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Sample records for compound improving endothelial

  1. Resveratrol: A Multifunctional Compound Improving Endothelial Function

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    Li, Huige; F?rstermann, Ulrich

    2009-01-01

    The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

  2. Endothelial keratoplasty: improvement of vision after healthy donor tissue exchange.

    Science.gov (United States)

    Chen, Edwin S; Shamie, Neda; Terry, Mark A; Hoar, Karen L

    2008-04-01

    To report 3 cases of graft exchange by using a microkeratome-prepared donor tissue in place of a manually prepared donor tissue for inadequate postoperative visual acuity after deep lamellar endothelial keratoplasty and to discuss possible etiologies. Prospective, observational case series. The patients were 3 consecutive patients who underwent endothelial graft replacement for unsatisfactory vision after initial deep lamellar endothelial keratoplasty. This is a review of clinical findings in 3 cases of endothelial keratoplasty that underwent graft exchange for unacceptable vision after deep lamellar endothelial keratoplasty. Two patients benefited from graft exchange by using a microkeratome-prepared donor in place of a manually prepared donor with improvement in best spectacle-corrected visual acuity and 1 did not because of recipient bed irregularities. Vision improved in this patient with penetrating keratoplasty. Endothelial keratoplasty results in rapid visual recovery and excellent vision. However, fewer eyes achieve 20/20 vision than with full-thickness penetrating keratoplasty. This report shows that some patients with suboptimal vision after endothelial keratoplasty felt to be caused by interface optical problems may benefit from either graft exchange or penetrating keratoplasty.

  3. Antiplatelet aggregation and endothelial protection of I4, a new synthetic anti-diabetes sulfonylurea compound.

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    Ma, Lingman; Lu, Na; Wu, Guanzhong

    2015-01-01

    I4 is a new synthetic anti-diabetes sulfonylurea compound. The aim of present study was to investigate the preventive effects and primary action mechanisms of I4 on platelet-mediated arterial thrombosis. Platelet aggregation and 5-hydroxytryptamine (5-HT) secretion ex vivo was detected. The time-to-occlusion (TTO), thrombus weight and content of von Willebrand factor (vWF) in rat model of electrical- and ferric chloride-induced vessel occlusion were determined. Meanwhile, a rat model of type 2 diabetes mellitus (T2DM) was established to evaluate the effect of I4 on levels of plasma p-selectin, 6-keto-prostaglandin F1a (6-keto-PGF1a), thromboxane B2 (TXB2), tissue-type plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1). NO synthesis, NOS activity, adhesion of platelet toward endothelial cell and intercellular adhesion molecule-1 (ICAM-1) expression were examined. Results showed that I4 exhibited a higher inhibitory potency than Glimepiride on ADP-induced platelet aggregation and 5-HT release ex vivo. In addition, I4 reduced the thrombus weight and content of vWF and markedly prolonged TTO. Oral administration of I4 (1 ∼ 10 mg/kg) inhibited p-selectin production, elevated the ratio of plasma 6-keto-PGF1a/TXB2 and t-PA/PAI-1 in T2DM rats. Furthermore, I4 significantly improved NO synthesis and NOS activity, lowered adhesion ratio of platelet toward endothelial cells and ICAM-1 expression on HUVECs. These observations suggest that I4 markedly improves platelet-mediated arterial thrombosis by inhibiting platelet activation and release reaction, ameliorating the endothelial dysfunction such as the suppression of vWF production and the reduction of the overexpression of ICAM-1, displayed its potential in alleviating diabetes-associated vascular complications.

  4. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions.

    Science.gov (United States)

    Ghosh, Suparna; Lakshmanan, Arun P; Hwang, Mu Ji; Kubba, Haidar; Mushannen, Ahmed; Triggle, Chris R; Ding, Hong

    2015-12-01

    The cellular mechanisms whereby metformin, the first line drug for type 2 diabetes (T2DM), mediates its antidiabetic effects remain elusive, particularly as to whether metformin has a direct protective action on the vasculature. This study was designed to determine if a brief 3-h exposure to metformin protects endothelial function against the effects of hyperglycaemia. We investigated the protective effects of metformin on endothelial-dependent vasodilatation (EDV) in thoracic aortae from T2DM db/db mice and on high glucose (HG, 40 mM) induced changes in endothelial nitric oxide synthase (eNOS) signaling in mouse microvascular endothelial cells (MMECs) in culture. Exposure of aortae from db+/? non-diabetic control mice to high glucose (HG, 40 mM) containing Krebs for 3-h significantly (Pmetformin; metformin also improved ACh-induced EDV in aortae from diabetic db/db mice. Immunoblot analysis of MMECs cultured in HG versus NG revealed a significant reduction of the ratio of phosphorylated (p-eNOS)/eNOS and p-Akt/Akt, but not the expression of total eNOS or Akt. The 3-h exposure of MMECs to metformin significantly (Pmetformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. NON-PHARMACOLOGICAL CONCEPTS OF ENDOTHELIAL DYSFUNCTION IMPROVEMENT

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    Mirjana Bakic

    2007-04-01

    Full Text Available Endothelium plays an important role in maintaining normal vascular tonus and blood fluidity reducing thrombocyte activity and adhesion of leukocytes as well as limiting response of vascular inflammation. However, in certain pathological conditions such as hypercholesterolemia, hypertension, and diabetes, endothelium improves vasoconstriction, inflammation and thrombocytic events.Non-pharmacological concept is based on recognition of genetic factors, environmental factors, or combination of risk factors for the occurrence of endothelial dysfunction, general and individual education of the significance of adequate nutrition, physical activity and regulation of body weight, regular check-ups and the application of antioxidants which can regulate and protect several aspects of endothelial functions.

