systemic hormones for ion homeostasis, and supplying nutrients for metabolic functions. Unfortunately, these blood vessels also expose the ear to circulating inflammatory factors resulting from systemic diseases. Thus, while the inner ear blood vessels are critical for normal function, they also are facilitating pathologic mechanisms that result in hearing and vestibular dysfunction. In spite of these numerous critical roles of inner ear vasculature, little is known of its normal homeostatic functions and how these are compromised in disease. The objective of this review is to discuss the current concepts of vascular biology, how blood vessels naturally respond to circulating inflammatory factors, and how such mechanisms of vascular pathophysiology may cause hearing loss. PMID:25346568

  16. Metoclopramide and renal vascular resistance.

    PubMed

    Manara, A R; Bolsin, S; Monk, C R; Hartnell, G; Harris, R A

    1991-01-01

    We have studied the effect of i.v. metoclopramide on renal vascular resistance in nine healthy volunteers. Peak systolic and end-diastolic frequencies were measured using duplex Doppler ultrasound of a renal interlobar artery, before and after the administration of i.v. metoclopramide 10 mg, and the resistance index derived. There was no significant change in mean arterial pressure or resistance index following metoclopramide.

  17. Vascular compression of the duodenum.

    PubMed Central

    Moskovich, R; Cheong-Leen, P

    1986-01-01

    Compression of the third or fourth part of the duodenum by the superior mesenteric artery or one of its branches is the anatomic basis for some cases of duodenal obstruction. Two cases of vascular obstruction of the duodenum after surgical correction of scoliosis are presented. The embryologic and pathoanatomic bases for this condition, and the rationale for treatment, are described. Images Figure 1. Figure 2. Figure 3. PMID:3761291

  18. Metoclopramide and renal vascular resistance.

    PubMed

    Manara, A R; Bolsin, S; Monk, C R; Hartnell, G; Harris, R A

    1991-01-01

    We have studied the effect of i.v. metoclopramide on renal vascular resistance in nine healthy volunteers. Peak systolic and end-diastolic frequencies were measured using duplex Doppler ultrasound of a renal interlobar artery, before and after the administration of i.v. metoclopramide 10 mg, and the resistance index derived. There was no significant change in mean arterial pressure or resistance index following metoclopramide. PMID:1997046

  19. [Jaboulay, vascular surgeon at Lyon].

    PubMed

    Bouchet, Mathieu

    2010-01-01

    Mathieu Jaboulay was an excellent surgeon. He was the first to come up with the principles of vascular surgery as he made a surgical anastomosis between two arteries of a dog by an eversion circular suture. In 1902, he implemented a suture between an artery and a vein in an arteritis by obliteration. Jaboulay also tried the graft of an animal kidney on the crease of a human elbow in 1906. Jaboulay was an initiator for Alexis Carrel. PMID:20527332

  20. The European experience with vascular injuries.

    PubMed

    Fingerhut, Abe; Leppäniemi, Ari K; Androulakis, George A; Archodovassilis, F; Bouillon, Bertil; Cavina, Enrico; Chaloner, Eddie; Chiarugi, Massimo; Davidovic, Lazar; Delgado-Millan, Miguel Angel; Goris, Jan; Gunnlaugsson, Gunnar H; Jover, Jose Maria; Konstandoulakis, Manoussos M; Kurtoglu, Mehmet; Lepäntalo, Mauri; Llort-Pont, Carme; Meneu-Diaz, Juan Carlos; Moreno-Gonzales, Enrique; Navarro-Soto, Salvador; Panoussis, P; Ryan, James M; Salenius, Juha P; Seccia, Massimo; Takolander, Rabbe; Taviloglu, Korhan; Tiesenhausen, Kurt; Torfason, Bjarni; Uranüs, Selman

    2002-02-01

    The rich and diverse heritage of the management of vascular injuries in the 45 independent European countries prevents the authors from revealing a uniform picture of the European experience, but some trends are clearly emerging. In countries with a low incidence of penetrating trauma and increasing use of interventional vascular procedures, the proportion of iatrogenic vascular trauma exceeds 40% of all vascular injuries, whereas on other parts of the continent, armed conflicts are still a major cause of vascular trauma. National vascular registries, mostly in the Scandinavian countries, produce useful, nationwide data about vascular trauma and its management but suffer still from inadequate data collection. Despite a relatively low incidence of vascular trauma in most European countries, the results are satisfactory, probably in most cases because of active and early management by surgeons on call, whether with vascular training or not, treating all kinds of vascular surgical emergencies. In some countries, attempts at developing a trauma and emergency surgical specialty, including expertise in the management of vascular injuries, are on their way. PMID:11905944

  1. The European experience with vascular injuries.

    PubMed

    Fingerhut, Abe; Leppäniemi, Ari K; Androulakis, George A; Archodovassilis, F; Bouillon, Bertil; Cavina, Enrico; Chaloner, Eddie; Chiarugi, Massimo; Davidovic, Lazar; Delgado-Millan, Miguel Angel; Goris, Jan; Gunnlaugsson, Gunnar H; Jover, Jose Maria; Konstandoulakis, Manoussos M; Kurtoglu, Mehmet; Lepäntalo, Mauri; Llort-Pont, Carme; Meneu-Diaz, Juan Carlos; Moreno-Gonzales, Enrique; Navarro-Soto, Salvador; Panoussis, P; Ryan, James M; Salenius, Juha P; Seccia, Massimo; Takolander, Rabbe; Taviloglu, Korhan; Tiesenhausen, Kurt; Torfason, Bjarni; Uranüs, Selman

    2002-02-01

    The rich and diverse heritage of the management of vascular injuries in the 45 independent European countries prevents the authors from revealing a uniform picture of the European experience, but some trends are clearly emerging. In countries with a low incidence of penetrating trauma and increasing use of interventional vascular procedures, the proportion of iatrogenic vascular trauma exceeds 40% of all vascular injuries, whereas on other parts of the continent, armed conflicts are still a major cause of vascular trauma. National vascular registries, mostly in the Scandinavian countries, produce useful, nationwide data about vascular trauma and its management but suffer still from inadequate data collection. Despite a relatively low incidence of vascular trauma in most European countries, the results are satisfactory, probably in most cases because of active and early management by surgeons on call, whether with vascular training or not, treating all kinds of vascular surgical emergencies. In some countries, attempts at developing a trauma and emergency surgical specialty, including expertise in the management of vascular injuries, are on their way.

  2. [Vascular Ehlers-Danlos syndrome and pregnancy: an obstetrical specific support].

    PubMed

    Jamard, A; Le Hello, C; Simonet, T; Dreyfus, M

    2012-11-01

    The Ehlers-Danlos syndrome (EDS) is a rare inheritable disease, characterised by a defect in collagen synthesis. Various types have been described and the type IV or vascular type is the most severe characterised by vascular, gastrointestinal and gynaecologic complications. We describe in a case report the specific obstetrical support we applied to avoid the most frequent complications such as early spontaneous abortions, pre-term delivery, tearing of perineum, uterine and vascular rupture and hard healing. Pregnancy is very risky in women with vascular EDS. Combination of multidisciplinary support and advice of the rare vascular disease national reference centre may reduce the morbi-mortality rate, including celiprolol long-term treatment.

  3. Vascular calcification in rheumatoid arthritis: prevalence, pathophysiological aspects and potential targets.

    PubMed

    Paccou, J; Brazier, M; Mentaverri, R; Kamel, S; Fardellone, P; Massy, Z A

    2012-10-01

    Individuals with rheumatoid arthritis (RA) are at increased risk for morbidity and mortality from cardiovascular disease. Excess cardiovascular mortality in RA patients cannot be fully explained by conventional cardiovascular risk factors. The purpose of this review is to discuss recent progress concerning the prevalence and pathophysiological aspects of vascular calcification in RA. RA patients have early-onset diffuse calcification involving multiple vascular beds compared to age and sex-matched controls. Pathogenesis of vascular calcification in RA patients is not fully understood, but specific mediators such as proinflammatory cytokines and not global inflammation could be involved. The possible link between osteoporosis and vascular calcification in RA will not be discussed. Finally, potential targets to reduce vascular calcification in RA will be discussed.

  4. Mechanosensing at the Vascular Interface

    PubMed Central

    Tarbell, John M.; Simon, Scott I.; Curry, Fitz-Roy E.

    2015-01-01

    Mammals are endowed with a complex set of mechanisms that sense mechanical forces imparted by blood flow to endothelial cells (ECs), smooth muscle cells, and circulating blood cells to elicit biochemical responses through a process referred to as mechanotransduction. These biochemical responses are critical for a host of other responses, including regulation of blood pressure, control of vascular permeability for maintaining adequate perfusion of tissues, and control of leukocyte recruitment during immunosurveillance and inflammation. This review focuses on the role of the endothelial surface proteoglycan/glycoprotein layer—the glycocalyx (GCX)—that lines all blood vessel walls and is an agent in mechanotransduction and the modulation of blood cell interactions with the EC surface. We first discuss the biochemical composition and ultrastructure of the GCX, highlighting recent developments that reveal gaps in our understanding of the relationship between composition and spatial organization. We then consider the roles of the GCX in mechanotransduction and in vascular permeability control and review the prominent interaction of plasma borne sphingosine-1 phosphate (S1P), which has been shown to regulate both the composition of the GCX and the endothelial junctions. Finally, we consider the association of GCX degradation with inflammation and vascular disease and end with a final section on future research directions. PMID:24905872

  5. [Vascular Ehlers-Danlos syndrome].

    PubMed

    Frank, Michael

    2009-04-20

    Vascular type Ehlers-Danlos syndrome (EDS) is a rare inherited disease with an autosomal dominant trait. The mutation of the COL3A1 gene which encodes type III collagen, is responsible of early vascular (spontaneous arterial rupture or dissection), digestive (perforation) and obstetrical events (uterine and arterial rupture). Diagnosis of the disease is primarily clinical, especially in case of characteristic morphologic features. Diagnostic certainty is obtained by evidencing the mutation of the COL3A1 gene. Some arterial lesions are suggestive of the disease, as dissecting aneurysms of the internal carotid, of the iliac arteries, and of the anterior visceral aortic branches, fusiform aneurisms of the splenic artery, and the occurrence of a non traumatic direct carotid-cavernous fistula. The occurrence of a spontaneous peritonitis or of an extensive perineal tear after delivery should also draw physician's attention. Because of the unpredictability of arterial or organ rupture, any patient diagnosed with vascular type EDS presenting with an acute pain syndrome should be considered as a trauma situation and be investigated straightaway by CT-scan or MRI testing, in order to eliminate a life threatening complication. PMID:19462862

  6. [Vascular dementia: facts and controversies].

    PubMed

    Pavlović, Aleksandra; Pavlović, Dragan; Aleksić, Vuk; Sternić, Nadezda

    2013-01-01

    Vascular dementia (VaD) is the second most frequent dementia after Alzheimer's disease, and is diagnosed during lifetime in 20% of demented patients. Five-year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors forVaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step-by-step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class Ila recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer's disease dementia. PMID:23745353

  7. Pregnancy and Vascular Liver Disease

    PubMed Central

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-01-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd–Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  8. Does the use of primary continuous positive airway pressure reduce the need for intubation and mechanical ventilation in infants ≤32 weeks’ gestation?

    PubMed Central

    Yee, Wendy H; Scotland, Jeanne; Pham, Yung; Finch, Robert

    2011-01-01

    BACKGROUND: Ventilator-induced lung injury is a recognized risk factor for bronchopulmonary dysplasia. OBJECTIVE: To determine whether primary continuous positive airway pressure (CPAP), defined as CPAP without previous endotracheal intubation for any indication, can reduce the need for intubation and mechanical ventilation in infants born at ≤32 weeks’ gestational age. METHODS: The literature was reviewed using the methodology for systematic reviews for the Consensus on Resuscitation Science adapted from the American Heart Association’s International Liaison Committee on Resuscitation. RESULTS: Fourteen studies were reviewed. Eleven studies provided varying degrees of supportive evidence (level of evidence 3 to 4) that the use of primary CPAP can reduce the need for intubation and mechanical ventilation. CONCLUSION: The use of CPAP as a primary intervention and mode of respiratory support is an option for infants ≤32 weeks’ gestation, but avoidance of intubation and mechanical ventilation is more likely in mature infants >27 weeks’ gestation. PMID:23204903

  9. Retinal Vascular Fractals and Cognitive Impairment

    PubMed Central

    Ong, Yi-Ting; Hilal, Saima; Cheung, Carol Yim-lui; Xu, Xin; Chen, Christopher; Venketasubramanian, Narayanaswamy; Wong, Tien Yin; Ikram, Mohammad Kamran

    2014-01-01

    Background Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia. Methods This is a cross-sectional study of 300 Chinese participants (age: ≥60 years) from the ongoing Epidemiology of Dementia in Singapore study who underwent detailed clinical examinations including retinal photography, brain imaging and neuropsychological testing. Retinal vascular parameters were assessed from optic disc-centered photographs using a semiautomated program. A comprehensive neuropsychological battery was administered, and cognitive function was summarized as composite and domain-specific Z-scores. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to standard diagnostic criteria. Results Among 268 eligible nondemented participants, 78 subjects were categorized as CIND-mild and 69 as CIND-moderate. In multivariable adjusted models, reduced retinal arteriolar and venular fractal dimensions were associated with an increased risk of CIND-mild and CIND-moderate. Reduced fractal dimensions were associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed. Conclusion A sparser retinal microvascular network, represented by reduced arteriolar and venular fractal dimensions, was associated with cognitive impairment, suggesting that early microvascular damage may be present in preclinical stages of dementia. PMID:25298774

  10. Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage.

    PubMed

    Jeong, Ji Hoon; Nguyen, Hong Khanh; Lee, Jung Eun; Suh, Wonhee

    2016-01-01

    Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood-retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. PMID:27462154

  11. Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

    PubMed Central

    Jeong, Ji Hoon; Nguyen, Hong Khanh; Lee, Jung Eun; Suh, Wonhee

    2016-01-01

    Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. PMID:27462154

  12. Low matrix metalloproteinase levels precede vascular lesion formation in the JCR:LA-cp rat.

    PubMed

    Wilson, David; Massaeli, Hamid; Russell, James C; Pierce, Grant N; Zahradka, Peter

    2003-07-01

    Clinically significant occlusive vascular lesions contain more extracellular matrix (ECM) proteins and lipid deposition than healthy vascular tissue. The events leading to this condition remain unresolved. One possibility is that ECM deposition may exceed ECM degradation which would contribute to the expansion of the vascular lesion. Utilizing lean (+/?) and insulin-resistant, corpulent (cp/cp) JCR:LA-cp rats, which are predisposed to develop vascular lesions, we have compared the matrix metalloproteinase (MMP) profile prior to the development of significant vascular lesions. Analysis of serum MMPs revealed that cp/cp rats have lower circulating levels than (+/?) controls. This is observed prior to the development of any noticeable atherosclerotic lesions. It also occurs as the hyperinsulinemia and insulin resistance is first developing in these rats. Female corpulent animals, which are less prone to develop vascular lesions, also exhibit a depressed serum MMP profile of a similar magnitude to their male counterparts. Primary vascular smooth muscle cells isolated from cp/cp animals also showed a reduction in secreted MMP compared with cells derived from +/? lean controls. We conclude that reduced MMP levels could lead to increased ECM accumulation and thus contribute to early vascular lesion formation.

  13. The primary vascular dysregulation syndrome: implications for eye diseases

    PubMed Central

    2013-01-01

    Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood–brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide

  14. Evaluation of Staphylococcus aureus Eradication Therapy in Vascular Surgery

    PubMed Central

    Donker, J. M. W.; van Rijen, M. M. L.; Kluytmans, J. A. J. W.; van der Laan, L.

    2016-01-01

    Introduction Surgical site infections (SSI) are a serious complication in vascular surgery which may lead to severe morbidity and mortality. Staphylococcus aureus nasal carriage is associated with increased risk for development of SSIs in central vascular surgery. The risk for SSI can be reduced by perioperative eradication of S. aureus carriage in cardiothoracic and orthopedic surgery. This study analyzes the relation between S. aureus eradication therapy and SSI in a vascular surgery population. Methods A prospective cohort study was performed, including all patients undergoing vascular surgery between February 2013 and April 2015. Patients were screened for S. aureus nasal carriage and, when tested positive, were subsequently treated with eradication therapy. The presence of SSI was recorded based on criteria of the CDC. The control group consisted of a cohort of vascular surgery patients in 2010, who were screened, but received no treatment. Results A total of 444 patients were screened. 104 nasal swabs were positive for S. aureus, these patients were included in the intervention group. 204 patients were screened in the 2010 cohort. 51 tested positive and were included in the control group. The incidence of S. aureus infection was 5 out of 51 (9.8%) in the control group versus 3 out of 104 in the eradication group (2.2%; 95% confidence interval 0.02–1.39; P = 0.13). A subgroup analysis showed that the incidence of S. aureus infection was 3 out of 23 (13.0%) in the control group in central reconstructive surgery versus 0 out of 44 in the intervention group (P = 0.074). The reduction of infection pressure by S. aureus was stronger than the reduction of infection pressure by other pathogens (exact maximum likelihood estimation; OR = 0.0724; 95% CI: 0.001–0.98; p = 0.0475). Conclusion S. aureus eradication therapy reduces the infection pressure of S. aureus, resulting in a reduction of SSIs caused by S. aureus. PMID:27529551

  15. Methicillin-resistant Staphylococcus aureus infection in vascular surgical patients.

    PubMed Central

    Murphy, G. J.; Pararajasingam, R.; Nasim, A.; Dennis, M. J.; Sayers, R. D.

    2001-01-01

    BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is emerging as a major problem in vascular surgical practice. The aim of this study was to review the management of patients with MRSA infection complicating vascular surgical operations. METHODS: Data were obtained from the vascular audit, case notes, intensive therapy unit (ITU) notes, high dependency unit (HDU) notes and microbiological records of patients who underwent either arterial reconstruction (n = 464) or limb amputation (n = 110) between April 1994 and October 1998. RESULTS: Forty-nine vascular surgical patients developed clinical MRSA infection (9%). Clinical MRSA infection in patients who had undergone aorto-iliac reconstruction (n = 18) was associated with a 56% mortality (n = 10) and the most common infections were bacteraemia (55%) and pneumonia (50%). MRSA infection occurred in 17 patients who had undergone infra-inguinal bypass and was associated with a 29% mortality (n = 5). The most common site of MRSA infection was the groin wound (76%) leading to anastomotic dehiscence and death in one patient (11%) and necessitating wound debridement in 4 patients (22%). MRSA infection of the groin wound in the presence of a prosthetic graft (n = 3) led to anastomotic dehiscence in 2 patients, and graft excision in 2 patients. Similar complications were not observed in the presence of an underlying autogeneous long saphenous vein graft (n = 16). MRSA infection following major lower limb amputation (n = 14) was associated with death in 5 patients (36%). Wound infection in 10 amputees (71%) led to revision of the amputation to a higher level in 2 (14%) and wound debridement in 2 (14%). CONCLUSIONS: MRSA infection has a high mortality in vascular surgical patients in general, and following aorto-iliac reconstruction in particular. Autogeneous vein may confer some protection against local complications following groin wound infection. Strategies aimed at reducing the incidence of infection

  16. Cell-based strategies for vascular regeneration.

    PubMed

    Zou, Tongqiang; Fan, Jiabing; Fartash, Armita; Liu, Haifeng; Fan, Yubo

    2016-05-01

    Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ. PMID:26864677

  17. Potential benefits of exercise on blood pressure and vascular function.

    PubMed

    Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

    2013-01-01

    Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function.

  18. Management of retinal vascular diseases: a patient-centric approach

    PubMed Central

    Brand, C S

    2012-01-01

    Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases. PMID:22495396

  19. Kruppel-like factor 15 is critical for vascular inflammation

    PubMed Central

    Lu, Yuan; Zhang, Lisheng; Liao, Xudong; Sangwung, Panjamaporn; Prosdocimo, Domenick A.; Zhou, Guangjin; Votruba, Alexander R.; Brian, Leigh; Han, Yuh Jung; Gao, Huiyun; Wang, Yunmei; Shimizu, Koichi; Weinert-Stein, Kaitlyn; Khrestian, Maria; Simon, Daniel I.; Freedman, Neil J.; Jain, Mukesh K.

    2013-01-01

    Activation of cells intrinsic to the vessel wall is central to the initiation and progression of vascular inflammation. As the dominant cellular constituent of the vessel wall, vascular smooth muscle cells (VSMCs) and their functions are critical determinants of vascular disease. While factors that regulate VSMC proliferation and migration have been identified, the endogenous regulators of VSMC proinflammatory activation remain incompletely defined. The Kruppel-like family of transcription factors (KLFs) are important regulators of inflammation. In this study, we identified Kruppel-like factor 15 (KLF15) as an essential regulator of VSMC proinflammatory activation. KLF15 levels were markedly reduced in human atherosclerotic tissues. Mice with systemic and smooth muscle–specific deficiency of KLF15 exhibited an aggressive inflammatory vasculopathy in two distinct models of vascular disease: orthotopic carotid artery transplantation and diet-induced atherosclerosis. We demonstrated that KLF15 alters the acetylation status and activity of the proinflammatory factor NF-κB through direct interaction with the histone acetyltransferase p300. These studies identify a previously unrecognized KLF15-dependent pathway that regulates VSMC proinflammatory activation. PMID:23999430

  20. Management of retinal vascular diseases: a patient-centric approach.

    PubMed

    Brand, C S

    2012-04-01

    Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases.