  6. Capsaicinoids lower plasma cholesterol and improve endothelial function in hamsters.

    Science.gov (United States)

    Liang, Yin Tong; Tian, Xiao-Yu; Chen, Jing Nan; Peng, Cheng; Ma, Ka Ying; Zuo, Yuanyuan; Jiao, Rui; Lu, Ye; Huang, Yu; Chen, Zhen-Yu

    2013-02-01

    Capsaicinoids are the active compounds in chili pepper. The present study investigated the effect of capsaicinoids on plasma lipids, functionality of aorta including atherosclerotic plaque development, cholesterol absorption biomarker, fecal sterol excretion, and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism. Hamsters were divided into five groups and fed a high-cholesterol diet containing 0 % (CON), 0.010 % (LD), 0.015 % (MD), 0.020 % (HD), and 0.030 % (VD) capsaicinoids, respectively, for 6 weeks. Plasma lipids were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. Endothelial function was assessed by measuring the acetylcholine-induced endothelium-dependent relaxations in aorta. Capsaicinoids reduced plasma total cholesterol, non-high-density lipoprotein cholesterol, and triacylglycerols with high-density lipoprotein cholesterol being unaffected. All four experimental groups had a decrease in the atherosclerotic plaque compared with CON. Dietary capsaicinoids increased the fecal excretion of total acidic sterols possibly mediated by up-regulation of cholesterol 7α-hydroxylase and down-regulation of liver X receptor alpha. Plasma sterol analysis demonstrated that capsaicinoids decreased the ratio of plasma campesterol/cholesterol, suggesting they decreased cholesterol absorption. Capsaicinoids could improve the endothelium-dependent relaxations and reduce the endothelium-dependent contractions by inhibiting the gene expression of COX-2. However, no dose-dependent effect of capsaicinoids on these parameters was seen. Capsaicinoids were beneficial in improving lipoprotein profile and aortic function in hamsters fed a high-cholesterol diet.

  7. Some Phenolic Compounds Increase the Nitric Oxide Level in Endothelial Cells in Vitro

    NARCIS (Netherlands)

    Appeldoorn, M.M.; Venema, D.P.; Peters, T.H.F.; Koenen, M.E.; Arts, I.C.W.; Vincken, J.P.; Gruppen, H.; Keijer, J.; Hollman, P.C.H.

    2009-01-01

    The vasorelaxing properties of chocolate and wine might relate to the presence of phenolic compounds. One of the potential mechanisms involved is stimulation of endothelial nitric oxide (NO) production, as NO is a major regulator of vasodilatation. This study aimed to develop an in vitro assay using

  8. Some phenolic compounds increase the nitric oxide level in endothelial cells in vitro

    NARCIS (Netherlands)

    Appeldoorn, M.M.; Venema, D.P.; Peters, T.H.F.; Koenen, M.E.; Arts, I.C.W.; Vincken, J.-P.; Gruppen, H.; Keuer, J.; Hollman, P.C.H.

    2009-01-01

    The vasorelaxing properties of chocolate and wine might relate to the presence of phenolic compounds. One of the potential mechanisms involved is stimulation of endothelial nitric oxide (NO) production, as NO is a major regulator of vasodilatation. This study aimed to develop an in vitro assay using

  9. Extended incubation times improve corneal endothelial cell transplantation success.

    Science.gov (United States)

    Insler, M S; Lopez, J G

    1991-05-01

    To investigate the ability of extended incubation times to improve the success of endothelial cell transplantation, eight human donor corneas were denuded of their native endothelium, seeded twice during a 1-hr interval with a suspension of cultured infant human corneal endothelial cells, and then incubated for 144 hr under standard conditions. Subsequently the corneas were transplanted into African green monkeys using routine penetrating keratoplasty techniques. Rotational autografts and corneas devoid of endothelial cells served as controls. The seeded corneas appeared hazy at the time of surgery (mean pachymetry 48 hr postoperatively, 0.794 mm). Six corneas (75%) subsequently cleared, yielding a mean corneal thickness of 0.541 +/- 0.040 and 0.554 +/- 0.040 at 6 and 12 postoperative months, respectively. All control eyes showed advanced edema (thickness, greater than 1.0 mm) and developed extensive neovascularization. Clinically, the extended postseeding incubation corneas were observed to clear more rapidly and stabilize their thickness earlier than corneas incubated for only 24-48 hr. Scanning electron microscopy of extended postseeding incubation corneas revealed an intact monolayer of contact-inhibited cells with the hexagonal mosaic typical of corneal endothelium in vivo and improved intercellular contact compared with corneas incubated for only 24-48 hr.

  10. The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway

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    Beatriz Martínez-Poveda

    2012-09-01

    Full Text Available Aeroplysinin-1 is a brominated metabolite extracted from the marine sponge Aplysina aerophoba that has been previously characterized by our group as a potent antiangiogenic compound in vitro and in vivo. In this work, we provide evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial cells. Studies on the nuclear morphology of treated cells revealed that aeroplysinin-1 induces chromatin condensation and nuclear fragmentation, and it increases the percentage of cells with sub-diploid DNA content in endothelial, but not in HCT-116, human colon carcinoma and HT-1080 human fibrosarcoma cells. Treatment of endothelial cells with aeroplysinin-1 induces activation of caspases-2, -3, -8 and -9, as well as the cleavage of apoptotic substrates, such as poly (ADP-ribose polymerase and lamin-A in a caspase-dependent mechanism. Our data indicate a relevant role of the mitochondria in the apoptogenic activity of this compound. The observation that aeroplysinin-1 prevents the phosphorylation of Bad relates to the mitochondria-mediated induction of apoptosis by this compound.

  11. Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment.

    Science.gov (United States)

    Minozzo, Bruno Rodrigo; Fernandes, Daniel; Beltrame, Flávio Luís

    2018-01-17

    Endothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelial dysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed. Georg Thieme Verlag KG Stuttgart · New York.

  12. Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Lamy, Sylvie, E-mail: lamy.sylvie@uqam.ca; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

    2014-03-10

    Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

  13. Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function.

    Science.gov (United States)

    Joven, Jorge; March, Isabel; Espinel, Eugenia; Fernández-Arroyo, Salvador; Rodríguez-Gallego, Esther; Aragonès, Gerard; Beltrán-Debón, Raúl; Alonso-Villaverde, Carlos; Rios, Lidia; Martin-Paredero, Vicente; Menendez, Javier A; Micol, Vicente; Segura-Carretero, Antonio; Camps, Jordi

    2014-06-01

    Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. © 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation.

    Science.gov (United States)

    Lamy, Sylvie; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R

    2014-03-10

    Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Delayed onset of congenital hereditary endothelial dystrophy due to compound heterozygous SLC4A11 mutations

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    Babu Lal Kumawat

    2016-01-01

    Full Text Available Background: Congenital hereditary endothelial dystrophy (CHED is an autosomal recessive disorder characterized by bilateral, symmetrical, noninflammatory corneal clouding (edema present at birth or shortly thereafter. This study reports on an unusual delayed presentation of CHED with compound heterozygous SLC4A11 mutations. Materials and Methods: A 45-year-old female, presenting with bilateral decreased vision since childhood that deteriorated in the last 5 years, was evaluated to rule out trauma, viral illness, chemical injury, glaucoma, and corneal endothelial dystrophies. Tear sample was sent for herpes simplex viral (HSV antigen testing. Genomic DNA from peripheral blood was screened for mutations in all exons of SLC4A11 by direct sequencing. Full-thickness penetrating keratoplasty was done and corneal button was sent for histopathological examination. Results: Slit-lamp findings revealed bilateral diffuse corneal edema and left eye spheroidal degeneration with scarring. Increased corneal thickness (762 μm and 854 μm in the right and left eyes, respectively, normal intraocular pressure (12 mmHg and 16 mmHg in the right and left eyes, respectively, inconclusive confocal scan, and specular microscopy, near normal tear film parameters, were the other clinical features. HSV-polymerase chain reaction was negative. Histopathological examination revealed markedly thickened Descemet′s membrane with subepithelial spheroidal degeneration. SLC4A11 screening showed a novel variant p.Ser415Asn, reported mutation p.Cys386Arg and two polymorphisms, all in the heterozygous state and not identified in 100 controls. Conclusions: The study shows, for the first time, compound heterozygous SLC4A11 mutations impair protein function leading to delayed onset of the disease.

  16. Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art

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    Miroslav Radenković

    2013-01-01

    Full Text Available The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells’ count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

  17. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.

    Science.gov (United States)

    Alvarez, Roger A; Miller, Megan P; Hahn, Scott A; Galley, Joseph C; Bauer, Eileen; Bachman, Timothy; Hu, Jian; Sembrat, John; Goncharov, Dmitry; Mora, Ana L; Rojas, Mauricio; Goncharova, Elena; Straub, Adam C

    2017-12-01

    Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells (ECs) express hemoglobin (Hb) α to control nitric oxide (NO) diffusion, but the role of this system in pulmonary circulation has not been evaluated. We hypothesized that up-regulation of Hb α in pulmonary ECs contributes to NO depletion and pulmonary vascular dysfunction in pulmonary hypertension. Primary distal pulmonary arterial vascular smooth muscle cells, lung tissue sections from unused donor (control) and idiopathic pulmonary artery (PA) hypertension lungs, and rat and mouse models of SU5416/hypoxia-induced pulmonary hypertension (PH) were used. Immunohistochemical, immunocytochemical, and immunoblot analyses and transfection, infection, DNA synthesis, apoptosis, migration, cell count, and protein activity assays were performed in this study. Cocultures of human pulmonary microvascular ECs and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced PH were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study. We find increased expression of Hb α in pulmonary endothelium from humans and mice with PH compared with controls. In addition, we show up-regulation of Hb α in human pulmonary ECs cocultured with PA smooth muscle cells in hypoxia. We treated pulmonary ECs with a Hb α mimetic peptide that disrupts the association of Hb α with endothelial NO synthase, and found that cells treated with the peptide exhibited increased NO signaling compared with a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the Hb α mimetic peptide enhanced vasodilation in response to acetylcholine. Our findings reveal that endothelial Hb α functions as an endogenous scavenger of NO in the pulmonary endothelium