  1. Vascular Ageing and Exercise: Focus on Cellular Reparative Processes

    PubMed Central

    Ross, Mark D.; Malone, Eva; Florida-James, Geraint

    2016-01-01

    Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with “vascular ageing” and are often accompanied by a reduced ability for the body to repair vascular damage, termed “reendothelialization.” Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this “vascular ageing” process. PMID:26697131

  2. Vascular thalamic amnesia: a reappraisal.

    PubMed

    Carlesimo, Giovanni Augusto; Lombardi, Maria Giovanna; Caltagirone, Carlo

    2011-04-01

    In humans lacunar infarcts in the mesial and anterior regions of the thalami are frequently associated with amnesic syndromes. In this review paper, we scrutinized 41 papers published between 1983 and 2009 that provided data on a total of 83 patients with the critical ischemic lesions (i.e. 17 patients with right-sided lesions, 25 with left-sided lesions and 41 with bilateral lesions). We aimed to find answers to the following questions concerning the vascular thalamic amnesia syndrome: (i) Which qualitative pattern of memory impairment (and associated cognitive and behavioral deficits) do these patients present? (ii) Which lesioned intrathalamic structures are primarily responsible for the amnesic syndrome? (iii) Are the recollection and familiarity components of declarative memory underlain by the same or by different thalamic structures? Results of the review indicate that, similar to patients with amnesic syndromes due to mesio-temporal lobe damage, patients with vascular thalamic amnesia display a prevalent deficit of declarative anterograde long-term memory, a less consistent deficit of declarative retrograde long-term memory and substantially spared short-term and implicit memory. Unlike mesio-temporal lobe patients, however, vascular thalamic amnesics often present dysexecutive and behavioral deficits similar to those observed in patients with frontal damage. The presence of an amnesic syndrome in patients with thalamic lacunar infarcts is strongly predicted by involvement of the mammillo-thalamic tract, which connects the anterior nuclei complex to the hippocampus proper via the fornix and the mammillary bodies. Finally, data reported in a few single cases provide support for the hypothesis that thalamic regions connected to distinct areas of the mesio-temporal lobe play differential roles in recollection and familiarity processes. The mammillo-thalamic tract/anterior nuclei axis seems primarily implicated in recollective processes, whereas the

  3. Endurance exercise attenuates ventilator-induced diaphragm dysfunction.

    PubMed

    Smuder, Ashley J; Min, Kisuk; Hudson, Matthew B; Kavazis, Andreas N; Kwon, Oh-Sung; Nelson, W Bradley; Powers, Scott K

    2012-02-01

    Controlled mechanical ventilation (MV) is a life-saving measure for patients in respiratory failure. However, MV renders the diaphragm inactive leading to diaphragm weakness due to both atrophy and contractile dysfunction. It is now established that oxidative stress is a requirement for MV-induced diaphragmatic proteolysis, atrophy, and contractile dysfunction to occur. Given that endurance exercise can elevate diaphragmatic antioxidant capacity and the levels of the cellular stress protein heat shock protein 72 (HSP72), we hypothesized that endurance exercise training before MV would protect the diaphragm against MV-induced oxidative stress, atrophy, and contractile dysfunction in female Sprague-Dawley rats. Our results confirm that endurance exercise training before MV increased both HSP72 and the antioxidant capacity in the diaphragm. Importantly, compared with sedentary animals, exercise training before MV protected the diaphragm against MV-induced oxidative damage, protease activation, myofiber atrophy, and contractile dysfunction. Further, exercise protected diaphragm mitochondria against MV-induced oxidative damage and uncoupling of oxidative phosphorylation. These results provide the first evidence that exercise can provide protection against MV-induced diaphragm weakness. These findings are important and establish the need for future experiments to determine the mechanism(s) responsible for exercise-induced diaphragm protection.

  4. Major vascular injuries complicating knee arthroscopy

    PubMed Central

    Bancu, Serban; Muresan, Mircea; Sala, Daniela

    2015-01-01

    Starting with a case report, we made a detailed review of the literature, with the purpose of identifying and analyzing the type of iatrogenic vascular lesion following knee arthroscopy and the method of vascular repair. A PubMed literature search was undertaken to locate all reported cases of major vascular iatrogenic injuries during arthroscopic knee procedures. We identified 39 papers which report a total of 62 cases of major iatrogenic popliteal lesions after knee arthroscopy, between 1985 and 2014. The type of arthroscopic intervention performed, the type of iatrogenic vascular lesion encountered, the time passed until its discovery and treatment, the method of vascular reconstruction, and the postoperative course are presented. Postarthroscopy vascular complications are infrequent but potentially disastrous for the condition of the affected inferior limb. An early diagnosis and reintervention are mandatory for a good postoperative outcome. PMID:26240627

  5. DNA Damage and Repair in Vascular Disease.

    PubMed

    Uryga, Anna; Gray, Kelly; Bennett, Martin

    2016-01-01

    DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Such DNA repair mechanisms either stall the cell cycle to allow repair to occur or trigger apoptosis or cell senescence to prevent propagation of damaged DNA. Recent evidence has indicated that DNA damage occurs early, is progressive, and is sufficient to impair function of cells composing the vascular wall. The consequences of persistent genomic and mitochondrial DNA damage, including inflammation, cell senescence, and apoptosis, are present in vascular disease. DNA damage can thus directly cause vascular disease, opening up new possibilities for both prevention and treatment. We review the evidence for and the causes, types, and consequences of DNA damage in vascular disease.

  6. The decline and resurgence of vascular dementia.

    PubMed Central

    Hachinski, V C

    1990-01-01

    Arteriosclerotic narrowing of cerebral arteries was once viewed as the key to mental decline. As Alzheimer's disease gained recognition and the concept of multi-infarct dementia achieved acceptance, vascular dementia came to be regarded as uncommon. The changing nature of cerebral vascular disease, the aging of the population and the widespread use of brain imaging techniques have brought new prominence to vascular dementia, chiefly in the form of an epidemic of "Binswanger's disease". Growing evidence suggests that not only grey matter lesions but also white matter lesions contribute to dementia, that vascular factors commonly coexist and interact with Alzheimer changes and that Alzheimer's disease has a vascular and potentially treatable component. Vascular dementia needs to be redefined, reappraised and reinvestigated. PMID:2403832

  7. MicroRNAs Regulate Vascular Medial Calcification.

    PubMed

    Leopold, Jane A

    2014-01-01

    Vascular calcification is highly prevalent in patients with coronary artery disease and, when present, is associated with major adverse cardiovascular events, including an increased risk of cardiovascular mortality. The pathogenesis of vascular calcification is complex and is now recognized to recapitulate skeletal bone formation. Vascular smooth muscle cells (SMC) play an integral role in this process by undergoing transdifferentiation to osteoblast-like cells, elaborating calcifying matrix vesicles and secreting factors that diminish the activity of osteoclast-like cells with mineral resorbing capacity. Recent advances have identified microRNAs (miRs) as key regulators of this process by directing the complex genetic reprogramming of SMCs and the functional responses of other relevant cell types relevant for vascular calcification. This review will detail SMC and bone biology as it relates to vascular calcification and relate what is known to date regarding the regulatory role of miRs in SMC-mediated vascular calcification.

  8. Contrasting arbuscular mycorrhizal responses of vascular and non-vascular plants to a simulated Palaeozoic CO₂ decline.

    PubMed

    Field, Katie J; Cameron, Duncan D; Leake, Jonathan R; Tille, Stefanie; Bidartondo, Martin I; Beerling, David J

    2012-05-15

    The arbuscular mycorrhizal (AM) fungal symbiosis is widely hypothesized to have promoted the evolution of land plants from rootless gametophytes to rooted sporophytes during the mid-Palaeozoic (480-360 Myr, ago), at a time coincident with a 90% fall in the atmospheric CO(2) concentration ([CO(2)](a)). Here we show using standardized dual isotopic tracers ((14)C and (33)P) that AM symbiosis efficiency (defined as plant P gain per unit of C invested into fungi) of liverwort gametophytes declines, but increases in the sporophytes of vascular plants (ferns and angiosperms), at 440 p.p.m. compared with 1,500 p.p.m. [CO(2)](a). These contrasting responses are associated with larger AM hyphal networks, and structural advances in vascular plant water-conducting systems, promoting P transport that enhances AM efficiency at 440 p.p.m. [CO(2)](a). Our results suggest that non-vascular land plants not only faced intense competition for light, as vascular land floras grew taller in the Palaeozoic, but also markedly reduced efficiency and total capture of P as [CO(2)](a) fell.

  9. [Pharmacological treatment of vascular cognitive impairment].

    PubMed

    Bidzan, Leszek

    2006-01-01

    Vascular dementia is second most common cause of dementia. The paper highlights the most important trends in pharmacological treatment of vascular dementia. Result of a clinical trial of some agents appears to be promising. Pentoxifyline appears to be useful in multi-infarct vascular dementia. Nimodipine produced improvement in subcortical dementia. Some other agents like ginkgo biloba, acetylocholinesterase inhibitors, memantine and other also have shown mild benefit or at least were associated with some stabilization of dementia. PMID:16969897

  10. Cryptic vascular malformations involving the brainstem

    SciTech Connect

    Yeates, A.; Enzmann, D.

    1983-01-01

    Six patients with angiographically cryptic vascular malformations involving the brainstem were examined with computed tomography (CT). The clinical and CT findings of cryptic vascular malformations of the brainstem are described and distinguished from those of brainstem glioma and multiple sclerosis. Calcification within a brainstem lesion that displays relatively little mass effect and shows little contrast enhancement, particularly when associated with a long history of waxing and waning brainstem symptoms, should suggest a vascular malformation.

  11. Direct intratumoral embolization of intranasal vascular tumors.

    PubMed

    Jang, Hyun-Uk; Kim, Tae-Hoon; Park, Chang-Mook; Kim, Jung-Soo

    2013-02-01

    Embolization is a well established technique that facilitates the subsequent surgical removal of vascularized tumors such as juvenile angiofibroma. Preoperative transarterial embolization has proven beneficial for decreasing intraoperative blood loss. However, the procedure is often incomplete owing to extensive vascular structure. Direct intratumoral embolization may help overcome this limitation. We report our experience with embolization of nasal vascular tumors by means of direct intratumoral injection of n-butyl cyanoacrylate (NBCA).

  12. High-flow vascular malformation treatment using ultrasound-guided laser combined with polidocanol sclerotherapy.

    PubMed

    Zhang, Yan; Zhou, Ping; Li, Lan; Li, Jia-le

    2015-07-01

    The current treatment for vascular malformations includes surgery, sclerotherapy, and embolization. However, each method has its limitations, such as recurrence, complications, scarring, and radiation exposure. Therefore, identifying an effective, minimally invasive treatment that reduces lesion recurrence is particularly important. We describe in detail a patient who received treatment with ultrasound-guided laser interruption of feeding vessels combined with polidocanol sclerotherapy after the recurrence of forearm high-flow vascular malformation.

  13. Gestational diabetes, pregnancy hypertension, and late vascular disease.

    PubMed

    Carpenter, Marshall W

    2007-07-01

    -term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an association of insulin resistance with both inflammatory dysregulation and vascular dysfunction. Cohort studies that have used population-based pregnancy databases consistently identify a clinically significant association of both gestational hypertension and preeclampsia with later hypertensive disorders. Associations with coronary artery disease or stroke are less consistent, requiring further investigation. Preventing the evolution of diabetes and lipid and immune dysregulation of the metabolic syndrome has become a silent public health issue because of the epidemic of childhood and early adulthood obesity and the opportunity at hand to treat insulin resistance by behavioral and pharmacological interventions. However, limited available literature highlights the need for long-term cohort studies of women with well-characterized metabolic and vascular profiles during pregnancy and decades later. Our present knowledge suggests that screening for GDM provides an opportunity of pregnancy outcome improvement. Limited studies of diabetes prevention in at-risk patient groups suggest that we may have the opportunity to reduce the risk of later diabetes. Additional investigation is required to determine if interventions that prevent or postpone diabetes also delay the onset of vascular disease.

  14. Supermarket model for vascular disease care.

    PubMed

    Shah, Dhiraj M; Bruni, Karen; Darling, R Clement

    2002-09-01

    A supermarket model for vascular patient care proposes an interdisciplinary group of health care teams such as vascular nurses, interventional radiologists, vascular surgeons, angiologists, internists, cardiologists, and neurologists and facilities such as diagnostic testing laboratories, subcenters such as wound care and foot care centers, atherosclerotic risk prevention centers, rehabilitation centers, vein centers, and socioeconomic follow-up centers that would provide health care of vascular disease in a comprehensive manner in terms of quality care, convenience for patients, 1-stop shopping, education and training, and research and development.

  15. Vascular anomalies: differential diagnosis and mimickers.

    PubMed

    Garzon, Maria C; Weitz, Nicole; Powell, Julie

    2016-03-01

    Vascular anomalies are very common in children and encompass a wide spectrum of diseases. Many vascular anomalies can be mistaken for infantile hemangioma (IH). In addition, there is a variety of rare disorders including benign and malignant tumors that may mimic IH and other types of vascular anomalies. Understanding the clinical features, natural history, and typical clinical course of different types of vascular anomalies is essential in order to make the correct diagnosis and guide management. Radiologic imaging plays an important role in establishing the diagnosis; and when the diagnosis remains in doubt, a biopsy performed by a surgical specialist with expertise may prove to be lifesaving. PMID:27607326

  16. Vascular nursing in Greece: luxury or necessity?

    PubMed

    Georgakarakos, Efstratios; Bitza, Christina; Papanas, Nikolaos; Matsagkas, Miltiadis; Lazarides, Miltos K

    2013-09-01

    Although peripheral arterial disease is prevalent in the primary care setting, insufficient vascular education among nurses and physicians coupled with certain economic constraints undermines treatment efficacy. Moreover, the burden of advanced venous pathology such as posthrombotic syndrome, venous ulcers, and lymphedema remains suboptimally treated. This article advocates the development of a vascular nursing specialty as a means to improving vascular care especially nowadays, when health care providers dictate comprehensive and cost-effective nursing practice and patient management. It also presents the first attempt to organize a Vascular Nursing Educational Session in Greece. PMID:24043676

  17. Scaffolds in vascular regeneration: current status

    PubMed Central

    Thottappillil, Neelima; Nair, Prabha D

    2015-01-01

    An ideal vascular substitute, especially in <6 mm diameter applications, is a major clinical essentiality in blood vessel replacement surgery. Blood vessels are structurally complex and functionally dynamic tissue, with minimal regeneration potential. These have composite extracellular matrix (ECM) and arrangement. The interplay between ECM components and tissue specific cells gives blood vessels their specialized functional attributes. The core of vascular tissue engineering and regeneration relies on the challenges in creating vascular conduits that match native vessels and adequately regenerate in vivo. Out of numerous vascular regeneration concerns, the relevance of ECM emphasizes much attention toward appropriate choice of scaffold material and further scaffold development strategies. The review is intended to be focused on the various approaches of scaffold materials currently in use in vascular regeneration and current state of the art. Scaffold of choice in vascular tissue engineering ranges from natural to synthetic, decellularized, and even scaffold free approach. The applicability of tubular scaffold for in vivo vascular regeneration is under active investigation. A patent conduit with an ample endothelial luminal layer that can regenerate in vivo remains an unanswered query in the field of small diameter vascular tissue engineering. Besides, scaffolds developed for vascular regeneration, should aim at providing functional substitutes for use in a regenerative approach from the laboratory bench to patient bedside. PMID:25632236

  18. Vascular grafting strategies in coronary intervention

    NASA Astrophysics Data System (ADS)

    Knight, Darryl; Gillies, Elizabeth; Mequanint, Kibret

    2014-06-01

    With the growing need for coronary revascularizations globally, several strategies to restore blood flow to the heart have been explored. Bypassing the atherosclerotic coronary arteries with autologous grafts, synthetic prostheses and tissue-engineered vascular grafts continue to be evaluated in search of a readily available vascular graft with clinically acceptable outcomes. The development of such a vascular graft including tissue engineering approaches both in situ and in vitro is herein reviewed, facilitating a detailed comparison on the role of seeded cells in vascular graft patency.

  19. Vascular tumors and malformations in children, Introduction.

    PubMed

    Maguiness, Sheilagh M

    2016-03-01

    Over the past decade, I have been amazed at the growth in the field of vascular anomalies. The recognition of vascular birthmarks as a defined area of medicine is a relatively recent event. The International Society for the Study of Vascular Anomalies (ISSVA) was founded by Drs John Mulliken and Anthony Young in the late 1970s. Mulliken and Glowacki's sentinel 1982 paper on the biologic classification of vascular anomalies further established the field, by providing clarity of nomenclature and unifying concepts that had previously been lacking. PMID:27607317

  20. Tumor vascular disruption using various radiation types

    PubMed Central

    2014-01-01

    The feasibility of disrupting a tumor’s vascular structure with various radiation types and radionuclides is investigated. Calculated absorbed dose profiles for photons and 4He ions suggest that low-energy beta-gamma and alpha emitting radionuclides can deposit sufficient absorbed dose to disrupt a tumor’s vascular structure while minimizing the dose outside the blood vessel. Candidate radionuclides uniformly distributed in microspheres are theoretically investigated with respect to their vascular disruption potential and to offer an alternative to 90Y microsphere therapy. Requisite activities of candidate low-energy beta-gamma and alpha emitting radionuclides to facilitate vascular disruption are calculated. PMID:24749005

  1. Vascular surgery--is it different?

    PubMed

    DeWeese, J A

    1978-12-01

    In 1972 the Society for Vascular Surgery and the North American Chapter of the International Cardiovascular Society recommended that the American Board of Surgery establish a method for the certification of special competence in vascular surgery. The American Board of Surgery in 1974 judged that, for the present, vascular surgery training best could be upgraded by certifying training programs and not individuals. The Residency Review Committee for Surgery now has approved guidelines which define acceptable vascular surgery training programs. These guidelines require approval of the American Medical Association and the governing bodies of the Liaison Committee for Graduate Medical Education before accreditation procedures can be implemented. It is proposed that vascular surgery is different enough from general surgery and cardiothoracic surgery so that special training programs are needed. Vascular surgeons require a fund of knowledge and surgical skills beyond that learned in most surgical programs as well as a special experience with vascular operations if they are to provide optimal patient care. Acceptance of the principle of the accreditation of surgeons caring for vascular surgical problems is an important step in the upgrading of vascular surgery.

  2. GPER inhibits diabetes-mediated RhoA activation to prevent vascular endothelial dysfunction.

    PubMed

    Li, Zilin; Cheng, Liang; Liang, Hongliang; Duan, Weixun; Hu, Jing; Zhi, Weiwei; Yang, Jinbao; Liu, Zhenhua; Zhao, Minggao; Liu, Jincheng

    2016-02-01

    The effect of estrogen receptors on diabetes-induced vascular dysfunction is critical, but ambiguous. Individuals with diabetic vascular disease may require estrogen receptor-specific targeted therapy in the future. The G protein-coupled estrogen receptor (GPER) has beneficial effects on vascular function. However, its fundamental mechanisms are unclear. The RhoA/Rho-kinase pathway contributes to diabetic vascular complications, whereas estrogen can suppress Rho-kinase function. Thus, we assumed that GPER inhibits diabetes-mediated RhoA activation to prevent vascular dysfunction. We further investigated the underlying mechanisms involved in this process. Vascular endothelial cells and ex vivo cultured ovariectomized (OVX) C57BL/6 mouse aortae were treated with high glucose (HG) alone or in combination with GPER agonist (G1). G1 treatment was also administered to OVX db/db mice for 8 weeks. An ex-vivo isovolumic myograph was used to analyze the endothelium-dependent vasodilation and endothelium-independent contraction of mouse aortae. Apoptosis, oxidative stress, and inflammation were attenuated in G1-pretreated vascular endothelial cells. G1 significantly decreased the phosphorylation of inhibitory endothelial nitric oxide (NO) synthase residue threonine 495 (eNOS Thr495), inhibited RhoA expression, and increased NO production. Additionally, G1 rescued the impaired endothelium-dependent relaxation and inhibited RhoA activation in the thoracic aorta of OVX db/db mice and ex-vivo cultured OVX C57BL/6 mouse aortae treated with HG. Estrogens acting via GPER could protect vascular endothelium, and GPER activation might elicit ERα-independent effect to inhibit RhoA/Rho-kinase pathway. Additionally, GPER activation might reduce vascular smooth muscle contraction by inhibiting RhoA activation. Thus, the results of the present study suggest a new therapeutic paradigm for end-stage vascular dysfunction by inhibiting RhoA/Rho-kinase pathway via GPER activation. PMID:26785611

  3. Vascular emergencies in liver trauma.

    PubMed

    Taourel, P; Vernhet, H; Suau, A; Granier, C; Lopez, F M; Aufort, S

    2007-10-01

    The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of complication and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications. PMID:17851012

  4. Computational modeling of vascular anastomoses.

    PubMed

    Migliavacca, Francesco; Dubini, Gabriele

    2005-06-01

    Recent development of computational technology allows a level of knowledge of biomechanical factors in the healthy or pathological cardiovascular system that was unthinkable a few years ago. In particular, computational fluid dynamics (CFD) and computational structural (CS) analyses have been used to evaluate specific quantities, such as fluid and wall stresses and strains, which are very difficult to measure in vivo. Indeed, CFD and CS offer much more variability and resolution than in vitro and in vivo methods, yet computations must be validated by careful comparison with experimental and clinical data. The enormous parallel development of clinical imaging such as magnetic resonance or computed tomography opens a new way toward a detailed patient-specific description of the actual hemodynamics and structural behavior of living tissues. Coupling of CFD/CS and clinical images is becoming a standard evaluation that is expected to become part of the clinical practice in the diagnosis and in the surgical planning in advanced medical centers. This review focuses on computational studies of fluid and structural dynamics of a number of vascular anastomoses: the coronary bypass graft anastomoses, the arterial peripheral anastomoses, the arterio-venous graft anastomoses and the vascular anastomoses performed in the correction of congenital heart diseases. PMID:15772842

  5. Vascular Remodeling in Pulmonary Hypertension

    PubMed Central

    Shimoda, Larissa A; Laurie, Steven S.