  18. Construction of extracellular microenvironment to improve surface endothelialization of NiTi alloy substrate

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Peng, E-mail: liupeng79@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433 (China); Zhao, Yongchun; Yan, Ying; Hu, Yan; Yang, Weihu [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Cai, Kaiyong, E-mail: kaiyong_cai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2015-10-01

    To mimic extracellular microenvironment of endothelial cell, a bioactive multilayered structure of gelatin/chitosan pair, embedding with vascular endothelial growth factor (VEGF), was constructed onto NiTi alloy substrate surface via a layer-by-layer assembly technique. The successful fabrication of the multilayered structure was demonstrated by scanning electron microscopy, atomic force microscopy, contact angle measurement, attenuated total reflection-fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The growth behaviors of endothelial cells on various NiTi alloy substrates were investigated in vitro. Cytoskeleton observation, MTT assay, and wound healing assay proved that the VEGF-embedded multilayer structure positively stimulated adhesion, proliferation and motogenic responses of endothelial cells. More importantly, the present system promoted the nitric oxide production of endothelial cells. The approach affords an alternative to construct extracellular microenvironment for improving surface endothelialization of a cardiovascular implant. - Highlights: • Biofunctional multilayer films mimicking extracellular microenvironment were successfully fabricated. • Multilayered structure stimulated the biological responses of endothelial cells. • The approach affords an efficient approach for surface endothelialization of stent implant.

  19. Weight loss improves biomarkers endothelial function and systemic ...

    African Journals Online (AJOL)

    ... while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. Conclusion: Weight loss ameliorates inflammatory cytokines and markers of endothelial function in obese postmenopausal Saudi women.

  20. Weight loss improves biomarkers endothelial function and systemic ...

    African Journals Online (AJOL)

    bariatric surgery decreased CRP ,IL-6 and increased the circulating level of adiponectin32-36. Reductions in pro- inflammatory cytokines concentrations after weight loss is explained by reduction in fat mass37. Concerning the markers of endothelial function, the ob- servation in this study indicated a significant reduction in.

  1. Ghrelin improves endothelial function in patients with metabolic syndrome.

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    Tesauro, Manfredi; Schinzari, Francesca; Iantorno, Micaela; Rizza, Stefano; Melina, Domenico; Lauro, Davide; Cardillo, Carmine

    2005-11-08

    Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin administration might beneficially affect endothelial function in metabolic syndrome. Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside (SNP), respectively, were assessed by strain-gauge plethysmography before and after local administration of human ghrelin (200 microg/min). During saline, the vasodilator response to acetylcholine was significantly blunted (P=0.008) in patients with metabolic syndrome (n=12, 5 female) compared with controls (n=12, 7 female), whereas the vasodilator response to SNP was not different between groups (P=0.68). In patients with metabolic syndrome, basal plasma ghrelin was significantly lower than in controls (P=0.02). In these patients, ghrelin infusion markedly increased intravascular concentrations of the peptide (Pghrelin had no effect on the vasodilator response to acetylcholine (P=0.78 versus saline) after nitric oxide inhibition by NG-monomethyl-L-arginine. These findings indicate that ghrelin reverses endothelial dysfunction in patients with metabolic syndrome by increasing nitric oxide bioactivity, thereby suggesting that decreased circulating levels of the peptide, such as those found in these patients, might play a role in the pathobiology of atherosclerosis.

  2. Forkhead box O-1 modulation improves endothelial insulin resistance in human obesity.

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    Karki, Shakun; Farb, Melissa G; Ngo, Doan T M; Myers, Samantha; Puri, Vishwajeet; Hamburg, Naomi M; Carmine, Brian; Hess, Donald T; Gokce, Noyan

    2015-06-01

    Increased visceral adiposity has been closely linked to insulin resistance, endothelial dysfunction, and cardiometabolic disease in obesity, but pathophysiological mechanisms are poorly understood. We sought to investigate mechanisms of vascular insulin resistance by characterizing depot-specific insulin responses and gain evidence that altered functionality of transcription factor forkhead box O-1 (FOXO-1) may play an important role in obesity-related endothelial dysfunction. We intraoperatively collected paired subcutaneous and visceral adipose tissue samples from 56 severely obese (body mass index, 43 ± 7 kg/m(2)) and 14 nonobese subjects during planned surgical operations, and characterized depot-specific insulin-mediated responses using Western blot and quantitative immunofluorescence techniques. Insulin signaling via phosphorylation of FOXO-1 and consequent endothelial nitric oxide synthase stimulation was selectively impaired in the visceral compared with subcutaneous adipose tissue and endothelial cells of obese subjects. In contrast, tissue actions of insulin were preserved in nonobese individuals. Pharmacological antagonism with AS1842856 and biological silencing using small interfering RNA-mediated FOXO-1 knockdown reversed insulin resistance and restored endothelial nitric oxide synthase activation in the obese. We observed profound endothelial insulin resistance in the visceral adipose tissue of obese humans which improved with FOXO-1 inhibition. FOXO-1 modulation may represent a novel therapeutic target to diminish vascular insulin resistance. In addition, characterization of endothelial insulin resistance in the adipose microenvironment may provide clues to mechanisms of systemic disease in human obesity. © 2015 American Heart Association, Inc.