    2013-01-01

    Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

  6. Reoperation after vascular ring repair.

    PubMed

    Backer, Carl L; Mongé, Michael C; Russell, Hyde M; Popescu, Andrada R; Rastatter, Jeffrey C; Costello, John M

    2014-01-01

    The majority of patients having surgical intervention for a vascular ring have resolution of their symptoms. However, 5% to 10% of these patients develop recurrent symptoms related either to airway or esophageal compression and may require reoperation. In our series of 300 patients with vascular rings, we performed a reoperation on 26 patients, not all of whom were originally operated on at our institution. The four primary indications for reoperation were Kommerell diverticulum (n = 18), circumflex aorta (n = 2), residual scarring (n = 2), and tracheobronchomalacia requiring aortopexy (n = 4). All patients undergoing reoperation have had preoperative evaluation with bronchoscopy and computed tomographic scanning (CT) with 3-dimensional reconstruction. Patients with dysphagia have had a barium esophagram and esophagoscopy. Patients with a Kommerell diverticulum have undergone resection of the diverticulum and transfer of the left subclavian artery to the left carotid artery. The aortic uncrossing procedure has been used in patients with a circumflex aorta. Aortopexy has been used to treat anterior compression of the trachea by the aorta. Results of these reinterventions have been successful in nearly all cases. Lessons learned from these reoperations can be applied to prevent the need for reoperation by properly selecting the correct initial operation. A dedicated team caring for these children consisting of medical imaging, otolaryngology, cardiovascular-thoracic surgery, and critical care is imperative.

  7. CIRSE Vascular Closure Device Registry

    SciTech Connect

    Reekers, Jim A.; Mueller-Huelsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zelenak, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2011-02-15

    Purpose: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0-14.5] for antegrade access and 1.8% (95% CI 1.1-2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only <0.5% of patients. Postdeployment bleeding occurred in 6.4%, and most these (51.5%) could be managed with light manual compression. During follow-up, other device-related complications were reported in 1.3%: seven false aneurysms, three hematoma >5.9 cm, and two vessel occlusions. Conclusion: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.

  8. Superoxide targets calcineurin signaling in vascular endothelium

    SciTech Connect

    Namgaladze, Dmitry . E-mail: dmitry@zbc.kgu.de; Shcherbyna, Ivanna; Kienhoefer, Joachim; Hofer, H. Werner; Ullrich, Volker

    2005-09-09

    Superoxide emerges as key regulatory molecule in many aspects of vascular physiology and disease, but identification of superoxide targets in the vasculature remains elusive. In this work, we investigated the possibility of inhibition of protein phosphatase calcineurin by superoxide in endothelial cells. We employed a redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) to generate superoxide inside the cells. DMNQ caused inhibition of cellular calcineurin phosphatase activity, which was reversible upon DMNQ removal. Inhibition was suppressed by pre-incubating the cells with copper/zinc superoxide dismutase (Cu,ZnSOD). In addition, reducing cellular Cu,ZnSOD activity by diethylthiocarbamic acid treatment resulted in calcineurin inhibition and enhanced sensitivity to DMNQ. Further, we could show that DMNQ inhibits calcineurin-dependent nuclear translocation and transcriptional activation of NFAT transcription factor, and Cu,ZnSOD or superoxide scavenger Tiron reduced the inhibition. Thus, superoxide generation in endothelial cells results in inhibition of calcineurin signaling, which could have important pathophysiological implications in the vasculature.

  9. Niacin Suppresses Progression of Atherosclerosis by Inhibiting Vascular Inflammation and Apoptosis of Vascular Smooth Muscle Cells.

    PubMed

    Su, Gang; Sun, Guangli; Liu, Hai; Shu, Liliang; Zhang, Jingchao; Guo, Longhui; Huang, Chen; Xu, Jing

    2015-12-29

    BACKGROUND Niacin is a broad-spectrum lipid-regulating drug used for the clinical therapy of atherosclerosis; however, the mechanisms by which niacin ameliorates atherosclerosis are not clear. MATERIAL AND METHODS The effect of niacin on atherosclerosis was assessed by detection of atherosclerotic lesion area. Adhesion molecules in arterial endothelial cells were determined by using qRT-PCR and Western blot analysis. The levels of serum inflammatory cytokines in ApoE-/- mice were detected by using ELISA. We detected the expression levels of phosphorylated nuclear factors-kB (NF-κB) p65 in aortic endothelial cells of mice using Western blot analysis. Furthermore, we investigated the anti-inflammation effect and endothelium-protecting function of niacin and their regulatory mechanisms in vitro. RESULTS Niacin inhibited the progress of atherosclerosis and decreased the levels of serum inflammatory cytokines and adhesion molecules in ApoE-/- mice. Niacin suppressed the activity of NF-κB and apoptosis of vascular smooth muscle cells (VSMCs). Furthermore, niacin induced phosphorylated focal adhesion kinase (FAK) and FAK inhibitor PF-573228 reduced the level of Bcl-2 and elevated the level of cleaved caspase-3 in VSMCs. CONCLUSIONS Niacin inhibits vascular inflammation and apoptosis of VSMCs via inhibiting the NF-κB signaling and the FAK signaling pathway, respectively, thus protecting ApoE-/- mice against atherosclerosis.

  10. Balancing positive and negative plant interactions: how mosses structure vascular plant communities.

    PubMed

    Gornall, Jemma L; Woodin, Sarah J; Jónsdóttir, Ingibjorg S; van der Wal, René

    2011-07-01

    Our understanding of positive and negative plant interactions is primarily based on vascular plants, as is the prediction that facilitative effects dominate in harsh environments. It remains unclear whether this understanding is also applicable to moss-vascular plant interactions, which are likely to be influential in low-temperature environments with extensive moss ground cover such as boreal forest and arctic tundra. In a field experiment in high-arctic tundra, we investigated positive and negative impacts of the moss layer on vascular plants. Ramets of the shrub Salix polaris, herb Bistorta vivipara, grass Alopecurus borealis and rush Luzula confusa were transplanted into plots manipulated to contain bare soil, shallow moss (3 cm) and deep moss (6 cm) and harvested after three growing seasons. The moss layer had both positive and negative impacts upon vascular plant growth, the relative extent of which varied among vascular plant species. Deep moss cover reduced soil temperature and nitrogen availability, and this was reflected in reduced graminoid productivity. Shrub and herb biomass were greatest in shallow moss, where soil moisture also appeared to be highest. The relative importance of the mechanisms by which moss may influence vascular plants, through effects on soil temperature, moisture and nitrogen availability, was investigated in a phytotron growth experiment. Soil temperature, and not nutrient availability, determined Alopecurus growth, whereas Salix only responded to increased temperature if soil nitrogen was also increased. We propose a conceptual model showing the relative importance of positive and negative influences of the moss mat on vascular plants along a gradient of moss depth and illustrate species-specific outcomes. Our findings suggest that, through their strong influence on the soil environment, mat-forming mosses structure the composition of vascular plant communities. Thus, for plant interaction theory to be widely applicable to

  11. Vascular targets for cannabinoids: animal and human studies

    PubMed Central

    Stanley, Christopher; O'Sullivan, Saoirse E

    2014-01-01

    Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1, CBe, TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6 PMID:24329566

  12. Relaxin as a natural agent for vascular health

    PubMed Central

    Bani, Daniele

    2008-01-01

    Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral vascular disease, and renal failure are the main manifestations of cardiovascular disease (CVD), the leading cause of death and disability in developed countries. Continuing insight into the pathophysiology of CVD can allow identification of effective therapeutic strategies to reduce the occurrence of death and/or severe disabilities. In this context, a healthy endothelium is deemed crucial to proper functioning and maintenance of anatomical integrity of the vascular system in many organs. Of note, epidemiologic studies indicate that the incidence of CVD in women is very low until menopause and increases sharply thereafter. The loss of protection against CVD in post-menopausal women has been chiefly attributed to ovarian steroid deficiency. However, besides steroids, the ovary also produces the peptide hormone relaxin (RLX), which provides potent vasoactive effects which render it the most likely candidate as the elusive physiological shield against CVD in fertile women. In particular, RLX has a specific relaxant effect on peripheral and coronary vasculature, exerted by the stimulation of endogenous nitric oxide (NO) generation by cells of the vascular wall, and can induce angiogenesis. Moreover, RLX inhibits the activation of inflammatory leukocytes and platelets, which play a key role in CVD. Experimental studies performed in vascular and blood cell in vitro and in animal models of vascular dysfunction, as well as pioneer clinical observations, have provided evidence that RLX can prevent and/or improve CVD, thus offering background to clinical trials aimed at exploring the broad therapeutic potential of human recombinant RLX as a new cardiovascular drug. PMID:18827902

  13. In Vivo Angiography Quantifies Oxygen-Induced Retinopathy Vascular Recovery

    PubMed Central

    Mezu-Ndubuisi, Olachi J.

    2016-01-01

    ABSTRACT Purpose Retinopathy of prematurity (ROP) is a potentially blinding vasoproliferative disease. There is no standardized way to quantify plus disease (tortuous and dilated retinal vessels) or characterize abnormal recovery during ROP monitoring. This study objectively studies vascular features in live mice during development using noninvasive retinal imaging. Methods Using fluorescein angiography (FA), retinal vascular features were quantified in live mice with oxygen induced retinopathy (OIR). A total of 105 wild-type mice were exposed to 77% oxygen from postnatal day 7 (P7) till P12 (OIR mice). Also, 105 age-matched pups were raised in room air (RA mice). In vivo FA was performed at early (P16 to P20), mid (P23 to P27), late (P30 to P34), and mature (P47) phases of retinal vascular development. Retinal vascular area, retinal vein width, and retinal artery tortuosity were quantified. Results Retinal artery tortuosity was higher in OIR than RA mice at early (p < 0.0001), mid (p < 0.0001), late (p < 0.0001), and mature (p < 0.0001) phases. Retinal vascular area in OIR mice increased from early to mid-phase (p < 0.0001), but remained unchanged from mid to late (p = 0.23), and from late to mature phase (p = 0.98). Retinal vein width was larger in OIR mice compared to RA mice during early phase only. Arteries in OIR mice were more tortuous from early to mid-phase (p < 0.0001), but tortuosity remained stable from mid through mature phase. RA mice had an increase in retinal vascular area from early to late phase, but maintained uniform retinal vein width and retinal artery tortuosity in all phases. Conclusions In vivo FA distinguished arterial and venous features, similar to plus disease, and revealed aberrant recovery of OIR mice (arterial tortuosity, reduced capillary density, and absent neovascular buds) that persisted into adulthood. Retinal artery tortuosity may be a reliable, objective marker of severity of ROP. Infants with abnormal retinal vascular

  14. IP3 receptors regulate vascular smooth muscle contractility and hypertension

    PubMed Central

    Lin, Qingsong; Zhao, Guiling; Fang, Xi; Peng, Xiaohong; Tang, Huayuan; Wang, Hong; Jing, Ran; Liu, Jie; Ouyang, Kunfu

    2016-01-01

    Inositol 1, 4, 5-trisphosphate receptor–mediated (IP3R-mediated) calcium (Ca2+) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle–specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca2+ release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction. We demonstrated that deletion of IP3Rs significantly reduced aortic contractile responses to vasoconstrictors, including phenylephrine, U46619, serotonin, and endothelin 1. Deletion of IP3Rs also dramatically reduced the phosphorylation of MLC20 and MYPT1 induced by U46619. Furthermore, although the basal blood pressure of smTKO mice remained similar to that of wild-type controls, the increase in systolic blood pressure upon chronic infusion of angiotensin II was significantly attenuated in smTKO mice. Taken together, our results demonstrate an important role for IP3R-mediated Ca2+ release in VSMCs in regulating vascular contractility and hypertension. PMID:27777977

  15. Reducing haemodialysis access infection rates.

    PubMed

    Dorman, Amanda; Dainton, Marissa

    Infections are the second most common cause of vascular access loss in the long-term haemodialysis patient, and recent years have seen an increase in healthcare-associated infections (HCAIs) associated with vascular access (Suhail, 2009). There have been a number of drivers including publication guidelines (Department of Health, 2006; 2007) and local protocols providing evidence-based recommendations that, when implemented, can reduce the risk of these infections. In England, the selection of bloodstream infections caused by methicillin resistant staphylococcus aureus (MRSA) as a significant clinical outcome has led to a vast amount of work in this area. Root cause analysis of individual infections (by the clinical teams when these occur) in many specialities identified areas where practice could be improved, including practice relating to vascular access within the renal setting. Manufacturers have also supported this work by focusing on developing products that are designed to reduce the likelihood of infections occurring. One product identified and used within the NHS is Chloraprep. PMID:21646994

  16. Enhanced vascularization of cultured skin substitutes genetically modified to overexpress vascular endothelial growth factor.

    PubMed

    Supp, D M; Supp, A P; Bell, S M; Boyce, S T

    2000-01-01

    Cultured skin substitutes have been used as adjunctive therapies in the treatment of burns and chronic wounds, but they are limited by lack of a vascular plexus. This deficiency leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Genetic modification of cultured skin substitutes to enhance vascularization could hypothetically lead to improved wound healing. To address this hypothesis, human keratinocytes were genetically modified by transduction with a replication incompetent retrovirus to overexpress vascular endothelial growth factor, a specific and potent mitogen for endothelial cells. Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates inoculated with human fibroblasts and either vascular endothelial growth factor-modified or control keratinocytes were prepared, and were cultured in vitro for 21 d. Northern blot analysis demonstrated enhanced expression of vascular endothelial growth factor mRNA in genetically modified keratinocytes and in cultured skin substitutes prepared with modified cells. Furthermore, the vascular endothelial growth factor-modified cultured skin substitutes secreted greatly elevated levels of vascular endothelial growth factor protein throughout the entire culture period. The bioactivity of vascular endothelial growth factor protein secreted by the genetically modified cultured skin substitutes was demonstrated using a microvascular endothelial cell growth assay. Vascular endothelial growth factor-modified and control cultured skin substitutes were grafted to full-thickness wounds on athymic mice, and elevated vascular endothelial growth factor mRNA expression was detected in the modified grafts for at least 2 wk after surgery. Vascular endothelial growth factor-modified grafts exhibited increased numbers of dermal blood vessels and decreased time to vascularization compared with controls. These results indicate that genetic modification of

  17. Hutchinson-Gilford progeria syndrome as a model for vascular aging.

    PubMed

    Brassard, Jonathan A; Fekete, Natalie; Garnier, Alain; Hoesli, Corinne A

    2016-02-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects. Progerin also accumulates in an age-dependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS. The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging. The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age, including increased senescence, altered mechanotransduction and stem cell exhaustion. This article discusses the similarities and differences between age-dependent and HGPS-related vascular aging to highlight the relevance of HGPS as a model for vascular aging. Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular disease.

  18. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor.

    PubMed Central

    Heiss, J D; Papavassiliou, E; Merrill, M J; Nieman, L; Knightly, J J; Walbridge, S; Edwards, N A; Oldfield, E H

    1996-01-01

    Brain tumor-associated cerebral edema arises because tumor capillaries lack normal blood-brain barrier function; vascular permeability factor (VPF, also known as vascular endothelial growth factor, VEGF) is a likely mediator of this phenomenon. Clinically, dexamethasone reduces brain tumor-associated vascular permeability through poorly understood mechanisms. Our goals were to determine if suppression of permeability by dexamethasone might involve inhibition of VPF action or expression, and if dexamethasone effects in this setting are mediated by the glucocorticoid receptor (GR). In two rat models of permeability (peripheral vascular permeability induced by intradermal injection of 9L glioma cell-conditioned medium or purified VPF, and intracerebral vascular permeability induced by implanted 9L glioma), dexamethasone suppressed permeability in a dose-dependent manner. Since 80% of the permeability-inducing activity in 9L-conditioned medium was removed by anti-VPF antibodies, we examined dexamethasone effects of VPF expression in 9L cells. Dexamethasone inhibited FCS- and PDGF-dependent induction of VPF expression. At all levels (intradermal, intracranial, and cell culture), dexamethasone effects were reversed by the GR antagonist mifepristone (RU486). Dexamethasone may decrease brain tumor-associated vascular permeability by two GR-dependent mechanisms: reduction of the response of the vasculature to tumor-derived permeability factors (including VPF), and reduction of VPF expression by tumor cells. PMID:8823305

  19. Vascular tumors of the choroid and retina

    PubMed Central

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-01-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  20. 21 CFR 870.3250 - Vascular clip.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vascular clip. 870.3250 Section 870.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3250 Vascular clip. (a) Identification. A...

  1. 21 CFR 870.3250 - Vascular clip.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Vascular clip. 870.3250 Section 870.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3250 Vascular clip. (a) Identification. A...

  2. A history of vascular and microvascular surgery.

    PubMed

    Rickard, Rory F; Hudson, Donald A

    2014-10-01

    The history of microvascular surgery is intimately linked to that of vascular surgery. Microvascular techniques, developed mainly in China, Japan, Australia, and the United States of America, built on the principles of vascular anastomosis established by pioneers in France, Germany, Italy, and the United States of America. We present a history of the technique here.

  3. Functional preservation of vascular smooth muscle tissue

    NASA Technical Reports Server (NTRS)

    Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.

    1973-01-01

    The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.

  4. Covariance of lichen and vascular plant floras

    USGS Publications Warehouse

    Bennett, J.P.; Wetmore, C.M.

    1999-01-01

    The geographic relationships among taxonomic groups are important to study to determine patterns of biodiversity and whether or not associations occur between large groups, e.g., birds and vascular plants. This study was undertaken to determine relationships between higher plants and lower plants, specifically vascular plant and lichen floras in nine national parks of the Great Lakes region. No significant relationship was found between vascular plant floras and lichen floras in this area, which spans 1200 km longitudinally, or between an additional 19 areas from North America that were less than 1000 km(2) in area. For areas larger than 1000 km(2), however, a significant positive relationship existed for 33 areas that span one to approximately 150 million km(2). The ratio of numbers of vascular plants to lichens appeared to average just over 6 across the 33 areas. In the Great Lakes parks, between 28-30% of either the vascular plant or lichen species were singletons (occurring in only one park), but the parks that contained the most singletons were not congruent: Isle Royale had the most singleton lichens, while Indiana Dunes had the most vascular plant singletons. Fewer lichen species (2%) than vascular plants (4%) occurred in all nine parks. Latitude appeared to explain some of the variation between the two groups: vascular plants decreased with increasing latitude, while lichens increased.

  5. A large vascular leiomyoma of the leg.

    PubMed

    Cigna, E; Maruccia, M; Malzone, G; Malpassini, F; Soda, G; Drudi, F M

    2012-06-01

    A 69-year-old woman with a subcutaneous, large vascular leiomyoma of the leg is presented. The patient had a painful, slow-growing, right medial malleolus mass. Clinical symptoms, US images and histopathologic features are reported. Vascular leiomyoma should be included in the differential diagnosis of painful, lower extremity subcutaneous masses also in lesions of larger dimensions.

  6. Abdominal Distension and Vascular Collapse.

    PubMed

    Cosentino, Gina; Uwaifo, Gabriel I

    2016-04-01

    We present the case of a 43-year-old gentleman who presented to the emergency room with acute abdominal distension, confusion and vascular collapse. The emergent radiologic imaging obtained showed massive bilateral adrenal enlargement, but despite the initial clinical suspicion of possible overwhelming sepsis and/or massive abdominal/intralesional hemorrhage, lab tests based obtained rapidly confirmed the diagnosis of acute Addisonian crisis which responded dramatically to adrenocorticoid hormone replacement therapy and aggressive fluid resuscitation. The patient's established history of metastatic lung cancer confirmed this as a case of metastatic massive bilateral adrenal metastases with an initial presentation of acute adrenal insufficiency which is uncommon in the setting of metastatic carcinomatosis but more typically associated with lymphomas. Recognition of this clinical possibility is vital to enable rapid diagnosis and consequent life saving therapy. PMID:27328473

  7. Redox signaling in vascular angiogenesis.

    PubMed

    Maulik, Nilanjana; Das, Dipak K

    2002-10-15

    Angiogenesis is thought to be regulated by several growth factors (EGF, TGF-alpha, beta-FGF, VEGF). Induction of these angiogenic factors is triggered by various stresses. For instance, tissue hypoxia exerts its pro-angiogenic action through various angiogenic factors, the most notable being vascular endothelial growth factor, which has been mainly associated with initiating the process of angiogenesis through the recruitment and proliferation of endothelial cells. Recently, reactive oxygen species (ROS) have been found to stimulate angiogenic response in the ischemic reperfused hearts. Short exposure to hypoxia/reoxygenation, either directly or indirectly, produces ROS that induce oxidative stress which is associated with angiogenesis or neovascularization. ROS can cause tissue injury in one hand and promote tissue repair in another hand by promoting angiogenesis. It thus appears that after causing injury to the cells, ROS promptly initiate the tissue repair process by triggering angiogenic response.

  8. Vascular permeability—the essentials

    PubMed Central

    2015-01-01

    The vasculature, composed of vessels of different morphology and function, distributes blood to all tissues and maintains physiological tissue homeostasis. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and hyperpermeable vessels with poor blood flow, which further promotes hypoxia and disease propagation. Chronic vessel permeability may also facilitate metastatic spread of cancer. Thus, there is a strong incentive to learn more about an important aspect of vessel biology in health and disease: the regulation of vessel permeability. The current review aims to summarize current insights into different mechanisms of vascular permeability, its regulatory factors, and the consequences for disease. PMID:26220421

  9. [Prefabrication of vascularized facial bones].