  3. A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats.

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    Faria, Thaís de Oliveira; Angeli, Jhuli Keli; Mello, Luiz Guilherme Marchesi; Pinto, Gustavo Costa; Stefanon, Ivanita; Vassallo, Dalton Valentim; Lizardo, Juliana Hott de Fúcio

    2017-03-01

    Physical exercise is an important tool for the improvement of endothelial function. To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

  4. Arginase Inhibitor 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside Activates Endothelial Nitric Oxide Synthase and Improves Vascular Function.

    Science.gov (United States)

    Yi, Bonggu; Nguyen, Minh Cong; Won, Moo-Ho; Kim, Young Myeong; Ryoo, Sungwoo

    2017-02-01

    Endothelial arginase constrains the activity of endothelial nitric oxide synthase by reducing nitric oxide bioavailability, which contributes to vascular diseases. During screening, we identified a novel compound from the rhizome of Polygonum multiflorum (Polygonaceae), 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), which inhibited arginase activity. THSG exhibited noncompetitive inhibition of arginase II and inhibited both arginases I and II in a dose-dependent manner. THSG-dependent arginase inhibition reciprocally increased nitric oxide production and decreased reactive oxygen species generation in aortic endothelia. These effects were associated with increased dimerization of endothelial nitric oxide synthase without changes in the protein expression levels of arginase I, arginase II, or endothelial nitric oxide synthase. In vascular tension assays, when aortic vessels from wild-type mice are incubated with THSG, responses to the nitric oxide-dependent vasorelaxant acetylcholine were augmented, but responses to an nitric oxide donor, sodium nitroprusside, were not affected. On the other hand, phenylephrine-dependent vasoconstriction was significantly retarded in THSG-treated vessels. In a high-cholesterol diet-fed atherogenic model mice (ApoE-/-), THSG improved endothelial function by enhancement of the nitric oxide-cGMP pathway. Taken together, these results suggest that THSG may exert vasoprotective effects through augmentation of nitric oxide signaling by inhibiting arginase. Therefore, THSG may be useful in the treatment of vascular diseases that are derived from endothelial dysfunction, such as atherosclerosis. Georg Thieme Verlag KG Stuttgart · New York.

  5. Etanercept improves endothelial function via pleiotropic effects in rat adjuvant-induced arthritis.

    Science.gov (United States)

    Totoson, Perle; Maguin-Gaté, Katy; Prigent-Tessier, Anne; Monnier, Alice; Verhoeven, Frank; Marie, Christine; Wendling, Daniel; Demougeot, Céline

    2016-07-01

    To determine the effect of etanercept on endothelial dysfunction and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of arthritis, etanercept (10 mg/kg/3 days, s.c.) or saline was administered for 3 weeks in AIA rats. Body weights and arthritis scores were monitored daily. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclo-oxygenase (COX-2), arginase, endothelium-derived hyperpolarizing factor and superoxide anions (O2 (-)°) production. Aortic expression of endothelial nitic oxide synthase (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22(phox) and p47(phox) was evaluated by western blotting analysis. Blood pressure, heart rate and blood levels of triglycerides, cholesterol and glucose were measured. Etanercept significantly reduced arthritis score (P etanercept on inflammatory symptoms improved endothelial function in AIA. This beneficial effect on endothelial function is disconnected from its impact on CV risk factors and relates to pleiotropic effects of etanercept on endothelial pathways. These results suggest that etanercept could be a good choice for patients with rheumatoid arthritis at high risk of CV events. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Antihypertensive drugs methyldopa, labetalol, hydralazine, and clonidine improve trophoblast interaction with endothelial cellular networks in vitro.

    Science.gov (United States)

    Xu, Bei; Charlton, Francesca; Makris, Angela; Hennessy, Annemarie

    2014-05-01

    The interaction between trophoblasts and maternal endothelium is important for placental vascular modeling. Failure of uterine spiral artery transformation is linked to the etiopathology of preeclampsia. Antihypertensive medications used to control hypertension in early pregnancy can alter placental and circulating cytokines. This study investigated whether selected antihypertensive drugs can modulate the interaction between trophoblast and endothelial cells. Human uterine myometrial microvascular endothelial cells were preincubated with (or without) low-dose tumor necrosis factor-α (TNF-α; 0.5 ng/ml) or TNF-α and soluble fms-like tyrosine kinase 1 (sFlt-1; 100 ng/ml). Red fluorescent-labeled endothelial cells were then cultured on Matrigel. After appearance of endothelial cellular networks, green fluorescent-labeled HTR-8/SVneo trophoblast cells were cocultured in the presence of pharmacological doses of methyldopa, labetalol, hydralazine, and clonidine. Images were captured after 24 h and drug effects on HTR-8/SVneo cell integration were quantified by Image Analysis software. The conditioned medium was collected to measure sFlt-1, vascular endothelial growth factor (VEGF), placental growth factor, interleukin-10, and interleukin-6 by ELISA. Methyldopa, labetalol, hydralazine, and clonidine increased trophoblast integration into TNF-α-preincubated endothelial cellular networks. In conditioned medium, sFlt-1 was reduced by methyldopa, hydralazine, and clonidine alone. VEGF was increased by methyldopa. A decrease in placental growth factor was seen by methyldopa and also in nontreated endothelial cell coculture of the other three drugs. Some antihypertensive drugs used in pregnancy may improve the cellular interaction between trophoblast and endothelial cells exposed to TNF-α. Methyldopa, hydralazine, and clonidine reduced sFlt-1 concentration in culture medium, whereas labetalol increased trophoblast integration independently of sFlt-1. Methyldopa

  7. Omega-3 fatty acids plus rosuvastatin improves endothelial function in South Asians with dyslipidemia

    Directory of Open Access Journals (Sweden)

    Catalin Mindrescu

    2008-12-01

    Full Text Available Catalin Mindrescu1,2,3, Rakesh P Gupta1,3, Eileen V Hermance1, Mary C DeVoe1, Vikas R Soma1, John T Coppola1,2, Cezar S Staniloae1,21Comprehensive Cardiovascular Center, Saint Vincent’s Hospital Manhattan, New York, NY, USA; 2New York Medical College, Valhalla, NY, USA; 3Rakesh P Gupta and Catalin Mindrescu contributed equally to this article.Background: The present study was undertaken to investigate the effect of statins plus omega-3 polyunsaturated fatty acids (PUFAs on endothelial function and lipid profile in South Asians with dyslipidemia and endothelial dysfunction, a population at high risk for premature coronary artery disease.Methods: Thirty subjects were randomized to rosuvastatin 10 mg and omega-3-PUFAs 4 g or rosuvastatin 10 mg. After 4 weeks, omega-3-PUFAs were removed from the first group and added to subjects in the second group. All subjects underwent baseline, 4-, and 8-week assessment of endothelial function and lipid profile.Results: Compared to baseline, omega-3-PUFAs plus rosuvastatin improved endothelial-dependent vasodilation (EDV: −1.42% to 11.36%, p = 0.001, and endothelial-independent vasodilation (EIV: 3.4% to 17.37%, p = 0.002. These effects were lost when omega-3-PUFAs were removed (EDV: 11.36% to 0.59%, p = 0.003. In the second group, rosuvastatin alone failed to improve both EDV and EIV compared to baseline. However, adding omega-3-PUFAs to rosuvastatin, significantly improved EDV (−0.66% to 14.73%, p = 0.001 and EIV (11.02% to 24.5%, p = 0.001. Addition of omega-3-PUFAs further improved the lipid profile (triglycerides 139 to 91 mg/dl, p = 0.006, low-density lipoprotein cholesterol 116 to 88 mg/dl, p = 0.014.Conclusions: Combined therapy with omega-3-PUFAs and rosuvastatin improves endothelial function in South Asian subjects with dyslipidemia and endothelial dysfunction.Keywords: omega-3 fatty acids, endothelial function, South Asians, dyslipidemia, rosuvastatin

  8. Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation.

    Science.gov (United States)

    Salimi, Shabnam; Lewis, Joshua P; Yerges-Armstrong, Laura M; Mitchell, Braxton D; Saeed, Faisal; O'Connell, Jeffry R; Perry, James A; Ryan, Kathleen A; Shuldiner, Alan R; Parsa, Afshin

    2016-10-31

    Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function. Microcirculatory endothelial function was quantified by laser Doppler flowmetry (LDF) mediated by thermal hyperemia (TH) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post- versus preclopidogrel LDF measures. Preclopidogrel TH-LDF and platelet aggregation were higher in women than in men (PClopidogrel administration was associated with ≈2-fold higher percentage change in TH-LDF in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%, P=0.03). Clopidogrel also increased absolute TH-LDF measures in persons with high platelet aggregation (1757±766 to 2154±1055, P=0.03), with a more prominent effect in women (1909±846 to 2518±1048, P=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia LDF measures. The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

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    Christos Rammos

    Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

  10. Surface modification of hydrophobic polymers for improvement of endothelial cell-surface interactions

    NARCIS (Netherlands)

    Dekker, A.; Dekker, A.; Reitsma, K.; Beugeling, T.; Beugeling, T.; Bantjes, A.; Bantjes, A.; Feijen, Jan; Kirkpatrick, C.J.; van Aken, W.G.

    1992-01-01

    The aim of this study is to improve the interaction of endothelial cells with polymers used in vascular prostheses. Polytetrafluoroethylene (PTFE; Teflon) films were treated by means of nitrogen and oxygen plasmas. Depending on the plasma exposure time, modified PTFE surfaces showed water-contact

  11. Insulinlike Growth Factor-Binding Protein-1 Improves Vascular Endothelial Repair in Male Mice in the Setting of Insulin Resistance.