    PubMed

    Zimmerer, R; Jehn, P; Spalthoff, S; Kokemüller, H; Gellrich, N-C

    2015-03-01

    Critical size defects in the craniomaxillofacial region often result from ablative tumor surgery, inflammation and posttraumatic deformities. To date, autologous bone grafts are still the gold standard for the reconstruction of these defects; however, they are frequently associated with severe donor site morbidity as well as functional and aesthetic compromises. In this context various resorbable and non-resorbable bone replacement materials have been developed and intensively investigated. Particularly in critical size defects these materials fail due to their lack of osteogenic potential and endogenous vascularization. The combination of alloplastic osteoconductive scaffolds, osteogenic cells, and axial prevascularization in bioartificial bone grafts might present an innovative approach for the microsurgical reconstruction of critical size defects.

  10. Thyroid Hormone and Vascular Remodeling.

    PubMed

    Ichiki, Toshihiro

    2016-01-01

    Both hyperthyroidism and hypothyroidism affect the cardiovascular system. Hypothyroidism is known to be associated with enhanced atherosclerosis and ischemic heart diseases. The accelerated atherosclerosis in the hypothyroid state has been traditionally ascribed to atherogenic lipid profile, diastolic hypertension, and impaired endothelial function. However, recent studies indicate that thyroid hormone has direct anti-atherosclerotic effects, such as production of nitric oxide and suppression of smooth muscle cell proliferation. These data suggest that thyroid hormone inhibits atherogenesis through direct effects on the vasculature as well as modification of risk factors for atherosclerosis. This review summarizes the basic and clinical studies on the role of thyroid hormone in vascular remodeling. The possible application of thyroid hormone mimetics to the therapy of hypercholesterolemia and atherosclerosis is also discussed. PMID:26558400

  11. Hedgehog and Resident Vascular Stem Cell Fate

    PubMed Central

    Mooney, Ciaran J.; Hakimjavadi, Roya; Fitzpatrick, Emma; Kennedy, Eimear; Walls, Dermot; Morrow, David; Redmond, Eileen M.; Cahill, Paul A.

    2015-01-01

    The Hedgehog pathway is a pivotal morphogenic driver during embryonic development and a key regulator of adult stem cell self-renewal. The discovery of resident multipotent vascular stem cells and adventitial progenitors within the vessel wall has transformed our understanding of the origin of medial and neointimal vascular smooth muscle cells (SMCs) during vessel repair in response to injury, lesion formation, and overall disease progression. This review highlights the importance of components of the Hh and Notch signalling pathways within the medial and adventitial regions of adult vessels, their recapitulation following vascular injury and disease progression, and their putative role in the maintenance and differentiation of resident vascular stem cells to vascular lineages from discrete niches within the vessel wall. PMID:26064136

  12. Stem/Progenitor cells in vascular regeneration.

    PubMed

    Zhang, Li; Xu, Qingbo

    2014-06-01

    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

  13. Geometry optimization of branchings in vascular networks

    NASA Astrophysics Data System (ADS)

    Khamassi, Jamel; Bierwisch, Claas; Pelz, Peter

    2016-06-01

    Progress has been made in developing manufacturing technologies which enable the fabrication of artificial vascular networks for tissue cultivation. However, those networks are rudimentary designed with respect to their geometry. This restricts long-term biological functionality of vascular cells which depends on geometry-related fluid mechanical stimuli and the avoidance of vessel occlusion. In the present work, a bioinspired geometry optimization for branchings in artificial vascular networks has been conducted. The analysis could be simplified by exploiting self-similarity properties of the system. Design rules in the form of two geometrical parameters, i.e., the branching angle and the radius ratio of the daughter branches, are derived using the wall shear stress as command variable. The numerical values of these parameters are within the range of experimental observations. Those design rules are not only beneficial for tissue engineering applications. Moreover, they can be used as indicators for diagnoses of vascular diseases or for the layout of vascular grafts.

  14. Smoking cessation strategies in vascular surgery.

    PubMed

    Spangler, Emily L; Goodney, Philip P

    2015-06-01

    Tobacco abuse is a highly prevalent modifiable risk factor in vascular surgery patient populations. Despite the known benefits of smoking cessation, quitting smoking is difficult for most patients. Physician advice to stop smoking can help, though more intensive or multifactorial interventions have greater impact. Smoking cessation initiatives based in vascular clinics are feasible, although currently there is significant variation in physician delivery of smoking cessation interventions. Vascular surgeons are optimally poised to be able to capitalize on the "teachable moment" of the vascular procedure to encourage smoking cessation. Concise and effective smoking cessation strategies include standardized physician "very brief advice" (a standardized advice delivery developed and validated by the National Health Service), referral to telephone counseling, and prescription of pharmacotherapy, all of which are best utilized together. This review will discuss different smoking cessation strategies, as well as their inclusion in multicenter trials designed to study delivery of smoking cessation interventions in vascular surgery patients.

  15. Engineering clinically relevant volumes of vascularized bone.

    PubMed

    Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

    2015-05-01

    Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility.

  16. Engineering clinically relevant volumes of vascularized bone

    PubMed Central

    Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

    2015-01-01

    Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. PMID:25877690

  17. Ceacam1 deletion causes vascular alterations in large vessels.

    PubMed

    Najjar, Sonia M; Ledford, Kelly J; Abdallah, Simon L; Paus, Alexander; Russo, Lucia; Kaw, Meenakshi K; Ramakrishnan, Sadeesh K; Muturi, Harrison T; Raphael, Christian K; Lester, Sumona Ghosh; Heinrich, Garrett; Pierre, Sandrine V; Benndorf, Ralf; Kleff, Veronika; Jaffa, Ayad A; Lévy, Emile; Vazquez, Guillermo; Goldberg, Ira J; Beauchemin, Nicole; Scalia, Rosario; Ergün, Süleyman

    2013-08-15

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance and endothelial survival. However, its role in the morphology of macrovessels remains unknown. Mice lacking Ceacam1 (Cc1-/-) exhibit hyperinsulinemia, which causes insulin resistance and fatty liver. With increasing evidence of an association among hyperinsulinemia, fatty liver disease, and atherosclerosis, we investigated whether Cc1-/- exhibited vascular lesions in atherogenic-prone aortae. Histological analysis revealed impaired endothelial integrity with restricted fat deposition and aortic plaque-like lesions in Cc1-/- aortae, likely owing to their limited lipidemia. Immunohistochemical analysis indicated macrophage deposition, and in vitro studies showed increased leukocyte adhesion to aortic wall, mediated in part by elevation in vascular cell adhesion molecule 1 levels. Basal aortic eNOS protein and NO content were reduced, in parallel with reduced Akt/eNOS and Akt/Foxo1 phosphorylation. Ligand-induced vasorelaxation was compromised in aortic rings. Increased NADPH oxidase activity and plasma 8-isoprostane levels revealed oxidative stress and lipid peroxidation in Cc1-/- aortae. siRNA-mediated CEACAM1 knockdown in bovine aortic endothelial cells adversely affected insulin's stimulation of IRS-1/PI 3-kinase/Akt/eNOS activation by increasing IRS-1 binding to SHP2 phosphatase. This demonstrates that CEACAM1 regulates both endothelial cell autonomous and nonautonomous mechanisms involved in vascular morphology and NO production in aortae. Systemic factors such as hyperinsulinemia could contribute to the pathogenesis of these vascular abnormalities. Cc1-/- mice provide a first in vivo demonstration of distinct CEACAM1-dependent hepatic insulin clearance linking hepatic to macrovascular abnormalities.

  18. Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

    PubMed

    Nyhan, D P; Clougherty, P W; Goll, H M; Murray, P A

    1987-07-01

    Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3114215

  19. 2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

    PubMed

    Ziegler, Kenneth R; Dardik, Alan

    2011-07-01

    The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo.

  20. 2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

    PubMed

    Ziegler, Kenneth R; Dardik, Alan

    2011-07-01

    The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo. PMID:21809965

  1. Histological vascular invasion is a novel prognostic indicator in extranodal natural killer/T-cell lymphoma, nasal type

    PubMed Central

    Wang, Hua; Li, Pengfei; Zhang, Xinke; Xia, Zhongjun; Lu, Yue; Huang, Huiqiang

    2016-01-01

    Extranodal natural killer (NK)/T-cell lymphoma, (ENKTL), nasal type, is an aggressive lymphoma with no validated prognostic parameters, to date. In the present study, vascular invasion by this tumor was retrospectively analyzed in 214 patients with untreated ENKTL to evaluate its association with clinical features, treatment response and prognosis. Histological vascular invasion by the tumor was confirmed in 32.7% of patients with ENKTL. The presence of vascular invasion significantly correlated with poor performance status, B symptoms, extranodal involved sites, advanced stage, elevated serum lactate dehydrogenase, D-dimer and cluster of differentiation 68+ tumor-associated macrophages. Upon treatment termination, the complete remission (CR) rate and overall response rate were significantly lower for the vascular invasion group compared with the non-vascular invasion group. Furthermore, vascular invasion resulted in significantly reduced 5-year progression-free survival (PFS; 21.8 vs. 60.1%) and overall survival (OS; 36.8 vs. 77.0%) rates. Using the multivariate Cox regression model, vascular invasion, stage III/IV and CR after chemotherapy were independent prognostic factors for OS and PFS. Thus, histological vascular invasion by the tumor affected the response to treatment, and was also an independent prognostic factor for OS and PFS in ENKTL, nasal type, suggesting a role for vascular invasion in disease progression. PMID:27446357

  2. [Efficacy of preoperative radiation therapy in hyper-vascular solitary fibrous tumor].

    PubMed

    Okamoto, Noriyoshi; Itokawa, Hiroshi; Moriya, Masao; Fujimoto, Michio; Nagashima, Goro; Suzuki, Ryuta; Fujimoto, Tsukasa

    2009-02-01

    The hyper-vascular form of solitary fibrous tumors (SFTs) is rare and there have been few therapeutic evaluations of this entity. We encountered a hyper-vascular SFT and had difficulty removing it surgically. Following radiotherapy, both tumor size and feeder vessels were reduced and we could proceed with gross total removal. A 29-year-old woman was admitted with a 1-year history of decreasing visual acuity on the right side. Magnetic resonance imaging with gadolinium enhancement showed a homogenous enhancing mass (6x5x5 cm) which expanded the superior and inferior tentorium cerebelli. The tumor was fed by the left posterior cerebral artery, bilateral middle meningeal arteries and the right occipital artery. The first operation employed an occipital transtentorial approach and a highly vascular tumor was found. Tumor resection was limited due to severe bleeding. Histologically, the tumor showed focal hypercellularity with spindle cells and numerous capillaries. Immunohistochemically, the tumor was diffusely positive for CD34 and a diagnosis of SFT, hyper-vascular subtype, was made. After the first operation, local irradiation of a total of 40 Gy was performed. Both the tumor size and vascularity decreased dramatically. At the second operation, gross total removal was able to be performed. Radiotherapy appears effective in reducing the hyper-vascular subtype of SFT and would be one possible therapy to deal with these tumors, given their propensity of excessive bleeding during initial surgery.

  3. Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

    PubMed Central

    Kukongviriyapan, Upa; Pannangpetch, Patchareewan; Kukongviriyapan, Veerapol; Donpunha, Wanida; Sompamit, Kwanjit; Surawattanawan, Praphassorn

    2014-01-01

    Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd. PMID:24662163

  4. Vascular and cognitive functions associated with cardiovascular disease in the elderly

    PubMed Central

    Cohen, Ronald A.; Poppas, Athena; Forman, Daniel E.; Hoth, Karin F.; Haley, Andreana P.; Gunstad, John; Jefferson, Angela L.; Tate, David F.; Paul, Robert H.; Sweet, Lawrence H.; Ono, Mokato; Jerskey, Beth A.; Gerhard-Herman, Marie

    2009-01-01

    This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56–85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease. PMID:18608677

  5. Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.

    PubMed

    Liu, Yu; Yu, Manli; Zhang, Le; Cao, Qingxin; Song, Ying; Liu, Yuxiu; Gong, Jianbin

    2016-08-01

    Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway. PMID:27426491

  6. Bioresorbable vascular scaffolds—time to vanish?

    PubMed Central

    Arroyo, Diego; Cook, Stéphane

    2016-01-01

    The fully bioabsorbable vascular scaffold (BVS) has been developed to reduce late adverse events after coronary stenting such as device thrombosis. The device consists of polylactic acid, which is gradually absorbed within the first few years after its implantation. The initial experience with the device in low-risk patients presenting with simple lesions was satisfying and generated optimism among interventional cardiologists by promising better patient outcomes. However, the unrestricted use of the device in patients presenting with a higher baseline risk and more complex lesions came at the cost of alarmingly high rates of early device thrombosis. The performance of the device largely depends on an optimal implantation technique, which differs from that employed with metallic drug-eluting stents due to the device’s distinct physical propensity. Mid-term outcomes in large-scale randomized clinical trial were disappointing. Although its non-inferiority compared to metallic everolimus-eluting stents was formally met, there was a clear trend towards an increased occurrence of myocardial infarction and device thrombosis during the first year after device implantation. However, the BVS’s putative advantages are expected to manifest themselves at long-term, that is 3 to 5 years after the device has been implanted. Evidence pertaining to these long-term outcomes is eagerly awaited. PMID:27293872

  7. Bioresorbable vascular scaffolds-time to vanish?

    PubMed

    Arroyo, Diego; Cook, Stéphane; Puricel, Serban

    2016-06-01

    The fully bioabsorbable vascular scaffold (BVS) has been developed to reduce late adverse events after coronary stenting such as device thrombosis. The device consists of polylactic acid, which is gradually absorbed within the first few years after its implantation. The initial experience with the device in low-risk patients presenting with simple lesions was satisfying and generated optimism among interventional cardiologists by promising better patient outcomes. However, the unrestricted use of the device in patients presenting with a higher baseline risk and more complex lesions came at the cost of alarmingly high rates of early device thrombosis. The performance of the device largely depends on an optimal implantation technique, which differs from that employed with metallic drug-eluting stents due to the device's distinct physical propensity. Mid-term outcomes in large-scale randomized clinical trial were disappointing. Although its non-inferiority compared to metallic everolimus-eluting stents was formally met, there was a clear trend towards an increased occurrence of myocardial infarction and device thrombosis during the first year after device implantation. However, the BVS's putative advantages are expected to manifest themselves at long-term, that is 3 to 5 years after the device has been implanted. Evidence pertaining to these long-term outcomes is eagerly awaited. PMID:27293872

  8. Acute management of vascular air embolism

    PubMed Central

    Shaikh, Nissar; Ummunisa, Firdous

    2009-01-01

    Vascular air embolism (VAE) is known since early nineteenth century. It is the entrainment of air or gas from operative field or other communications into the venous or arterial vasculature. Exact incidence of VAE is difficult to estimate. High risk surgeries for VAE are sitting position and posterior fossa neurosurgeries, cesarean section, laparoscopic, orthopedic, surgeries invasive procedures, pulmonary overpressure syndrome, and decompression syndrome. Risk factors for VAE are operative site 5 cm above the heart, creation of pressure gradient which will facilitate entry of air into the circulation, orogenital sex during pregnancy, rapid ascent in scuba (self contained underwater breathing apparatus) divers and barotrauma or chest trauma. Large bolus of air can lead to right ventricular air lock and immediate fatality. In up to 35% patient, the foramen ovale is patent which can cause paradoxical arterial air embolism. VAE affects cardiovascular, pulmonary and central nervous system. High index of clinical suspicion is must to diagnose VAE. The transesophgeal echocardiography is the most sensitive device which will detect smallest amount of air in the circulation. Treatment of VAE is to prevent further entrainment of air, reduce the volume of air entrained and haemodynamic support. Mortality of VAE ranges from 48 to 80%. VAE can be prevented significantly by proper positioning during surgery, optimal hydration, avoiding use of nitrous oxide, meticulous care during insertion, removal of central venous catheter, proper guidance, and training of scuba divers. PMID:20009308

  9. [Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia].

    PubMed

    Casas, Meritxell; Calvet, Xavier; Vergara, Mercedes; Bella, Maria Rosa; Junquera, Félix; Martinez-Bauer, Eva; Campo, Rafael

    2015-02-01

    Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended.

  10. Adverse Outcome Pathway for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptors During Development

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  11. Vascular elastic photoacoustic tomography in humans

    NASA Astrophysics Data System (ADS)

    Hai, Pengfei; Zhou, Yong; Liang, Jinyang; Li, Chiye; Wang, Lihong V.

    2016-03-01

    Quantification of vascular elasticity can help detect thrombosis and prevent life-threatening conditions such as acute myocardial infarction or stroke. Here, we propose vascular elastic photoacoustic tomography (VE-PAT) to measure vascular elasticity in humans. VE-PAT was developed by incorporating a linear-array-based photoacoustic computed tomography system with a customized compression stage. By measuring the deformation of blood vessels under uniaxial loading, VE-PAT was able to quantify the vascular compliance. We first demonstrated the feasibility of VE-PAT in blood vessel phantoms. In large vessel phantoms, VE-PAT detected a decrease in vascular compliance due to simulated thrombosis, which was validated by a standard compression test. In small blood vessel phantoms embedded 3 mm deep in gelatin, VE-PAT detected elasticity changes at depths that are difficult to image using other elasticity imaging techniques. We then applied VE-PAT to assess vascular compliance in a human subject and detected a decrease in vascular compliance when an occlusion occurred downstream from the measurement point, demonstrating the potential of VE-PAT in clinical applications such as detection of deep venous thrombosis.

  12. Vascularization in bone tissue engineering constructs

    PubMed Central

    Mercado-Pagán, Ángel E.; Stahl, Alexander M.; Shanjani, Yaser; Yang, Yunzhi

    2016-01-01

    Vascularization of large bone grafts is one of the main challenges of bone tissue engineering (BTE), and has held back the clinical translation of engineered bone constructs for two decades so far. The ultimate goal of vascularized BTE constructs is to provide a bone environment rich in functional vascular networks to achieve efficient osseointegration and accelerate restoration of function after implantation. To attain both structural and vascular integration of the grafts, a large number of biomaterials, cells, and biological cues have been evaluated. This review will present biological considerations for bone function restoration, contemporary approaches for clinical salvage of large bone defects and their limitations, state-of-the-art research on the development of vascularized bone constructs, and perspectives on evaluating and implementing novel BTE grafts in clinical practice. Success will depend on achieving full graft integration at multiple hierarchical levels, both between the individual graft components as well as between the implanted constructs and their surrounding host tissues. The paradigm of vascularized tissue constructs could not only revolutionize the progress of bone tissue engineering, but could also be readily applied to other fields in regenerative medicine for the development of new innovative vascularized tissue designs. PMID:25616591

  13. [A new specialty is born: Vascular medicine].

    PubMed

    Laroche, J-P

    2016-05-01

    On the 4th of December 2015, the French authorities officially recognized the birth of a specialty in vascular medicine entitled CO-DES cardiology-vascular/vascular Medicine. France is the 7th country to obtain this specialty after Switzerland, Germany, Austria, Czech Republic, Slovakia and Slovenia, six countries in the EEC. It has taken years to achieve a long but exciting experience: we went from hopes to disappointments, sometimes with the blues, but lobbying helping… with sustained confidence. This article tells the story of 30 years of struggle to achieve this vascular medicine specialty. Gaston Bachelard wrote: "Nothing is obvious, nothing is given, all is built." For the construction of vascular medicine, we had to overcome many obstacles, nothing was given to us, everything was conquered. Beware "The specialist is one who knows more and more things about an increasingly restricted field, up to 'knowing everything about nothing"' recalled Ralph Barton Ferry, philosopher; so there is room for modesty and humility but also convictions. The physical examination will remain the basis of our exercise. But let us recall the contributions of all those vascular physicians who practiced in the past, together with those currently active, who built day after day, year after year, a vascular medicine of quality. It is because of the trust of our colleagues and our patients that we can occupy the place that is ours today.

  14. Microengineered vascular systems for drug development.

    PubMed

    Hovell, Candice M; Sei, Yoshitaka J; Kim, YongTae

    2015-06-01

    Recent advances in microfabrication technologies and advanced biomaterials have allowed for the development of in vitro platforms that recapitulate more physiologically relevant cellular components and function. Microengineered vascular systems are of particular importance for the efficient assessment of drug candidates to physiological barriers lining microvessels. This review highlights advances in the development of microengineered vascular structures with an emphasis on the potential impact on drug delivery studies. Specifically, this article examines the development of models for the study of drug delivery to the central nervous system and cardiovascular system. We also discuss current challenges and future prospects of the development of microengineered vascular systems. PMID:25424383

  15. BMP SIGNALING IN VASCULAR DEVELOPMENT AND DISEASE

    PubMed Central

    Lowery, Jonathan W.; deCaestecker, Mark P.

    2010-01-01

    Genetic and functional studies indicate that common components of the Bone Morphogenetic Protein (BMP) signaling pathway play critical roles in regulating vascular development in the embryo, and in promoting vascular homeostasis and disease in the adult. However, discrepancies between in vitro and in vivo findings, and distinct functional properties of the BMP signaling pathway in different vascular beds have led to controversies in the field that have been difficult to reconcile. This review attempts to clarify some of these issues by providing an up to date overview of the biology and genetics of BMP signaling relevant to the intact vasculature. PMID:20674464

  16. Oral vascular malformations: laser treatment and management

    NASA Astrophysics Data System (ADS)

    Romeo, U.; Rocchetti, F.; Gaimari, G.; Tenore, G.; Palaia, G.; Lo Giudice, G.