    Science.gov (United States)

    Aziz, Amir; Haywood, Natalie J; Cordell, Paul A; Smith, Jess; Yuldasheva, Nadira Y; Sengupta, Anshuman; Ali, Noman; Mercer, Ben N; Mughal, Romana S; Riches, Kirsten; Cubbon, Richard M; Porter, Karen E; Kearney, Mark T; Wheatcroft, Stephen B

    2018-02-01

    Insulin resistance is associated with impaired endothelial regeneration in response to mechanical injury. We recently demonstrated that insulinlike growth factor-binding protein-1 (IGFBP1) ameliorated insulin resistance and increased nitric oxide generation in the endothelium. In this study, we hypothesized that IGFBP1 would improve endothelial regeneration and restore endothelial reparative functions in the setting of insulin resistance. In male mice heterozygous for deletion of insulin receptors, endothelial regeneration after femoral artery wire injury was enhanced by transgenic expression of human IGFBP1 (hIGFBP1). This was not explained by altered abundance of circulating myeloid angiogenic cells. Incubation of human endothelial cells with hIGFBP1 increased integrin expression and enhanced their ability to adhere to and repopulate denuded human saphenous vein ex vivo. In vitro, induction of insulin resistance by tumor necrosis factor α (TNFα) significantly inhibited endothelial cell migration and proliferation. Coincubation with hIGFBP1 restored endothelial migratory and proliferative capacity. At the molecular level, hIGFBP1 induced phosphorylation of focal adhesion kinase, activated RhoA and modulated TNFα-induced actin fiber anisotropy. Collectively, the effects of hIGFBP1 on endothelial cell responses and acceleration of endothelial regeneration in mice indicate that manipulating IGFBP1 could be exploited as a putative strategy to improve endothelial repair in the setting of insulin resistance. Copyright © 2018 Endocrine Society.

  12. A novel compound, NP-184, inhibits the vascular endothelial growth factor induced angiogenesis.

    Science.gov (United States)

    Lin, Kuan-Ting; Lien, Jin-Cherng; Chung, Ching-Hu; Kuo, Sheng-Chu; Huang, Tur-Fu

    2010-03-25

    Angiogenesis is observed in many diseases, such as tumor progression, diabetes and rheumatoid arthritis; it is a process that involves proliferation, migration, differentiation and tube formation of endothelial cells. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by induction of these endothelial functions. Thus, inhibition of these critical angiogenic steps is a practical therapeutic strategy for those diseases. NP-184 is a substituted benzimidazole analogue which exhibits a potent anti-thrombotic activity. In this report, NP-184 inhibited the viability of human umbilical vascular endothelial cells (HUVEC) in a concentration-dependent manner, and caused cell apoptosis as examined by cell-cycle analysis and Annexin V staining with flow cytometry. NP-184 also concentration-dependently inhibited the HUVEC migration, tube formation on Matrigel, and rat aortic ring sprouting stimulated by VEGF. Regarding the intracellular signal transduction, NP-184 concentration-dependently interfered with the activation of AKT, ERK and the nuclear translocation of NF-kappaB. In vivo study showed that NP-184 dose-dependently reduced angiogenesis in Matrigel plug assay. These results indicate that NP-184 is a potential candidate for developing the treatment of angiogenesis related-diseases.

  13. Improving hemocompatibility and accelerating endothelialization of vascular stents by a copper-titanium film.

    Science.gov (United States)

    Liu, Hengquan; Pan, Changjiang; Zhou, Shijie; Li, Junfeng; Huang, Nan; Dong, Lihua

    2016-12-01

    Bio-inorganic films and drug-eluting coatings are usually used to improve the hemocompatibility and inhibit restenosis of vascular stent; however, above bio-performances couldn't combine together with single materials. In the present study, we reported a simple approach to fabricate a metal film with the aim of imparting the stent with good blood compatibility and accelerating endothelialization. The films with various ratios of Cu and Ti were prepared through the physical vapor deposition. Phase structure and element composition were investigated by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. The releasing volume of copper ion in Cu/Ti film was determined by immersing test. The hemolysis ratio, platelet adhesion and clotting time were applied to evaluate the hemocompatibility. The proliferative behaviors of endothelial cells and smooth muscle cells under certain copper concentration were investigated in vitro and in vivo. Results indicated that copper-titanium films exhibited good hemocompatibility in vitro; however, the increase of Cu/Ti ratio could lead to increasing hemolysis ratio. Endothelial cells displayed more proliferative than smooth muscle cells when the copper concentration was copper concentration was increased. The complete endothelialization of the film with low copper in vivo was observed at the 2nd week, indicating that the copper-titanium film with the lower copper concentration could promote endothelialization. Therefore, the inorganic copper-titanium film could be potential biomaterials to improve blood compatibility and accelerating endothelialization of vascular stents. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Amiloride Improves Endothelial Function and Reduces Vascular Stiffness in Female Mice Fed a Western Diet