    2016-03-01

    Vascular malformations are a very heterogeneous group of circulatory system's diseases that can involve different kind of vessels: arterial, venous or lymphatic ones. Many treatments, such as conventional surgery, embolization, steroid therapy and laser therapy, are available for vascular lesions. The laser approach relies more therapeutic techniques: the transmucosal thermophotocoagulation, intralesional photocoagulation, the excisional biopsy. Today laser is demonstrated to be the gold standard technique to treat vascular lesions that allows a safe and efficient treatment and a lower post-operative healing time. The only disadvantage is the risk of carbonization that could be avoided by using the multiple-spot single pulsed wave technique.

  17. Maternal uterine vascular remodeling during pregnancy.

    PubMed

    Osol, George; Mandala, Maurizio

    2009-02-01

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

  18. Surgical wound infections after peripheral vascular surgery.

    PubMed

    Turtiainen, J; Hakala, T

    2014-12-01

    Surgical wound infection is one of the most common complications after peripheral vascular surgery. It increases the affected patient's risk for major amputation as well as mortality. Furthermore, surgical wound infection is an additional cost. Wound infections after vascular surgery are of multifactorial nature and generally result from the interplay of patient- and procedure-related factors. The use of systemic antibiotic prophylaxis may be the most important method in preventing surgical wound infections. In this review article, we report the current literature of surgical wound infections after peripheral vascular surgery.

  19. The mechanism of vascular calcification – a systematic review

    PubMed Central

    Karwowski, Wojciech; Naumnik, Beata; Szczepański, Marek; Myśliwiec, Michał

    2012-01-01

    Summary Calcification of vessels reduces their elasticity, affecting hemodynamic parameters of the cardiovascular system. The development of arterial hypertension, cardiac hypertrophy, ischemic heart disease or peripheral arterial disease significantly increases mortality in patients over 60 years of age. Stage of advancement and the extent of accumulation of calcium deposits in vessel walls are key risk factors of ischemic events. Vascular calcification is an active and complex process that involves numerous mechanisms responsible for calcium depositions in arterial walls. They lead to increase in arterial stiffness and in pulse wave velocity, which in turn increases cardiovascular disease morbidity and mortality. In-depth study and thorough understanding of vascular calcification mechanisms may be crucial for establishing an effective vasculoprotective therapy. The aim of this study was to present a comprehensive survey of current state-of-the-art research into the impact of metabolic and hormonal disorders on development of vascular calcification. Due to strong resemblance to the processes occurring in bone tissue, drugs used for osteoporosis treatment (calcitriol, estradiol, bisphosphonates) may interfere with the processes occurring in the vessel wall. On the other hand, drugs used to treat cardiovascular problems (statins, angiotensin convertase inhibitors, warfarin, heparins) may have an effect on bone tissue metabolism. Efforts to optimally control calcium and phosphate concentrations are also beneficial for patients with end-stage renal disease, for whom vessel calcification remains a major problem. PMID:22207127

  20. Preoperative assessment and planning of haemodialysis vascular access.

    PubMed

    Lomonte, Carlo; Basile, Carlo

    2015-06-01

    Effective haemodialysis (HD) requires a reliable vascular access (VA). Clinical practice guidelines strongly recommend the arteriovenous fistula (AVF) as the preferred VA in HD patients. The creation of an AVF should be promoted in all eligible patients who choose HD, as it improves outcomes and reduces costs when compared with central venous catheters. Fistula eligibility is a 'work in progress'. Three steps in order to increase the pool of eligible patients can be individualized: (i) process of care, which includes three fundamental items: the VA team, early VA education and timely VA surgery referral; (ii) preoperative evaluation; (iii) surgical strategy. Nephrologists should be able to play a leading and coordinating role of the VA team. They should design a plan that identifies a sequence of options that can be used to provide adequate renal replacement therapy throughout the life span of every end-stage renal disease patient. The main points of this strategy are (i) early vascular education, in which a 'save the vein program' should always be implemented; (ii) timely VA surgery referral and preoperative evaluation: careful examination of arterial and venous beds is mandatory before VA placement; physical examination in addition to colour Doppler ultrasound mapping improves AVF outcomes; (iii) surgical strategy: a successful VA strategy must take into account vascular anatomy, clinical factors and prognosis.

  1. 3D microtumors in vitro supported by perfused vascular networks.

    PubMed

    Sobrino, Agua; Phan, Duc T T; Datta, Rupsa; Wang, Xiaolin; Hachey, Stephanie J; Romero-López, Mónica; Gratton, Enrico; Lee, Abraham P; George, Steven C; Hughes, Christopher C W

    2016-01-01

    There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This "organs-on-chips" approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This "tumor-on-a-chip" platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID:27549930

  2. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    PubMed Central

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  3. Electrospun Vascular Grafts with Improved Compliance Matching to Native Vessels

    PubMed Central

    Nezarati, Roya M.; Eifert, Michelle B.; Dempsey, David K.; Cosgriff-Hernandez, Elizabeth

    2014-01-01

    Coronary artery bypass grafting (CABG) is one of the most commonly performed major surgeries in the United States. Autologous vessels such as the saphenous vein are the current gold standard for treatment; however, synthetic vascular prostheses made of expanded poly(tetrafluoroethylene) (ePTFE) or poly(ethylene terephthalate) (PET) are used when autologous vessels are unavailable. These synthetic grafts have a high failure rate in small diameter (<4 mm) applications due to rapid re-occlusion via intimal hyperplasia. Current strategies to improve clinical performance are focused on preventing intimal hyperplasia by fabricating grafts with compliance and burst pressure similar to native vessels. To this end, we have developed an electrospun vascular graft from segmented polyurethanes with tunable properties by altering material chemistry and graft microarchitecture. Relationships between polyurethane tensile properties and biomechanical properties were elucidated to select polymers with desirable properties. Graft thickness, fiber tortuosity, and fiber fusions were modulated to provide additional tools for controlling graft properties. Using a combination of these strategies, a vascular graft with compliance and burst pressure exceeding the saphenous vein autograft was fabricated (compliance = 6.0 ± 0.6 %/mmHg × 10−4, burst pressure = 2260 ± 160 mmHg). This graft is hypothesized to reduce intimal hyperplasia associated with low compliance in synthetic grafts and improve long term clinical success. Additionally, the fundamental relationships between electrospun mesh microarchitecture and mechanical properties identified in this work can be utilized in various biomedical applications. PMID:24846218

  4. Prevention of cardiac complications in peripheral vascular surgery

    SciTech Connect

    Cutler, B.S.

    1986-04-01

    The prevalence of severe coronary artery disease in peripheral vascular patients exceeds 50 per cent. Complications of coronary artery disease are the most common causes of mortality following peripheral vascular operations. To reduce the incidence of cardiac complications, it is first necessary to identify patients at risk through screening tests. Screening methods in current use include risk factor analysis, exercise testing, routine coronary angiography, and dipyridamole thallium-201 scintigraphy. The risk factor approach has the advantage of being widely applicable since it makes use of historical, physical, and electrocardiographic findings that are already familiar to surgeons and anesthesiologists. It is also inexpensive. However, it may overlook the patient who has no symptoms of coronary artery disease, possibly as a result of the sedentary lifestyle imposed by complications of peripheral vascular disease. The electrocardiographically monitored stress test will identify the asymptomatic patient with occult coronary disease and is helpful in predicting operative risk. However, a meaningful test is dependent on the patient's ability to exercise--an activity that is frequently limited by claudication, amputation, or arthritis. Exercise testing also suffers from a lack of sensitivity and specificity when compared with coronary arteriography. Routine preoperative coronary angiography overcomes the exercise limitation of treadmill testing but is not widely applicable as a screening test for reasons of cost and inherent risk. Dipyridamole thallium-201 scanning, on the other hand, is safe and of relatively low cost and does not require exercise.

  5. 3D microtumors in vitro supported by perfused vascular networks

    PubMed Central

    Sobrino, Agua; Phan, Duc T. T.; Datta, Rupsa; Wang, Xiaolin; Hachey, Stephanie J.; Romero-López, Mónica; Gratton, Enrico; Lee, Abraham P.; George, Steven C.; Hughes, Christopher C. W.

    2016-01-01

    There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This “organs-on-chips” approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This “tumor-on-a-chip” platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID:27549930

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

    PubMed

    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.

  7. Mechanocompatible Polymer-Extracellular-Matrix Composites for Vascular Tissue Engineering.

    PubMed

    Jiang, Bin; Suen, Rachel; Wang, Jiao-Jing; Zhang, Zheng J; Wertheim, Jason A; Ameer, Guillermo A

    2016-07-01

    Small-diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross-linking, which increases ECM mechanical stiffness compared to native arteries. Herein, the importance of maintaining ECM mechanocompatibility is demonstrated, and a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer is described. Specifically, poly(1,8-octamethylene citrate)-co-cysteine is hybridized to the ECM, forming a polymer-ECM composite that allows for heparin immobilization via maleimide-thiol "click" chemistry. Heparinized composites reduce platelet adhesion by >60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts is 65% lower when compared to ECM-only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2-fold) and increased macrophage infiltration (3.5-fold) compared to ECM-only control grafts. All grafts show similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, a mechanocompatible strategy to improve ECM thromboresistance is described and the importance of ECM mechanical properties for proper in vivo graft performance is highlighted. PMID:27109033

  8. Stromal vascularization prevents corneal ulceration.

    PubMed

    Conn, H; Berman, M; Kenyon, K; Langer, R; Gage, J

    1980-04-01

    Experiments were performed with a model of focal, thermal-induced ulceration to test the clinical impression that vascularization prevents ulceration of the corneal stroma. Slow-release polymers containing a vasoproliferase agent (tumor angiogenesis factor) were placed in corneal pockets 2 mm central to the limbus of albino rabbits. These polymers elicited blood vessel ingrowth up to the implant. Control eyes received empty polymers which caused minimal to no vessel growth. Polymers were removed, and each cornea received a focal, thermal burn placed just central to the polymer site. All control corneas ulcerated: most (79%) developed deep stromal or perforating ulcers. Only 25% of prevascularized corneas developed stromal ulcers, and none was deep or perforating. After thermal burns, vessels in both groups grew at the same linear rate toward the burned area. There was a direct relationship between the distance separating the nearest blood vessel and the burned area at the time of burning and the maximum depth of stromal ulceration. Thus prevention of or less severe stromal ulceration is correlated with the earlier presence of vessels in the burned area.

  9. Fascia and Primo Vascular System.

    PubMed

    Yang, Chun; Du, Yi-Kuan; Wu, Jian-Bin; Wang, Jun; Luan, Ping; Yang, Qin-Lao; Yuan, Lin

    2015-01-01

    The anatomical basis for the concept of acupuncture points/meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the fascia research progress and the relationship among acupuncture points/meridians, primo vascular system (PVS), and fascia. Fascia is as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and holds memory and is highly innervated. Fascia is intimately involved with nourishment of all cells of the body, including those of disease and cancer. The human body's fascia network may be the physical substrate represented by the meridians of TCM. The PVS is a newly found circulatory system; recent increased interest has led to new research and new discoveries in the anatomical and functional aspects of the PVS. The fasciology theory provides new insights into the physiological effects of acupuncture needling on basic cellular mechanisms including connective tissue mechanotransduction and regeneration. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

  10. Surgical management of vascular ring.

    PubMed Central

    Roesler, M; De Leval, M; Chrispin, A; Stark, J

    1983-01-01

    Between 1968 and 1980, 51 children had an operation for various forms of vascular ring. Additional cardiac malformations were present in five patients, and six had noncardiac congenital anomalies. Although symptoms started within the first month of life in 39 infants, only 16 came to operation under three months of age, and a delay of more than six months occurred in 15. Stridor, often life-threatening, and recurrent infections were the most common symptoms, but dysphagia was also important. The reasons for delay in diagnosis are discussed. Barium swallow provided the diagnosis in 44 patients and suggested it in a further four patients. Innominate artery compression of the trachea was not diagnosed by barium swallow. Operations of various types were performed. Accuracy in diagnosis is important because not all patients could be treated through the classic left thoracotomy. Severe tracheomalacia was responsible for the only two deaths in the series; one of these had tracheostomy performed in the referring hospital, the second child also had Fallot's tetralogy. The large majority of the patients have done well, 76% being asymptomatic at follow-up. Minimal to moderate stridor persists among the remainder to the present time. Images Fig. 1a and b. Fig. 2. Fig. 3. Fig. 4. PMID:6824368

  11. Ulinastatin mediates protection against vascular hyperpermeability following hemorrhagic shock

    PubMed Central

    Lin, Bo; Liu, Youtan; Li, Tao; Zeng, Kai; Cai, Shumin; Zeng, Zhenhua; Lin, Caizhu; Chen, Zhongqing; Gao, Youguang

    2015-01-01

    Object: Recent studies have suggested that intrinsic apoptotic signaling cascade is involved in endothelial barrier dysfunction following hemorrhagic shock (HS), which results in vascular hyperpermeability. Our previous study demonstrated that ulinastatin (UTI) inhibits oxidant-induced endothelial hyperpermeability and apoptotic signaling. In present study, we hypothesized that UTI would improve HS-induced vascular hyperpermeability by regulating the intrinsic apoptotic signaling cascade. Methods: Hemorrhagic shock was induced in rats by withdrawing blood to reduce the mean arterial pressure to 40-45 mmHg for 60 min, followed by reperfusion. Mesenteric postcapillary venules were examined for changes in hyperpermeability by intravital microscopy. In vitro, Rat lung microvascular endothelial cells (RLMVECs) were exposed in hemorrhagic shock serum for 120 min, followed by transendothelial electrical resistance (TER) estimation. Mitochondrial release of cytochrome c and caspase-3 activation was estimated in vivo. In vitro, ratio of cell apoptosis was evaluated by Annexin-V/PI double stain assay; mitochondrial membrane potential (∆Ψm) was determined with JC-1; intracellular ATP content was assayed by a commercial kit; reactive oxygen species (ROS) was measured by DCFH-DA; adherens junction protein β-catenin was detected by immunofluorescense staining. Results: In vivo, UTI attenuated HS-induced vascular hyperpermeability versus the HS group (P < 0.05); In vitro, UTI attenuated shock serum induced RLMEC monolayer hyperpermeability (P < 0.05). In vivo, UTI inhibited HS-induced cytochrome c release and caspase-3 activation (P < 0.05). In vitro, shock serum induced cell apoptosis, low ATP level, ∆Ψm depolarization, ROS increase were improved by UTI pre-treatment (P < 0.05). UTI improved shock serum induced disruption of endothelial cell adherens junction. Conclusions: UTI inhibits vascular hyperpermeability following HS. UTI regulates oxidative stress and intrinsic

  12. Tie1 controls angiopoietin function in vascular remodeling and inflammation.

    PubMed

    Korhonen, Emilia A; Lampinen, Anita; Giri, Hemant; Anisimov, Andrey; Kim, Minah; Allen, Breanna; Fang, Shentong; D'Amico, Gabriela; Sipilä, Tuomas J; Lohela, Marja; Strandin, Tomas; Vaheri, Antti; Ylä-Herttuala, Seppo; Koh, Gou Young; McDonald, Donald M; Alitalo, Kari; Saharinen, Pipsa

    2016-09-01

    The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability. PMID:27548530

  13. Reduced placental volume and flow in severe growth restricted fetuses

    PubMed Central

    Abulé, Renata Montes Dourado; Bernardes, Lisandra Stein; Doro, Giovana Farina; Miyadahira, Seizo; Francisco, Rossana Pulcinelli Vieira

    2016-01-01

    OBJECTIVES: To evaluate placental volume and vascular indices in pregnancies with severe fetal growth restriction and determine their correlations to normal reference ranges and Doppler velocimetry results of uterine and umbilical arteries. METHODS: Twenty-seven fetuses with estimated weights below the 3rd percentile for gestational age were evaluated. Placental volume and vascular indices, including vascularization, flow, and vascularization flow indices, were measured by three-dimensional ultrasound using a rotational technique and compared to a previously described nomogram. The observed-to-expected placental volume ratio for gestational age and observed-to-expected placental volume ratio for fetal weight were calculated. Placental parameters correlated with the Doppler velocimetry results of uterine and umbilical arteries. RESULTS: The mean uterine artery pulsatility index was negatively correlated with the observed-to-expected placental volume ratio for gestational age, vascularization index and vascularization flow index. The observed-to-expected placental volume ratio for gestational age and observed-to-expected placental volume ratio for fetal weight and vascularization index were significantly lower in the group with a bilateral protodiastolic notch. No placental parameter correlated with the umbilical artery pulsatility index. CONCLUSIONS: Pregnancies complicated by severe fetal growth restriction are associated with reduced placental volume and vascularization. These findings are related to changes in uterine artery Doppler velocimetry. Future studies on managing severe fetal growth restriction should focus on combined results of placental three-dimensional ultrasound and Doppler studies of uterine arteries. PMID:27438567

  14. Modulation of in vivo tumor radiation response via gold nanoshell-mediated vascular-focused hyperthermia: characterizing an integrated antihypoxic and localized vascular disrupting targeting strategy.

    PubMed

    Diagaradjane, Parmeswaran; Shetty, Anil; Wang, James C; Elliott, Andrew M; Schwartz, Jon; Shentu, Shujun; Park, Hee C; Deorukhkar, Amit; Stafford, R Jason; Cho, Sang H; Tunnell, James W; Hazle, John D; Krishnan, Sunil

    2008-05-01

    We report noninvasive modulation of in vivo tumor radiation response using gold nanoshells. Mild-temperature hyperthermia generated by near-infrared illumination of gold nanoshell-laden tumors, noninvasively quantified by magnetic resonance temperature imaging, causes an early increase in tumor perfusion that reduces the hypoxic fraction of tumors. A subsequent radiation dose induces vascular disruption with extensive tumor necrosis. Gold nanoshells sequestered in the perivascular space mediate these two tumor vasculature-focused effects to improve radiation response of tumors. This novel integrated antihypoxic and localized vascular disrupting therapy can potentially be combined with other conventional antitumor therapies. PMID:18412402

  15. Vascular tumours in infants. Part I: benign vascular tumours other than infantile haemangioma.

    PubMed

    Hoeger, P H; Colmenero, I

    2014-09-01

    Vascular anomalies can be subdivided into vascular tumours and vascular malformations (VMs). While most VMs are present at birth and do not exhibit significant postnatal growth, vascular tumours are characterized by their dynamics of growth and (sometimes) spontaneous regression. This review focuses on benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell haemangioma. While some of them bear clinical resemblance to IH, they can be separated by age of appearance, growth characteristics and/or negative staining for glucose transporter 1. Separation of these tumours from IH is necessary because their outcome and therapeutic options are different. Semimalignant and malignant vascular tumours will be addressed in a separate review.

  16. Dual-Energy Spectral CT: Various Clinical Vascular Applications.

    PubMed

    Machida, Haruhiko; Tanaka, Isao; Fukui, Rika; Shen, Yun; Ishikawa, Takuya; Tate, Etsuko; Ueno, Eiko

    2016-01-01

    Single-source dual-energy (DE) computed tomography (CT) with fast switching of tube voltage allows projection-based image reconstruction, substantial reduction of beam-hardening effects, reconstruction of accurate monochromatic images and material decomposition images (MDIs), and detailing of material composition by using x-ray spectral information. In vascular applications, DE CT is expected to overcome limitations of standard single-energy CT angiography, including patient exposure to nephrotoxic contrast medium and carcinogenic radiation, insufficient contrast vascular enhancement, interference from metallic and beam-hardening artifacts and severe vessel calcification, and limited tissue characterization and perfusion assessment. Acquisition of low-energy monochromatic images and iodine/water MDIs can reasonably reduce contrast agent dose and improve vessel enhancement. Acquisition of virtual noncontrast images, such as water/iodine MDIs, can reduce overall radiation exposure by replacing true noncontrast CT in each examination. Acquisition of monochromatic images by using metal artifact reduction software or acquisition of iodine/water MDIs can reduce metal artifacts with preserved or increased vessel contrast, and subtraction of monochromatic images between two energy levels can subtract coils composed of dense metallic materials. Acquisition of iodine/calcium (ie, hydroxyapatite) MDIs permits subtraction of vessel calcification and improves vessel lumen delineation. Sensitive detection of lipid-rich plaque can be achieved by using fat/water MDIs, the spectral Hounsfield unit curve (energy level vs CT attenuation), and a histogram of effective atomic numbers included in an image. Various MDIs are useful for accurate differentiation among materials with high attenuation values, including contrast medium, calcification, and fresh hematoma. Iodine/water MDIs are used to assess organ perfusion, such as in the lungs and myocardium. Understanding these DE CT

  17. Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

    SciTech Connect

    Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu . E-mail: dxliu001@yahoo.com

    2007-07-13

    Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-{kappa}B activation and nuclear translocation in an I{kappa}B{alpha}-dependent manner. The inhibitory effects were associated with reduction of inhibitor I{kappa}B kinase activity and stabilization of the NF-{kappa}B inhibitor I{kappa}B. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations.

  18. Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension.

    PubMed

    Belo, V A; Guimarães, Danielle A; Castro, Michele Mazzaron

    2015-01-01

    For vascular remodeling in hypertension, it is essential that vascular smooth muscle cells (VSMCs) reshape in order to proliferate and migrate. The extracellular matrix (ECM) needs to be degraded to favor VSMC migration. Many proteases, including matrix metalloproteinases (MMPs), contribute to ECM proteolysis and VSMC migration. Bioactive peptides, hemodynamic forces and reactive oxygen-nitrogen species regulate MMP-2 expression and activity. Increased MMP-2 activity contributes to hypertension-induced maladaptive arterial changes and sustained hypertension. New ECM is synthesized to supply VSMCs with bioactive mediators, which stimulate hypertrophy. MMP-2 stimulates the interaction of VSMCs with newly formed ECM, which triggers intracellular signaling via integrins to induce a phenotypic switch and persistent migration. VSMCs switch from a contractile to a synthetic phenotype in order to migrate and contribute to vascular remodeling in hypertension. MMPs also disrupt growth factors bound to ECM, thus contributing to their capacity to regulate VSMC migration. This review sheds light on the proteolytic effects of MMP-2 on ECM and non-ECM substrates in the vasculature and how these effects contribute to VSMC migration in hypertension. The inhibition of MMP activity as a therapeutic target may make it possible to reduce arterial maladaptation caused by hypertension and prevent the resulting fatal cardiovascular events. PMID:26731549

  19. Hydrogels for Engineering of Perfusable Vascular Networks

    PubMed Central

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

    2015-01-01

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

  20. Lipidomics in vascular health: current perspectives

    PubMed Central

    Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

    2015-01-01

    Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health. PMID:26109865

  1. Hydrogels for Engineering of Perfusable Vascular Networks.

    PubMed

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S P; Machens, Hans-Günther; Schilling, Arndt F

    2015-07-14

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

  2. Reducing Dropouts.

    ERIC Educational Resources Information Center

    Timpane, Michael; And Others

    A group of three conference papers, all addressing the subject of effective programs to decrease the number of school dropouts, is presented in this document. The first paper, "Systemic Approaches to Reducing Dropouts" (Michael Timpane), asserts that dropping out is a symptom of failures in the social, economic, and educational systems. Dropping…

  3. Biomimicry, vascular restenosis and coronary stents.

    PubMed

    Schwartz, R S; van der Giessen, W J; Holmes, D R

    1998-01-01

    Biomimicry is in its earliest stages and is being considered in the realm of tissue engineering. If arterial implants are to limit neointimal thickening, purely passive structures cannot succeed. Bioactivity must be present, either by pharmacologic intervention or by fabricating a 'living stent' that contains active cellular material. As tissue engineering evolves, useful solutions will emerge from applying this knowledge directly to vascular biologic problems resulting from angioplasty, stenting, and vascular prosthesis research.

  4. Radiographic Findings Associated with Vascular Anomalies

    PubMed Central

    Masand, Prakash

    2014-01-01

    Imaging of patients with vascular tumors and malformations has been sufficiently refined to answer pertinent questions when making treatment decisions in this challenging subgroup of pediatric patients. The imaging modalities at hand include conventional radiography, Doppler ultrasound, and magnetic resonance imaging with time-resolved, contrast-material enhanced magnetic resonance angiography. This review article will focus on the characteristic imaging features of some focal and diffuse vascular lesions, which have been classified by their clinical history and physical exam, and further labeled as a vascular tumor or slow-flow versus high-flow vascular malformation based on the updated classification system proposed by the International Society for the Study of Vascular Anomalies. The recent advances in knowledge regarding the biology of these vascular anomalies have led to increased awareness of the current nomenclature. Moreover, with better understanding of the imaging features, the radiologist has become a key player in the multidisciplinary approach offered at various institutions where appropriate treatment algorithms and interventional strategies are put together. This is crucial in avoiding misdiagnosis and improper management. PMID:25045332

  5. Thoracic manifestations of collagen vascular diseases.

    PubMed

    Capobianco, Julia; Grimberg, Alexandre; Thompson, Bruna M; Antunes, Viviane B; Jasinowodolinski, Dany; Meirelles, Gustavo S P

    2012-01-01

    Collagen vascular diseases are a diverse group of immunologically mediated systemic disorders that often lead to thoracic changes. The collagen vascular diseases that most commonly involve the lung are rheumatoid arthritis, progressive systemic sclerosis, systemic lupus erythematosus, polymyositis and dermatomyositis, mixed connective tissue disease, and Sjögren syndrome. Interstitial lung disease and pulmonary arterial hypertension are the main causes of mortality and morbidity among patients with collagen vascular diseases. Given the broad spectrum of possible thoracic manifestations and the varying frequency with which different interstitial lung diseases occur, the interpretation of thoracic images obtained in patients with collagen vascular diseases can be challenging. The task may be more difficult in the presence of treatment-related complications such as drug toxicity and infections, which are common in this group of patients. Although chest radiography is most often used for screening and monitoring of thoracic alterations, high-resolution computed tomography can provide additional information about lung involvement in collagen vascular diseases and may be especially helpful for differentiating specific disease patterns in the lung. General knowledge about the manifestations of thoracic involvement in collagen vascular diseases allows radiologists to provide better guidance for treatment and follow-up of these patients.

  6. The mitochondrial genome of the lycophyte Huperzia squarrosa: the most archaic form in vascular plants.

    PubMed

    Liu, Yang; Wang, Bin; Cui, Peng; Li, Libo; Xue, Jia-Yu; Yu, Jun; Qiu, Yin-Long

    2012-01-01

    Mitochondrial genomes have maintained some bacterial features despite their residence within eukaryotic cells for approximately two billion years. One of these features is the frequent presence of polycistronic operons. In land plants, however, it has been shown that all sequenced vascular plant chondromes lack large polycistronic operons while bryophyte chondromes have many of them. In this study, we provide the completely sequenced mitochondrial genome of a lycophyte, from Huperzia squarrosa, which is a member of the sister group to all other vascular plants. The genome, at a size of 413,530 base pairs, contains 66 genes and 32 group II introns. In addition, it has 69 pseudogene fragments for 24 of the 40 protein- and rRNA-coding genes. It represents the most archaic form of mitochondrial genomes of all vascular plants. In particular, it has one large conserved gene cluster containing up to 10 ribosomal protein genes, which likely represents a polycistronic operon but has been disrupted and greatly reduced in the chondromes of other vascular plants. It also has the least rearranged gene order in comparison to the chondromes of other vascular plants. The genome is ancestral in vascular plants in several other aspects: the gene content resembling those of charophytes and most bryophytes, all introns being cis-spliced, a low level of RNA editing, and lack of foreign DNA of chloroplast or nuclear origin.

  7. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization

    PubMed Central

    Dominguez, Elisa; Raoul, William; Calippe, Bertrand; Sahel, José-Alain; Guillonneau, Xavier; Paques, Michel; Sennlaub, Florian

    2015-01-01

    Aims Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined. Methods and Results We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC) apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC) dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO. Conclusion Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease. PMID:26208283

  8. Azelnidipine inhibits Msx2-dependent osteogenic differentiation and matrix mineralization of vascular smooth muscle cells.

    PubMed

    Shimizu, Takehisa; Tanaka, Toru; Iso, Tatsuya; Kawai-Kowase, Keiko; Kurabayashi, Masahiko

    2012-01-01

    Vascular calcification is an active and regulated process that is similar to bone formation. While calcium channel blockers (CCBs) have been shown to improve outcomes in atherosclerotic vascular disease, it remains unknown whether CCBs have an effect on the process of vascular calcification. Here we investigated whether CCBs inhibit osteogenic differentiation and matrix mineralization of vascular smooth muscle cells induced by Msx2, a key factor of vascular calcification. Human aortic smooth muscle cells (HASMCs) were transduced with adenovirus expressing MSX2 and were treated with 3 distinct CCBs. Azelnidipine, a dihydropyridine subclass of CCBs, significantly decreased alkaline phosphatase (ALP) activity of Msx2-overexpressed HASMCs, whereas verapamil and diltiazem had no effect. Furthermore, azelnidipine, but not verapamil and diltiazem, significantly decreased matrix mineralization of Msx2-overexpressing HASMCs. Azelnidipine significantly attenuated the induction of ALP gene expression by Msx2, a key transcription factor in osteogenesis, while it did not reduce enzymatic activity of ALP. Furthermore, azelnidipine inhibited the ability of Msx2 to activate the ALP gene, but had no effect on Notch-induced Msx2 expression. Given that L-type calcium channels are equally blocked by these CCBs, our results suggest that azelnidipine inhibits the Msx2-dependent process of vascular calcification by mechanisms other than inhibition of calcium channel activity.

  9. Differential effects of relaxin deficiency on vascular aging in arteries of male mice.

    PubMed

    Jelinic, Maria; Tare, Marianne; Conrad, Kirk P; Parry, Laura J

    2015-08-01

    Exogenous treatment with the naturally occurring peptide relaxin increases arterial compliance and reduces vascular stiffness. In contrast, relaxin deficiency reduces the passive compliance of small renal arteries through geometric and compositional vascular remodeling. The role of endogenous relaxin on passive mechanical wall properties in other vascular beds is unknown. Importantly, no studies have investigated the effects of aging in arteries of relaxin-deficient mice. Therefore, we tested the hypothesis that mesenteric and femoral arteries stiffen with aging, and this is exacerbated with relaxin deficiency. Male wild-type (Rln (+/+)) and relaxin knockout (Rln (-/-)) mice were aged to 3, 6, 12, 18, and 23 months. Passive mechanical wall properties were assessed by pressure myography. In both genotypes, there was a significant increase in circumferential stiffening in mesenteric arteries with aging, whereas in the femoral artery, aging reduced volume compliance. This was associated with a reduced ability of the artery to lengthen with aging. The predominant phenotype observed in Rln (-/-) mice was reduced volume compliance in young mice in both mesenteric and femoral arteries. In summary, aging induces circumferential stiffening in mesenteric arteries and axial stiffening in femoral arteries. Passive mechanical wall properties of Rln (-/-) mouse arteries predominantly differ at younger ages compared with Rln (+/+) mice, suggesting that a lack of endogenous relaxin only has a minor effect on vascular aging.

  10. Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis

    PubMed Central

    Kuo, Te-Hui; Tseng, Chien-Tzu; Lin, Wei-Hung; Chao, Jo-Yen; Wang, Wei-Ming; Li, Chung-Yi; Wang, Ming-Cheng

    2015-01-01

    Abstract The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case–control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186–1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure–response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549–2.186) noted in patients with ≥3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE. PMID:26131808

  11. Remodeling and vascular spaces in bone.

    PubMed

    Eriksen, Erik Fink; Eghbali-Fatourechi, Guiti Z; Khosla, Sundeep

    2007-01-01

    In recent years, we have come to appreciate that the close association between bone and vasculature plays a pivotal role in the regulation of bone remodeling and fracture repair. In 2001, Hauge et al. characterized a specialized vascular structure, the bone remodeling compartment (BRC), and showed that the outer lining of this compartment was made up of flattened cells, displaying all the characteristics of lining cells in bone. A decrease in bone turnover leads to a decrease in surfaces covered with remodeling compartments, whereas increased turnover causes an increase. Immunoreactivity for all major osteotropic growth factors and cytokines including osteoprotegerin (OPG) and RANKL has been shown in the cells lining the BRC, which makes the BRC the structure of choice for coupling between resorption and formation. The secretion of these factors inside a confined space separated from the bone marrow would facilitate local regulation of the remodeling process without interference from growth factors secreted by blood cells in the marrow space. The BRC creates an environment where cells inside the structure are exposed to denuded bone, which may enable direct cellular interactions with integrins and other matrix factors known to regulate osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC also constitutes an ideal environment for the seeding of bone metastases, known to have high affinity for bone matrix. Reduction in BRC space brought about by antiresorptive therapies such as bisphosphonates reduce the number of skeletal events in advanced cancer, whereas an increase in BRC space induced by remodeling activators like PTH may increase the bone metastatic burden. The BRC has only been characterized in detail in trabecular bone; there is, however, evidence that a similar structure may exist in cortical bone, but further characterization is needed.

  12. Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia

    PubMed Central

    Hadoke, Patrick W. F.; Takov, Kaloyan; Korczak, Agnieszka; Denvir, Martin A.; Smith, Lee B.

    2016-01-01

    Aims Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall. Methods and Results Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10−10–10-7M; 6 days). Conclusion These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis. PMID:27159530

  13. Mesenteric lymph return is an important contributor to vascular hyporeactivity and calcium desensitization after hemorrhagic shock.

    PubMed

    Zhao, Zi-Gang; Niu, Chun-Yu; Wei, Yan-Ling; Zhang, Yu-Ping; Si, Yong-Hua; Zhang, Jing

    2012-08-01

    Vascular hyporeactivity is an important factor in irreversible shock, whereas calcium desensitization is one of the mechanisms of vascular hyporeactivity, and the intestinal lymphatic pathway plays an important role in multiple organ injury after severe hemorrhagic shock (HS). In this study, our aims were to determine the effects of mesenteric lymph on vascular reactivity during HS and the mechanisms involved. First, the in vivo pressor response was observed by intravenous injection of norepinephrine (3 μg/kg) at different time points after HS. We found that mesenteric lymph duct ligation (MLDL) and mesenteric lymph drainage (MLD) enhanced the pressor response at multiple time points after shock. Next, vascular reactivity and calcium sensitivity in superior mesenteric artery (SMA) vascular rings were examined using an isolated organ perfusion system. Vascular reactivity and calcium sensitivity were higher for SMA rings from rats that had undergone HS plus MLDL or MLD that those from rats that had undergone only HS. The effects of MLDL and MLD on vascular reactivity and calcium sensitivity were significantly increased following incubation with the calcium sensitizer angiotensin II and were reduced after incubation with the calcium sensitivity inhibitor insulin. When SMA rings from normal rats were incubated with mesenteric lymph from rats subjected to HS, lymph obtained 0 to 0.5 h after shock enhanced vascular reactivity and calcium sensitivity, whereas lymph obtained 1 to 3 h after shock blunted these effects. We finally examined vascular reactivity and calcium sensitivity in HS rats subjected to MLD at 0 to 3 h or 1 to 3 h after shock. We found that contractile activity of SMAs in response to norepinephrine or Ca was higher in HS rats subjected to MLD at 1 to 3 h after shock compared with rats subjected to MLD at 0 to 3 h after shock. These results indicate that mesenteric lymph return plays an important role in biphasic changes in vascular reactivity during HS

  14. Sox7, Sox17, and Sox18 Cooperatively Regulate Vascular Development in the Mouse Retina

    PubMed Central

    Zhou, Yulian; Williams, John; Smallwood, Philip M.; Nathans, Jeremy

    2015-01-01

    Vascular development and maintenance are controlled by a complex transcriptional program, which integrates both extracellular and intracellular signals in endothelial cells. Here we study the roles of three closely related SoxF family transcription factors–Sox7, Sox17, and Sox18 –in the developing and mature mouse vasculature using targeted gene deletion on a mixed C57/129/CD1 genetic background. In the retinal vasculature, each SoxF gene exhibits a distinctive pattern of expression in different classes of blood vessels. On a mixed genetic background, vascular endothelial-specific deletion of individual SoxF genes has little or no effect on vascular architecture or differentiation, a result that can be explained by overlapping function and by reciprocal regulation of gene expression between Sox7 and Sox17. By contrast, combined deletion of Sox7, Sox17, and Sox18 at the onset of retinal angiogenesis leads to a dense capillary plexus with a nearly complete loss of radial arteries and veins, whereas the presence of a single Sox17 allele largely restores arterial identity, as determined by vascular smooth muscle cell coverage. In the developing retina, expression of all three SoxF genes is reduced in the absence of Norrin/Frizzled4-mediated canonical Wnt signaling, but SoxF gene expression is unaffected by reduced VEGF signaling in response to deletion of Neuropilin1 (Npn1). In adulthood, Sox7, Sox17, and Sox18 act in a largely redundant manner to maintain blood vessel function, as adult onset vascular endothelial-specific deletion of all three SoxF genes leads to massive edema despite nearly normal vascular architecture. These data reveal critical and partially redundant roles for Sox7, Sox17 and Sox18 in vascular growth, differentiation, and maintenance. PMID:26630461

  15. [Hyperhomocysteinemia as a vascular risk factor in chronic hemodialysis patients].

    PubMed

    Trimarchi, Hernán; Young, Pablo; Díaz, María L; Schropp, Juan; Forrester, Mariano; Freixas, Emilio

    2005-01-01

    Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l. PMID:16433478

  16. Endothelial dysfunction impairs vascular neurotransmission in tail arteries.

    PubMed

    Sousa, Joana B; Fresco, Paula; Diniz, Carmen

    2015-01-01

    The present study intends to clarify if endothelium dysfunction impairs vascular sympathetic neurotransmission. Electrically-evoked tritium overflow (100 pulses/5 Hz) was evaluated in arteries (intact and denuded) or exhibiting some degree of endothelium dysfunction (spontaneously hypertensive arteries), pre-incubated with [(3)H]-noradrenaline in the presence of enzymes (nitric oxide synthase (NOS); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; xanthine oxidase; cyclooxygenase; adenosine kinase) inhibitors and a nucleoside transporter inhibitor. Inhibition of endothelial nitric oxide synthase with L-NIO dihydrochloride reduced tritium overflow in intact arteries whereas inhibition of neuronal nitric oxide synthase with Nω-Propyl-L-arginine hydrochloride was devoid of effect showing that only endothelial nitric oxide synthase is involved in vascular sympathetic neuromodulation. Inhibition of enzymes involved in reactive oxygen species or prostaglandins production with apocynin and allopurinol or indomethacin, respectively, failed to alter tritium overflow. A facilitation or reduction of tritium overflow was observed in the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or of 5-iodotubericidin, respectively, but only in intact arteries. These effects can be ascribed to a tonic inhibitory effect mediated by A1 receptors. In denuded and hypertensive arteries, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH 58261) reduced tritium overflow, suggesting the occurrence of a tonic activation of A2A receptors. When endogenous adenosine bioavailability was increased by the nucleoside transporter inhibitor, S-(4-Nitrobenzyl)-6-thioinosine, tritium overflow increased in intact, denuded and hypertensive arteries. Among the endothelium-derived substances studied that could alter vascular sympathetic transmission only adenosine/adenosine receptor mediated mechanisms were clearly impaired by endothelium injury/dysfunction.

  17. Blood pressure, smoking and alcohol use, association with vascular dementia.

    PubMed

    Peters, Ruth

    2012-11-01

    The success of the ageing global population brings with it a growth in the number of dementia sufferers. Older adults are at highest risk of dementia and are likely to manifest both vascular and Alzheimer's pathology. Blood pressure also changes with ageing and there is evidence linking high blood pressure in midlife to an increased risk of later dementia. Data from later life is sparser. A number of intervention trials have been carried out with antihypertensives and have shown mixed results with regard to cognitive and dementia outcomes (both dementia overall and of vascular and Alzheimer's types). Meta-analyses have in general not found an association between blood pressure lowering and reduced dementia incidence, although the number of cases reported in the placebo controlled trials is invariably lower in the actively treated group. Systematic reviews and meta-analyses have also been published with regard to smoking and alcohol use and incident dementia. Despite mixed reports, overall smoking was associated with an increased risk of later dementia and alcohol with a 'U' or 'J' shaped relationship. Following the systematic reviews subsequent publications tend to report similar findings. The literature in this area suffers from differing populations, lengths of follow up and assessments of both risk factor and outcome. However, at present, maintenance of cognitive function would seem to be best served by treating cardiovascular risk factors in accordance with current guidelines, controlling blood pressure, reducing smoking and if consuming alcohol doing so in moderation. This review will concentrate on the prevention of dementia and attempt to provide an overview of the evidence relating to vascular related dementia and the potential risk factors of hypertension, alcohol use and smoking behaviour.

  18. Endothelial dysfunction impairs vascular neurotransmission in tail arteries.

    PubMed

    Sousa, Joana B; Fresco, Paula; Diniz, Carmen

    2015-01-01

    The present study intends to clarify if endothelium dysfunction impairs vascular sympathetic neurotransmission. Electrically-evoked tritium overflow (100 pulses/5 Hz) was evaluated in arteries (intact and denuded) or exhibiting some degree of endothelium dysfunction (spontaneously hypertensive arteries), pre-incubated with [(3)H]-noradrenaline in the presence of enzymes (nitric oxide synthase (NOS); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; xanthine oxidase; cyclooxygenase; adenosine kinase) inhibitors and a nucleoside transporter inhibitor. Inhibition of endothelial nitric oxide synthase with L-NIO dihydrochloride reduced tritium overflow in intact arteries whereas inhibition of neuronal nitric oxide synthase with Nω-Propyl-L-arginine hydrochloride was devoid of effect showing that only endothelial nitric oxide synthase is involved in vascular sympathetic neuromodulation. Inhibition of enzymes involved in reactive oxygen species or prostaglandins production with apocynin and allopurinol or indomethacin, respectively, failed to alter tritium overflow. A facilitation or reduction of tritium overflow was observed in the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or of 5-iodotubericidin, respectively, but only in intact arteries. These effects can be ascribed to a tonic inhibitory effect mediated by A1 receptors. In denuded and hypertensive arteries, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH 58261) reduced tritium overflow, suggesting the occurrence of a tonic activation of A2A receptors. When endogenous adenosine bioavailability was increased by the nucleoside transporter inhibitor, S-(4-Nitrobenzyl)-6-thioinosine, tritium overflow increased in intact, denuded and hypertensive arteries. Among the endothelium-derived substances studied that could alter vascular sympathetic transmission only adenosine/adenosine receptor mediated mechanisms were clearly impaired by endothelium injury

  19. Progenitor cells in pulmonary vascular remodeling.

    PubMed

    Yeager, Michael E; Frid, Maria G; Stenmark, Kurt R

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow-derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow-derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  20. Restoration of peak vascular conductance after simulated microgravity by maximal exercise

    NASA Technical Reports Server (NTRS)

    Engelke, K. A.; Convertino, V. A.

    1998-01-01

    We sought to determine if (i) peak vascular conductance of the calf was reduced following prolonged exposure to simulated microgravity, and (ii) if maximal cycle ergometry performed at the end of microgravity exposure stimulated a restoration of peak calf vascular conductance. To do this, peak vascular conductance of the calf was recorded following ischaemic plantar flexion exercise to fatigue in seven men after 16 days of head-down tilt (HDT) under two conditions: (i) after one bout of maximal supine cycle ergometry completed 24 h prior to performance of ischaemic plantar flexion exercise, and (ii) in a control (no cycle ergometry) condition. Following HDT, peak vascular conductance was reduced in the control condition (0.38 +/- 0.02 to 0.24 +/- 0.02 ml 100 ml-1 min-1 mmHg-1; P = 0.04), but was restored when subjects performed cycle ergometry (0.33 +/- 0.05 to 0.28 +/- 0.04 ml 100 ml-1 min-1 mmHg-1; P = 0.46). After HDT, time to fatigue during ischaemic plantar flexion exercise was not different from pre-HDT 24 h after performance of exhaustive cycle ergometry (120 +/- 24 vs. 122 +/- 19 s), but was decreased in the control condition (116 +/- 11 vs. 95 +/- 8 s; P = 0.07). These data suggest that a single bout of maximal exercise can provide a stimulus to restore peak vascular conductance and maintain time to fatigue during performance of ischaemic plantar flexion exercise.

  1. The inhibition of calpains ameliorates vascular restenosis through MMP2/TGF-β1 pathway

    PubMed Central

    Tang, Lianghu; Pei, Haifeng; Yang, Yi; Wang, Xiong; Wang, Ting; Gao, Erhe; Li, De; Yang, Yongjian; Yang, Dachun

    2016-01-01

    Restenosis limits the efficacy of vascular percutaneous intervention, in which vascular smooth muscle cell (VSMC) proliferation and activation of inflammation are two primary causal factors. Calpains influence VSMC proliferation and collagen synthesis. However, the roles of calpastatin and calpains in vascular restenosis remain unclear. Here, restenosis was induced by ligating the left carotid artery, and VSMCs were pretreated with platelet-derived growth factor (PDGF)-BB. Adenovirus vector carrying MMP2 sequence and specific small interfering RNA against calpain-1/2 were introduced. Finally, restenosis enhanced the expression of calpain-1/2, but reduced calpastatin content. In calpastatin transgenic mice, lumen narrowing was attenuated gradually and peaked on days 14–21. Cell proliferation and migration as well as collagen synthesis were inhibited in transgenic mice, and expression of calpain-1/2 and MMP2/transforming growth factor-β1 (TGF-β1). Consistently, in VSMCs pretreated with PDGF-BB, calpastatin induction and calpains inhibition suppressed the proliferation and migration of VSMCs and collagen synthesis, and reduced expression of calpain-1/2 and MMP2/TGF-β1. Moreover, simvastatin improved restenosis indicators by suppressing the HIF-1α/calpains/MMP2/TGF-β1 pathway. However, MMP2 supplementation eliminated the vascular protection of calpastatin induction and simvastatin. Collectively, calpains inhibition plays crucial roles in vascular restenosis by preventing neointimal hyperplasia at the early stage via suppression of the MMP2/TGF-β1 pathway. PMID:27453531

  2. Analysis of responses to kallidin, DABK, and DAK in feline hindlimb vascular bed.

    PubMed

    Santiago, J A; Garrison, E A; Champion, H C; Smith, R E; Del Rio, O; Kadowitz, P J

    1995-12-01

    Responses to kallidin, des-Arg9-bradykinin (DABK), and des-Arg10-kallidin (DAK) were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of kallidin, DABK, and DAK into the hindlimb perfusion circuit produced dose-dependent vasodilator responses in the hindlimb vascular bed. Vasodilator responses to kallidin and bradykinin (BK) were similar in magnitude and time course, and both peptides were approximately 100-fold more potent than DABK or DAK. Responses to kallidin were decreased by the kinin B2 antagonist, HOE 140, whereas responses to DABK and DAK were reduced by des-Arg9[Leu8]BK, a kinin B1-receptor antagonist. N omega-nitro-L-arginine methyl ester (L-NAME) reduced vasodilator responses to kallidin, DABK, and DAK, whereas meclofenamate, atropine, and U-37883A, a vascular selective ATP-sensitive K+ (K+ATP) channel-blocking agent, did not alter responses to the three peptides. These data suggest that both kinin B1 and B2 receptors are normally present in the hindlimb vascular bed. These data also suggest that kinin B1 and B2 receptor-mediated vasodilator responses are mediated by the release of nitric oxide and that the activation of K+ATP channels or muscarinic receptors, or the release of vasodilator prostaglandins play little if any role in mediating responses to kallidin, DABK, or DAK in the hindlimb vascular bed of the cat.

  3. Arginase 2 Deficiency Prevents Oxidative Stress and Limits Hyperoxia-Induced Retinal Vascular Degeneration

    PubMed Central

    Suwanpradid, Jutamas; Rojas, Modesto; Behzadian, M. Ali; Caldwell, R. William; Caldwell, Ruth B.

    2014-01-01

    Background Hyperoxia exposure of premature infants causes obliteration of the immature retinal microvessels, leading to a condition of proliferative vitreoretinal neovascularization termed retinopathy of prematurity (ROP). Previous work has demonstrated that the hyperoxia-induced vascular injury is mediated by dysfunction of endothelial nitric oxide synthase resulting in peroxynitrite formation. This study was undertaken to determine the involvement of the ureahydrolase enzyme arginase in this pathology. Methods and Findings Studies were performed using hyperoxia-treated bovine retinal endothelial cells (BRE) and mice with oxygen-induced retinopathy (OIR) as experimental models of ROP. Treatment with the specific arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) prevented hyperoxia-induced apoptosis of BRE cells and reduced vaso-obliteration in the OIR model. Furthermore, deletion of the arginase 2 gene protected against hyperoxia-induced vaso-obliteration, enhanced physiological vascular repair, and reduced retinal neovascularization in the OIR model. Additional deletion of one copy of arginase 1 did not improve the vascular pathology. Analyses of peroxynitrite by quantitation of its biomarker nitrotyrosine, superoxide by dihydroethidium imaging and NO formation by diaminofluoroscein imaging showed that the protective actions of arginase 2 deletion were associated with blockade of superoxide and peroxynitrite formation and normalization of NOS activity. Conclusions Our data demonstrate the involvement of arginase activity and arginase 2 expression in hyperoxia-induced vascular injury. Arginase 2 deletion prevents hyperoxia-induced retinal vascular injury by preventing NOS uncoupling resulting in decreased reactive oxygen species formation and increased nitric oxide bioavailability. PMID:25375125

  4. Established vascular effects of continuous positive airway pressure therapy in patients with obstructive sleep apnoea—an update

    PubMed Central

    Wons, Annette Marie

    2015-01-01

    The aim of this review was to summarize the current data from randomised controlled trials (RCTs) on vascular effects of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA). There is good evidence from RCTs that CPAP lowers blood pressure (BP) to a clinically significant amount. The effect seems to be dependent on the hours of nightly CPAP usage. Data from RCTs have also proven a beneficial effect of CPAP on measures of vascular function such as endothelial function and arterial stiffness. However, there is still a lack of evidence from RCTs proving that CPAP reduces vascular events and mortality. PMID:26101649

  5. Established vascular effects of continuous positive airway pressure therapy in patients with obstructive sleep apnoea-an update.

    PubMed

    Wons, Annette Marie; Kohler, Malcolm

    2015-05-01

    The aim of this review was to summarize the current data from randomised controlled trials (RCTs) on vascular effects of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA). There is good evidence from RCTs that CPAP lowers blood pressure (BP) to a clinically significant amount. The effect seems to be dependent on the hours of nightly CPAP usage. Data from RCTs have also proven a beneficial effect of CPAP on measures of vascular function such as endothelial function and arterial stiffness. However, there is still a lack of evidence from RCTs proving that CPAP reduces vascular events and mortality. PMID:26101649

  6. Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

    SciTech Connect

    Sevostyanova, V. V. Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S.

    2015-10-27

    The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

  7. Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

    NASA Astrophysics Data System (ADS)

    Sevostyanova, V. V.; Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S.

    2015-10-01

    The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

  8. [Retinal vascular diseases reflecting generalized vascular alterations. What can be mutually learnt?].

    PubMed

    Feltgen, N; Franko Zeitz, P

    2014-01-01

    Retinal vascular diseases are mostly caused by systemic vascular diseases. In some cases the systemic disease is already known but in other patients ocular anomalies often provide the first indications of a systemic disease. Treating patients with vascular fundus diseases requires close cooperation between ophthalmologists and specialists in other fields and deciding which routine and specialized diagnostic examinations are necessary in light of the potential risk factors involved requires interdisciplinary communication. This article aims to provide an overview of the most important vascular retinal diseases and which examinations are required to ensure an accurate diagnosis. The retinal vascular diseases with the highest frequency or clinical relevance are hypertensive retinopathy, diabetic retinopathy, retinal vein occlusion and retinal artery occlusion.

  9. Design and development of multilayer vascular graft

    NASA Astrophysics Data System (ADS)

    Madhavan, Krishna

    2011-07-01

    Vascular graft is a widely-used medical device for the treatment of vascular diseases such as atherosclerosis and aneurysm as well as for the use of vascular access and pediatric shunt, which are major causes of mortality and morbidity in this world. Dysfunction of vascular grafts often occurs, particularly for grafts with diameter less than 6mm, and is associated with the design of graft materials. Mechanical strength, compliance, permeability, endothelialization and availability are issues of most concern for vascular graft materials. To address these issues, we have designed a biodegradable, compliant graft made of hybrid multilayer by combining an intimal equivalent, electrospun heparin-impregnated poly-epsilon-caprolactone nanofibers, with a medial equivalent, a crosslinked collagen-chitosan-based gel scaffold. The intimal equivalent is designed to build mechanical strength and stability suitable for in vivo grafting and to prevent thrombosis. The medial equivalent is designed to serve as a scaffold for the activity of the smooth muscle cells important for vascular healing and regeneration. Our results have shown that genipin is a biocompatible crosslinker to enhance the mechanical properties of collagen-chitosan based scaffolds, and the degradation time and the activity of smooth muscle cells in the scaffold can be modulated by the crosslinking degree. For vascular grafting and regeneration in vivo, an important design parameter of the hybrid multilayer is the interface adhesion between the intimal and medial equivalents. With diametrically opposite affinities to water, delamination of the two layers occurs. Physical or chemical modification techniques were thus used to enhance the adhesion. Microscopic examination and graft-relevant functional characterizations have been performed to evaluate these techniques. Results from characterization of microstructure and functional properties, including burst strength, compliance, water permeability and suture

  10. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. We completed an acute pilot study with no placebo...

  11. RGB imaging system for monitoring of skin vascular malformation's laser therapy

    NASA Astrophysics Data System (ADS)

    Jakovels, Dainis; Kuzmina, Ilona; Berzina, Anna; Spigulis, Janis

    2012-06-01

    A prototype RGB imaging system for mapping of skin chromophores consists of a commercial RGB CMOS sensor, RGB LEDs ring-light illuminator and orthogonally orientated polarizers for reducing specular reflectance. The system was used for monitoring of vascular malformations (hemagiomas and telangiectasias) therapy.

  12. Altered baroreflex control of forearm vascular resistance during simulated microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Doerr, D. F.; Vernikos, J.

    1994-01-01

    Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

  13. Diagnosing vascular causes of renal failure.

    PubMed

    Abuelo, J G

    1995-10-15

    The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

  14. Vascular oxidant stress and inflammation in hyperhomocysteinemia.

    PubMed

    Papatheodorou, Louisa; Weiss, Norbert

    2007-11-01

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

  15. Vascular and metabolic reserve in Alzheimer's disease.

    PubMed

    Nagata, K; Kondoh, Y; Atchison, R; Sato, M; Satoh, Y; Watahiki, Y; Hirata, Y; Yokoyama, E

    2000-01-01

    Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

  16. Vascular Protection Following Cerebral Ischemia and Reperfusion

    PubMed Central

    Palomares, Sara Morales; Cipolla, Marilyn J.

    2011-01-01

    Despite considerable research that has contributed to a better understanding of the pathophysiology of stroke, translation of this knowledge into effective therapies has largely failed. The only effective treatment for ischemic stroke is rapid recanalization of an occluded vessel by dissolving the clot with tissue plasminogen activator (tPA). However, stroke adversely affects vascular function as well that can cause secondary brain injury and limit treatment that depends on a patent vasculature. In middle cerebral arteries (MCA), ischemia/reperfusion (I/R) cause loss of myogenic tone, vascular paralysis, and endothelial dysfunction that can lead to loss of autoregulation. In contrast, brain parenchymal arterioles retain considerable tone during I/R that likely contributes to expansion of the infarct into the penumbra. Microvascular dysregulation also occurs during ischemic stroke that causes edema and hemorrhage, exacerbating the primary insult. Ischemic injury of vasculature is progressive with longer duration of I/R. Early postischemic reperfusion has beneficial effects on stroke outcome but can impair vascular function and exacerbate ischemic injury after longer durations of I/R. This review focuses on current knowledge on the effects of I/R on the structure and function of different vascular segments in the brain and highlight some of the more promising targets for vascular protection. PMID:22102980

  17. [Novel mechanism for retinal vascular diseases].

    PubMed

    Suzuma, Kiyoshi

    2015-03-01

    I. A new therapeutic target for diabetic retinopathy. Recent reports state that succinate may be an independent retinal angiogenic factor. We evaluated concentrations in vitreous from proliferative diabetic retinopathy (PDR), and found that succinate increased significantly in PDR. Interestingly, levels of succinate from bevacizumab-pre-injected PDR were normal, suggesting that vascular endothelial growth factor (VEGF) had a positive feedback mechanism for succinate since succinate was previously reported to induce VEGF. II. A new understanding of central retinal vein occlusion (CRVO). We evaluated retinal blood flow velocity with laser speckle flowgraphy (LSFG) made in Japan, and found that cases in which both macular edema and retinal blood flow velocity improved after anti-VEGF therapy had better prognosis. In ischemic CRVO at final visit, mean retinal blood velocity was less than 50% of fellow eyes after 1st anti-VEGF therapy, suggesting that those cases might have poor prognosis. LSFG is useful for evaluation and decision in CRVO treatment. III. From exploration for mechanism in retinal vascular diseases to re-vascularization therapy. The standard treatment for retinal non-perfusion area is scatter laser photocoagulation, which is both invasive of the peripheral retina and may prove destructive. Re-vascularization is an ideal strategy for treatment of retinal non-perfusion area. To develop a new methods for re-vascularization in retinal non-perfusion area, we have designed experiments using a retina without vasculature differentiated from induced pluripotent stem(iPS) cells.

  18. Vascularized tail bone grafts in rats.

    PubMed

    Sempuku, T; Tamai, S; Mizumoto, S; Yajima, H

    1993-03-01

    A new experimental model for vascularized corticocancellous bone grafts was established by investigation of vascular anatomy of the tail in 15 adult Fischer 344 rats and determination of the viability of vascularized tail bone grafts into the abdominal wall in 22 7-week-old rats. The tail bones of 40 rats were then raised on the pedicle of the caudal artery and its venae comitantes, transferred to a resected portion in the femur, and observed for 16 weeks. The vascularized graft showed marked reactive periosteal bone formation during the first and second weeks following transfer, and thereafter, the graft continued to show active bone formation. In transverse section, the sharp processes became rounded. In the cancellous bone, both bone resorption and bone formation were noticeably activated early after transfer, although resorption predominated and the amount of the cancellous bone consequently diminished. The nonvascularized grafts showed "creeping substitution." The results suggest that morphologic adaptation occurs if living (i.e., vascularized) tail bones are transferred to long-bone femurs.

  19. VESGEN Software for Mapping and Quantification of Vascular Regulators

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

    2012-01-01

    VESsel GENeration (VESGEN) Analysis is an automated software that maps and quantifies effects of vascular regulators on vascular morphology by analyzing important vessel parameters. Quantification parameters include vessel diameter, length, branch points, density, and fractal dimension. For vascular trees, measurements are reported as dependent functions of vessel branching generation. VESGEN maps and quantifies vascular morphological events according to fractal-based vascular branching generation. It also relies on careful imaging of branching and networked vascular form. It was developed as a plug-in for ImageJ (National Institutes of Health, USA). VESGEN uses image-processing concepts of 8-neighbor pixel connectivity, skeleton, and distance map to analyze 2D, black-and-white (binary) images of vascular trees, networks, and tree-network composites. VESGEN maps typically 5 to 12 (or more) generations of vascular branching, starting from a single parent vessel. These generations are tracked and measured for critical vascular parameters that include vessel diameter, length, density and number, and tortuosity per branching generation. The effects of vascular therapeutics and regulators on vascular morphology and branching tested in human clinical or laboratory animal experimental studies are quantified by comparing vascular parameters with control groups. VESGEN provides a user interface to both guide and allow control over the users vascular analysis process. An option is provided to select a morphological tissue type of vascular trees, network or tree-network composites, which determines the general collections of algorithms, intermediate images, and output images and measurements that will be produced.

  20. Mitochondria, endothelial cell function, and vascular diseases

    PubMed Central

    Tang, Xiaoqiang; Luo, Yu-Xuan; Chen, Hou-Zao; Liu, De-Pei

    2014-01-01

    Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension, and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction. PMID:24834056

  1. Scalable computer architecture for digital vascular systems

    NASA Astrophysics Data System (ADS)

    Goddard, Iain; Chao, Hui; Skalabrin, Mark

    1998-06-01

    Digital vascular computer systems are used for radiology and fluoroscopy (R/F), angiography, and cardiac applications. In the United States alone, about 26 million procedures of these types are performed annually: about 81% R/F, 11% cardiac, and 8% angiography. Digital vascular systems have a very wide range of performance requirements, especially in terms of data rates. In addition, new features are added over time as they are shown to be clinically efficacious. Application-specific processing modes such as roadmapping, peak opacification, and bolus chasing are particular to some vascular systems. New algorithms continue to be developed and proven, such as Cox and deJager's precise registration methods for masks and live images in digital subtraction angiography. A computer architecture must have high scalability and reconfigurability to meet the needs of this modality. Ideally, the architecture could also serve as the basis for a nonvascular R/F system.

  2. Medical Therapy for Pediatric Vascular Anomalies

    PubMed Central

    Margolin, Judith F.; Soni, Heather Mills; Pimpalwar, Sheena

    2014-01-01

    Vascular anomalies (VAs) comprise a large variety of individual diagnoses that in different phases of treatment require a diverse number of medical specialists to provide optimal care. Medical therapies include agents usually associated with cancer chemotherapy, such as vincristine, as well more immunomodulatory types of drugs, such as glucocorticoids and sirolimus. These immunomodulating drugs are being successfully applied in cases that are typically categorized as vascular tumors, including kaposiform hemangioendothelioma (KHE) and tufted angioma (TA), as well as some of the more invasive types of vascular malformations (i.e., microcystic lymphatic malformations and blue rubber bleb nevus syndrome (BRBNS). These therapies need to be combined with good supportive care, which often involves anticoagulation, antimicrobial prophylaxis, and comprehensive pain and symptom-relief strategies, as well as appropriate drug monitoring and management of side effects of medical treatment. The optimal care of these patients frequently involves close collaboration between surgeons, interventional and conventional radiologists, medical subspecialists, and nurses. PMID:25045333

  3. Mechanisms of vascular calcification and associated diseases.

    PubMed

    Marulanda, Juliana; Alqarni, Saleh; Murshed, Monzur

    2014-01-01

    Mineralization of bone and tooth extracellular matrix (ECM) is a physiologic process, while soft tissue mineralization, also known as ectopic mineralization (calcification), is a pathologic condition. Vascular calcification is common in aging and also in a number of genetic and metabolic disorders. The calcific deposits in arteries complicate the prognosis and increase the morbidity in diseases such as atherosclerosis, diabetes and chronic kidney disease (CKD). To completely understand the pathophysiology of these lifethreatening diseases, it is critical to elucidate the molecular mechanisms underlying vascular calcification. Unveiling these mechanisms will eventually identify new therapeutic targets and also improve the management of the associated complications. In the current review, we discussed the common determinants of ECM mineralization, the mechanism of vascular calcification associated with several human diseases and outlined the most common therapeutic approaches to prevent its progression.

  4. Premature vascular damage in systemic lupus erythematosus.

    PubMed

    Kaplan, Mariana J

    2009-11-01

    Systemic lupus erythematosus (SLE) is a disease associated with a striking increase in the risk of premature cardiovascular (CV) complications due to accelerated atherosclerosis. Traditional CV risk factors seem to be less important predictors of CV events than the presence of active SLE. Immune dysregulation characteristic of lupus appears to play the dominant role in atherogenesis. While both SLE-specific and non-specific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair likely induced by Interferon- could play a prominent role in the induction of accelerated atherosclerosis in SLE. This review summarizes some of the proposed mechanisms that may promote accelerated vascular damage in lupus and explores potential targets for CV risk prevention in this patient population.

  5. Diabetes and its vascular complications in Malaysia.

    PubMed

    Jones, J J; Watkins, P J; Owyong, L Y; Loh, P P; Kutty, M K; Jogie, B

    1978-12-01

    One hundred and thirty-two newly diagnosed Asian diabetic patients (39 Malay, 30 Chinese and 63 Indians) have been studied in Kuala Lumpur. The highest proportion of diabetic patients were Indian and the lowest were Chinese. Vascular complications were equally common in Asian diabetic patients as in Europeans; coronary heart disease was relatively more common in Indians and cerebral vascular disease in Chinese. Twenty percent of all Asian diabetic patients requiring admission to hospital also had coronary heart disease, 9% had cerebral vascular disease and 8% had gangrene or ulceration of the feet. In Kuala Lumpur, diabetes is a very important risk factor for coronary heart disease: 17% of all patients admitted to the General Hospital with coronary heart disease were already diabetic. PMID:749278

  6. Vascular ring diagnosis following respiratory arrest

    PubMed Central

    Robson, Evie Alexandra; Scott, Alison; Chetcuti, Philip; Crabbe, David

    2014-01-01

    Vascular rings can present with non-specific respiratory and/or oesophageal symptoms. Early diagnosis requires a high index of suspicion. This case report describes an uncommon acute presentation of a vascular ring. We report a thriving 14-month-old child with a long history of recurrent wheeze and ‘noisy breathing’. He presented acutely with food bolus impaction in the oesophagus which led to a respiratory arrest. Oesophagoscopy and bronchoscopy suggested vascular ring anomaly. A contrast-enhanced CT scan demonstrated a right-sided aortic arch with left ligamentum arteriosum encircling the oesophagus and airway. The ligament was ligated and divided. At follow-up 6 months later, the infant had mild persistent stridor but was otherwise well. PMID:24895385

  7. Evaluating hospital quality for vascular surgery.

    PubMed

    Gonzalez, Andrew; Osborne, Nicholas

    2015-06-01

    Increasingly, there is a wealth of data available to aid patients in determining where to seek care for quality vascular disease. At times, these data may be difficult for the public to comprehend. Hospital rating organizations, frequently motivated by profit, are marketing directly to consumers with increasingly granular data. In this report, we examine the most popular ratings for hospitals that perform vascular surgical procedures and describe the methodology of each rating system, as well as the validity of the data underscoring these ratings. Understanding how hospital quality is being evaluated and what outcomes measures are being collated allows vascular surgeons to take appropriate actions to ensure the validity of their own hospital ratings. PMID:26655048

  8. Dynamics of nephron-vascular network.

    PubMed

    Postnov, D D; Postnov, D E; Marsh, D J; Holstein-Rathlou, N-H; Sosnovtseva, O V

    2012-12-01

    The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order to learn about processes not directly amenable to experimentation. We demonstrate that: (i) the nearest nephrons are synchronized in-phase due to a vascular propagated electrical coupling, (ii) the next few branching levels display a formation of phase-shifted patterns due to hemodynamic coupling and mode elimination, and (iii) distantly located areas show asynchronous behavior or, if all nephrons and branches are perfectly identical, an infinitely long transient behavior. These results contribute to the understanding of mechanisms responsible for the highly dynamic and limited synchronization observed among groups of nephrons despite of the fairly strong interaction between the individual units.

  9. Regulatory Circuits Controlling Vascular Cell Calcification

    PubMed Central

    Sallam, Tamer; Cheng, Henry; Demer, Linda L.; Tintut, Yin

    2013-01-01

    Vascular calcification is a common feature of chronic kidney disease, cardiovascular disease, and aging. Such abnormal calcium deposition occurs in medial and/or intimal layers of blood vessels as well as in cardiac valves. Once considered a passive and inconsequential finding, the presence of calcium deposits in the vasculature is widely accepted as a predictor of increased morbidity and mortality. Recognition of the importance of vascular calcification in health is driving research into mechanisms that govern its development, progression, and regression. Diverse, but highly interconnected factors, have been implicated, including disturbances in lipid metabolism, oxidative stress, inflammatory cytokines, and mineral and hormonal balances, which can lead to formation of osteoblast-like cells in the artery wall. A tight balance of procalcific and anticalcific regulators dictates the extent of disease. In this review, we focus on the main regulatory circuits modulating vascular cell calcification. PMID:23269436

  10. Neurogenic vascular headaches, food and chemical triggers.

    PubMed

    Trotsky, M B

    1994-04-01

    Recent evidence has demonstrated that neurogenic vascular headaches are a combination of neurological primary events and secondary vasomotor changes. The neurological events involve the hypothalamus and sensory cortex with sympathetic hypofunction and noradrenergic abnormalities. A platelet theory has been proposed but has not really been confirmed as a legitimate cause of the neurogenic vascular headaches. Food and chemicals in foods can act as a precipitating factor in the food-sensitive neurogenic vascular headache patient. In these patients evidence is now being demonstrated to confirm this, but larger patient studies are needed. The food-sensitive migraine patient and cluster headache patient must give a good history and food diary to go along with active challenges and provocative testing in order to determine the causative foods. Any concomitant allergies of inhalants or environmentals must also be treated. The treatment modalities of elimination and rotation diets or provocation neutralization may successfully control the headaches without the need for continuous medications.

  11. Qingxuan Jiangya Decoction Reverses Vascular Remodeling by Inducing Vascular Smooth Muscle Cell Apoptosis in Spontaneously Hypertensive Rats.

    PubMed

    Xiao, Fei; He, Fei; Chen, Hongwei; Lin, Shan; Shen, Aling; Chen, Youqin; Chu, Jianfeng; Peng, Jun

    2016-01-01

    Qingxuan Jiangya Decoction (QXJYD), a traditional Chinese medicine formula prescribed by academician Ke-ji Chen, has been used in China to clinically treat hypertension for decades of years. However, the molecular mechanisms of its action remain largely unknown. In this study, we examined the therapeutic efficacy of QXJYD against elevated systolic blood pressure in the spontaneously hypertensive rat (SHR) model, and investigated the underlying molecular mechanisms. We found that oral administration of QXJYD significantly reduced the elevation of systolic blood pressure in SHR but had no effect on body weight change. Additionally, QXJYD treatment significantly decreased the media thickness and ratio of media thickness/lumen diameter in the carotid arteries of SHR. Moreover, QXJYD remarkably promoted apoptosis of vascular smooth muscle cells and reduced the expression of anti-apoptotic B-cell leukemia/lymphoma 2. Furthermore, QXJYD significantly decreased the plasma Angiotensin II level in SHR. Collectively, our findings suggest that reversing vascular remodeling via inducing VSMC apoptosis could be one of the mechanisms whereby QXJYD treats hypertension. PMID:27455221

  12. Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells.

    PubMed

    Ozasa, Yukako; Akazawa, Hiroshi; Qin, Yingjie; Tateno, Kaoru; Ito, Kaoru; Kudo-Sakamoto, Yoko; Yano, Masamichi; Yabumoto, Chizuru; Naito, Atsuhiko T; Oka, Toru; Lee, Jong-Kook; Minamino, Tohru; Nagai, Toshio; Kobayashi, Yoshio; Komuro, Issei

    2013-10-01

    Notch signaling is involved in an intercellular communication mechanism that is essential for coordinated cell fate determination and tissue morphogenesis. The biological effects of Notch signaling are context-dependent. We investigated the functional and hierarchical relationship between angiotensin (Ang) II receptor signaling and Notch signaling in vascular smooth muscle cells (VSMCs). A fluorogenic substrate assay revealed directly that the enzymatic activity of γ-secretase was enhanced after 10 min of Ang II stimulation in HEK293 cells expressing Ang II type 1 receptor. Notch cleavage by γ-secretase was consistently induced and peaked at 10 min after Ang II stimulation, and the Ang II-stimulated increase in Notch intracellular domain production was significantly suppressed by treatment with the γ-secretase inhibitor DAPT. Treatment with DAPT also significantly reduced the Ang II-stimulated proliferation and migration of human aortic VSMCs, as revealed by BrdU incorporation and the Boyden chamber assay, respectively. Systemic administration of the γ-secretase inhibitor dibenzazepine reduced Ang II-induced medial thickening and perivascular fibrosis in the aortas of wild-type mice. These findings suggest that the hierarchical Ang II receptor-Notch signaling pathway promotes the proliferation and migration of VSMCs, and thereby contributes to the progression of vascular remodeling. PMID:23719127

  13. Changes in endothelial cell proliferation and vascular permeability after systemic lipopolysaccharide administration in the subfornical organ.

    PubMed

    Morita-Takemura, Shoko; Nakahara, Kazuki; Tatsumi, Kouko; Okuda, Hiroaki; Tanaka, Tatsuhide; Isonishi, Ayami; Wanaka, Akio

    2016-09-15

    The subfornical organ (SFO) has highly permeable fenestrated vasculature and is a key site for immune-to-brain communications. Recently, we showed the occurrence of continuous angiogenesis in the SFO. In the present study, we found that systemic administration of bacterial lipopolysaccharide (LPS) reduced the vascular permeability and endothelial cell proliferation. In LPS-administered mice, the SFO vasculature showed a significant decrease in the immunoreactivity of plasmalemma vesicle associated protein-1, a marker of endothelial fenestral diaphragms. These data suggest that vasculature undergoes structural change to decrease vascular permeability in response to systemic LPS administration. PMID:27609286

  14. Update on Pharmacologic Retinal Vascular Toxicity.

    PubMed

    Schwartz, Stephen G; Grzybowski, Andrzej; Wasinska-Borowiec, Weronika; Flynn, Harry W; Mieler, William F

    2015-01-01

    Several medications are associated with retinal vascular toxicity. These include intraocular aminoglycosides, oral contraceptives, interferon alpha, several other agents, and talc, which occurs as a vehicle in some oral medications that may be abused intravenously. As a group, these entities represent a small but clinically relevant category of retinal toxicity from medications. Some of the manifestations (e.g., retinal vascular occlusion) are nonspecific, but others are more specific, including clinically visible talc emboli in retinal vessels. Toxicity may be asymptomatic or may cause irreversible visual loss. By maintaining a high index of suspicion, the correct diagnosis can usually be made.

  15. Pattern formation by vascular mesenchymal cells

    NASA Astrophysics Data System (ADS)

    Garfinkel, Alan; Tintut, Yin; Petrasek, Danny; Boström, Kristina; Demer, Linda L.

    2004-06-01

    In embryogenesis, immature mesenchymal cells aggregate and organize into patterned tissues. Later in life, a pathological recapitulation of this process takes place in atherosclerotic lesions, when vascular mesenchymal cells organize into trabecular bone tissue within the artery wall. Here we show that multipotential adult vascular mesenchymal cells self-organize in vitro into patterns that are predicted by a mathematical model based on molecular morphogens interacting in a reaction-diffusion process. We identify activator and inhibitor morphogens for stripe, spot, and labyrinthine patterns and confirm the model predictions in vitro. Thus, reaction-diffusion principles may play a significant role in morphogenetic processes in adult mesenchymal cells.

  16. Bioactive scaffolds for engineering vascularized cardiac tissues

    PubMed Central

    Chiu, Loraine; Radisic, Milica; Vunjak-Novakovic, Gordana

    2013-01-01

    Functional vascularization is a key requirement for the development and function of most tissues, and most critically cardiac muscle. Rapid and irreversible loss of cardiomyocytes during cardiac infarction directly results from the lack of blood supply. Contractile cardiac grafts, engineered using cardiovascular cells in conjunction with biomaterial scaffolds, are an actively studied method for cardiac repair. In this article, we focus on biomaterial scaffolds designed to mediate the development and maturation of vascular networks, by immobilized growth factors. The interactive effects of multiple vasculogenic factors are discussed in the context of cardiac tissue engineering. PMID:20857391

  17. Vascular Radiology in Trauma: A Review

    SciTech Connect

    Nicholson, Anthony A.

    2004-03-15

    It's been 30 years since an endovascular technique to control traumatic hemorrhage was first described. Despite major technical advances in both diagnostic and therapeutic technology, and a great deal of experience since then, endovascular techniques are rarely considered as part of frontline management for vascular trauma. This review considers the literature and calls for better planning and implementation of diagnostic and image=guided therapeutic facilities. Endovascular techniques should be an essential part of vascular trauma management along with endovascular specialists, partners in trauma teams.

  18. Update on Pharmacologic Retinal Vascular Toxicity.

    PubMed

    Schwartz, Stephen G; Grzybowski, Andrzej; Wasinska-Borowiec, Weronika; Flynn, Harry W; Mieler, William F

    2015-01-01

    Several medications are associated with retinal vascular toxicity. These include intraocular aminoglycosides, oral contraceptives, interferon alpha, several other agents, and talc, which occurs as a vehicle in some oral medications that may be abused intravenously. As a group, these entities represent a small but clinically relevant category of retinal toxicity from medications. Some of the manifestations (e.g., retinal vascular occlusion) are nonspecific, but others are more specific, including clinically visible talc emboli in retinal vessels. Toxicity may be asymptomatic or may cause irreversible visual loss. By maintaining a high index of suspicion, the correct diagnosis can usually be made. PMID:26350526

  19. Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

    PubMed

    Ramakrishnan, Sivasubramanian

    2015-01-01

    Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory.

  20. Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

    PubMed

    Ramakrishnan, Sivasubramanian

    2015-01-01

    Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. PMID:26304581

  1. Critical Role of Striatin in Blood Pressure and Vascular Responses to Dietary Sodium Intake.

    PubMed

    Garza, Amanda E; Pojoga, Luminita H; Moize, Burhanuddin; Hafiz, Wan M; Opsasnick, Lauren A; Siddiqui, Waleed T; Horenstein, Michael; Adler, Gail K; Williams, Gordon H; Khalil, Raouf A

    2015-09-01

    Striatin is a protein regulator of vesicular trafficking in neurons that also binds caveolin-1 and Ca(2+)-calmodulin and could activate endothelial nitric oxide synthase. We have shown that striatin colocalizes with the mineralocorticoid receptor and that mineralocorticoid receptor activation increases striatin levels in vascular cells. To test whether striatin is a regulator of vascular function, wild-type and heterozygous striatin-deficient mice (Strn(+/-)) were randomized in crossover intervention to restricted (0.03%) and liberal sodium (1.6%) diets for 7 days on each diet, and blood pressure and aortic vascular function were measured. Compared with wild-type, sodium restriction significantly reduced blood pressure in Strn(+/-). On liberal salt intake, phenylephrine and high KCl caused a greater vascular contraction in Strn(+/-) than wild-type, and endothelium removal, nitric oxide synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ enhanced phenylephrine contraction to a smaller extent in Strn(+/-) than wild-type. On liberal salt, acetylcholine relaxation was less in Strn(+/-) than in wild-type, and endothelium removal, L-NAME, and ODQ blocked acetylcholine relaxation, suggesting changes in endothelial NO-cGMP. On liberal salt, endothelial nitric oxide synthase mRNA expression and the ratio of endothelial nitric oxide synthase activator pAkt/total Akt were decreased in Strn(+/-) versus wild-type. Vascular relaxation to NO donor sodium nitroprusside was not different among groups. Thus, striatin deficiency is associated with salt sensitivity of blood pressure, enhanced vasoconstriction, and decreased vascular relaxation, suggesting a critical role for striatin, through modulation of endothelial NO-cGMP, in regulation of vascular function and BP during changes in sodium intake.

  2. Factor VIIa binding to endothelial cell protein C receptor protects vascular barrier integrity in vivo

    PubMed Central

    SUNDARAM, J.; KESHAVA, S.; GOPALAKRISHNAN, R.; ESMON, C. T.; PENDURTHI, U. R.; RAO, L . V. M.

    2014-01-01

    Summary Background Recent studies have shown that factor VIIa binds to endothelial cell protein C receptor (EPCR), a cellular receptor for protein C and activated protein C. At present, the physiologic significance of FVIIa interaction with EPCR in vivo remains unclear. Objective: To investigate whether exogenously administered FVIIa, by binding to EPCR, induces a barrier protective effect in vivo. Methods Lipopolysaccharide (LPS)-induced vascular leakage in the lung and kidney, and vascular endothelial growth factor (VEGF)-induced vascular leakage in the skin, were used to evaluate the FVIIa-induced barrier protective effect. Wild-type, EPCR-deficient, EPCR-overexpressing and hemophilia A mice were used in the studies. Results Administration of FVIIa reduced LPS-induced vascular leakage in the lung and kidney; the FVIIa-induced barrier protective effect was attenuated in EPCR-deficient mice. The extent of VEGF-induced vascular leakage in the skin was highly dependent on EPCR expression levels. Therapeutic concentrations of FVIIa attenuated VEGF-induced vascular leakage in control mice but not in EPCR-deficient mice. Blockade of FVIIa binding to EPCR with a blocking mAb completely attenuated the FVIIa-induced barrier protective effect. Similarly, administration of protease-activated receptor 1 antagonist blocked the FVIIa-induced barrier protective effect. Hemophilic mice showed increased vascular permeability, and administration of therapeutic concentrations of FVIIa improved barrier integrity in these mice. Conclusions This is the first study to demonstrate that FVIIa binding to EPCR leads to a barrier protective effect in vivo. This finding may have clinical relevance, as it indicates additional advantages of using FVIIa in treating hemophilic patients. PMID:24977291

  3. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  4. Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation

    PubMed Central

    Nemmar, Abderrahim; Albarwani, Sulayma; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Attoub, Samir; Ali, Badreldin H

    2014-01-01

    Amorphous silica nanoparticles (SiNPs) are being used in biomedical, pharmaceutical, and many other industrial applications entailing human exposure. However, their potential vascular and systemic pathophysiologic effects are not fully understood. Here, we investigated the acute (24 hours) systemic toxicity of intraperitoneally administered 50 nm and 500 nm SiNPs in mice (0.5 mg/kg). Both sizes of SiNPs induced a platelet proaggregatory effect in pial venules and increased plasma concentration of plasminogen activator inhibitor-1. Elevated plasma levels of von Willebrand factor and fibrinogen and a decrease in the number of circulating platelets were only seen following the administration of 50 nm SiNPs. The direct addition of SiNPs to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced with 50 nm SiNPs. Both sizes of SiNPs increased lactate dehydrogenase activity and interleukin 1β concentration. However, tumor necrosis factor α concentration was only increased after the administration of 50 nm SiNPs. Nevertheless, plasma markers of oxidative stress, including 8-isoprostane, thiobarbituric acid reactive substances, catalase, and glutathione S-transferase, were not affected by SiNPs. The in vitro exposure of human umbilical vein endothelial cells to SiNPs showed a reduced cellular viability, and more potency was seen with 50 nm SiNPs. Both sizes of SiNPs caused a decrease in endothelium-dependent relaxation of isolated small mesenteric arteries. We conclude that amorphous SiNPs cause systemic inflammation and coagulation events, and alter vascular reactivity. Overall, the effects observed with 50 nm SiNPs were more pronounced than those with 500 nm SiNPs. These findings provide new insight into the deleterious effect of amorphous SiNPs on vascular homeostasis. PMID:24936130

  5. Vascular restoration: Is there a window of opportunity?

    PubMed

    Sun, Jianhua; Kang, Xiaoran; Li, Tianzhu

    2015-12-01

    The usage of drug eluting stents (DES) has markedly reduced the rates of coronary revascularization procedures compared with bare metal stents (BMS). However, this technology still faces challenges in terms of the prevention of late stent thrombosis, major adverse cardiac events (MACE) progression, and the catch-up phenomenon of restenosis. Restoration of endothelial function upon after stenting, therefore, is the key to mitigating the risk of these toxicities and determining the level of the efficacy and safety of an implant. Review of the clinical studies of multiple DES, has suggested that there exists a window of opportunity, within the first two to three months after stent implantation, for restoring vascular function. If re-endothelialization reaches sufficient level within this period, vascular restoration can occur; however, if this opportunity is missed, re-endothelialization is unlikely to reach the level of endothelial maturation necessary to prevent the late stent thrombosis, MACE progression and the catch-up on restenosis. This hypothesis could aid in explaining variable clinical responses for revascularization treatments such as plain old balloon angioplasty (POBA), BMS, or DES. Patients could be grouped according to responses to the different treatment modalities: for Type 1 patients, POBA is sufficient and safe because they possess the capacity with effective endothelial response; for Type 2 patients, re-endothelialization occurs within the window but BMS are needed to maintain the arterial lumen open; for Type 3 individuals, overly accelerated vascular smooth muscle proliferation render sufficient re-endothelialization impossible. Designing based on this principle predicts that the next technology advancement for the interventional cardiology will not be biodegradable DES by default, but rather a DES that can spur early restoration of the endothelial function within the window period.

  6. Caveolin-3 Promotes a Vascular Smooth Muscle Contractile Phenotype

    PubMed Central

    Gutierrez-Pajares, Jorge L.; Iturrieta, Jeannette; Dulam, Vipin; Wang, Yu; Pavlides, Stephanos; Malacari, Gabriella; Lisanti, Michael P.; Frank, Philippe G.

    2015-01-01

    Epidemiological studies have demonstrated the importance of cardiovascular diseases in Western countries. Among the cell types associated with a dysfunctional vasculature, smooth muscle (SM) cells are believed to play an essential role in the development of these illnesses. Vascular SM cells are key regulators of the vascular tone and also have an important function in the development of atherosclerosis and restenosis. While in the normal vasculature, contractile SM cells are predominant, in atherosclerotic vascular lesions, synthetic cells migrate toward the neointima, proliferate, and synthetize extracellular matrix proteins. In the present study, we have examined the role of caveolin-3 in the regulation of SM cell phenotype. Caveolin-3 is expressed in vivo in normal arterial SM cells, but its expression appears to be lost in cultured SM cells. Our data show that caveolin-3 expression in the A7r5 SM cell line is associated with increased expression of contractility markers such as SM α-actin, SM myosin heavy chain but decreased expression of the synthetic phenotype markers such as p-Elk and Klf4. Moreover, we also show that caveolin-3 expression can reduce proliferation upon treatment with LDL or PDGF. Finally, we show that caveolin-3-expressing SM cells are less sensitive to apoptosis than control cells upon treatment with oxidized LDL. Taken together, our data suggest that caveolin-3 can regulate the phenotypic switch between contractile and synthetic SM cells. A better understanding of the factors regulating caveolin-3 expression and function in this cell type will permit the development of a better comprehension of the factors regulating SM function in atherosclerosis and restenosis. PMID:26664898

  7. Pentoxifylline for vascular health: a brief review of the literature.

    PubMed

    McCarty, Mark F; O'Keefe, James H; DiNicolantonio, James J

    2016-01-01

    Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes-some of them attributable to pentoxifylline metabolites-appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable. PMID:26870389

  8. Pentoxifylline for vascular health: a brief review of the literature

    PubMed Central

    McCarty, Mark F; O'Keefe, James H; DiNicolantonio, James J

    2016-01-01

    Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes—some of them attributable to pentoxifylline metabolites—appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable. PMID:26870389