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    Luis A. Martinez-Lemus

    2017-06-01

    Full Text Available Obese premenopausal women lose their sex related cardiovascular disease protection and develop greater arterial stiffening than age matched men. In female mice, we have shown that consumption of a Western diet (WD, high in fat and refined sugars, is associated with endothelial dysfunction and vascular stiffening, which occur via activation of mineralocorticoid receptors and associated increases in epithelial Na+ channel (ENaC activity on endothelial cells (EnNaC. Herein our aim was to determine the effect that reducing EnNaC activity with a very-low-dose of amiloride would have on decreasing endothelial and arterial stiffness in young female mice consuming a WD. To this end, we fed female mice either a WD or control diet and treated them with or without a very-low-dose of the ENaC-inhibitor amiloride (1 mg/kg/day in the drinking water for 20 weeks beginning at 4 weeks of age. Mice consuming a WD were heavier and had greater percent body fat, proteinuria, and aortic stiffness as assessed by pulse-wave velocity than those fed control diet. Treatment with amiloride did not affect body weight, body composition, blood pressure, urinary sodium excretion, or insulin sensitivity, but significantly reduced the development of endothelial and aortic stiffness, aortic fibrosis, aortic oxidative stress, and mesenteric resistance artery EnNaC abundance and proteinuria in WD-fed mice. Amiloride also improved endothelial-dependent vasodilatory responses in the resistance arteries of WD-fed mice. These results indicate that a very-low-dose of amiloride, not affecting blood pressure, is sufficient to improve endothelial function and reduce aortic stiffness in female mice fed a WD, and suggest that EnNaC-inhibition may be sufficient to ameliorate the pathological vascular stiffening effects of WD-induced obesity in females.

  15. A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats

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    Thaís de Oliveira Faria

    Full Text Available Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR. Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS, phosphorylated endothelial nitric oxide synthase (p-eNOS1177 and inducible nitric oxide synthase (iNOS and to generate concentration-response curves to acetylcholine (ACh and to phenylephrine (PHE. The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME and indomethacin administration. The maximal response (Emax and the sensitivity (EC50 to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex rats (Emax= -80 ± 4.6%, p < 0.05 when compared to those of controls (Ct (Emax = -50 ± 6.8%. The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05 when compared to control conditions (120 ± 4.2%. This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05. Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

  16. Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity.

    Science.gov (United States)

    Hughes-Large, Jennifer M; Pang, Dominic K T; Robson, Debra L; Chan, Pak; Toma, Jelena; Borradaile, Nica M

    2014-12-01

    Niacin (nicotinic acid) as a monotherapy can reduce vascular disease risk, but its mechanism of action remains controversial, and may not be dependent on systemic lipid modifying effects. Niacin has recently been shown to improve endothelial function and vascular regeneration, independent of correcting dyslipidemia, in rodent models of vascular injury and metabolic disease. As a potential biosynthetic precursor for NAD(+), niacin could elicit these vascular benefits through NAD(+)-dependent, sirtuin (SIRT) mediated responses. Alternatively, niacin may act through its receptor, GPR109A, to promote endothelial function, though endothelial cells are not known to express this receptor. We hypothesized that niacin directly improves endothelial cell function during exposure to lipotoxic conditions and sought to determine the potential mechanism(s) involved. Angiogenic function in excess palmitate was assessed by tube formation following treatment of human microvascular endothelial cells (HMVEC) with either a relatively low concentration of niacin (10 μM), or nicotinamide mononucleotide (NMN) (1 μM), a direct NAD(+) precursor. Although both niacin and NMN improved HMVEC tube formation during palmitate overload, only NMN increased cellular NAD(+) and SIRT1 activity. We further observed that HMVEC express GRP109A. Activation of this receptor with either acifran or MK-1903 recapitulated niacin-induced improvements in HMVEC tube formation, while GPR109A siRNA diminished the effect of niacin. Niacin, at a low concentration, improves HMVEC angiogenic function under lipotoxic conditions, likely independent of NAD(+) biosynthesis and SIRT1 activation, but rather through niacin receptor activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Small and Intermediate Calcium-Activated Potassium Channel Openers Improve Rat Endothelial and Erectile Function

    Science.gov (United States)

    Comerma-Steffensen, Simon G.; Carvacho, Ingrid; Hedegaard, Elise R.; Simonsen, Ulf

    2017-01-01

    Modulation of endothelial calcium-activated potassium (KCa) channels has been proposed as an approach to restore endothelial function. The present study investigated whether novel openers of KCa channels with small (KCa2.x) and intermediate (KCa3.1) conductance, NS309 and NS4591, improve endothelium-dependent relaxation and erectile function. Rat corpus cavernosum (CC) strips were mounted for isometric tension recording and processed for immunoblotting. Mean arterial pressure (MAP), intracavernosal pressure (ICP), and electrocardiographic (ECG) measurements were conducted in anesthetized rats. Immunoblotting revealed the presence of KCa2.3 and large KCa conductance (KCa1.1) channels in the corpus cavernosum. NS309 and NS4591 increased current in CC endothelial cells in whole cell patch clamp experiments. Relaxation induced by NS309 (cavernous nerve stimulation with NS309 were unchanged, whereas NS4591 significantly improved erectile function. Administration of NS309 and NS4591 caused small changes in the electrocardiogram, but neither arrhythmic events nor prolongation of the QTc interval were observed. The present study suggests that openers of KCa2.x and KCa3.1 channels improve endothelial and erectile function. The effects of NS309 and NS4591 on heart rate and ECG are small, but will require additional safety studies before evaluating whether activation of KCa2.3 channels has a potential for treatment of erectile dysfunction. PMID:28993731

  18. Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

    Science.gov (United States)

    Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

    2015-12-30

    recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment. Kefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.

  19. A single consumption of curry improved postprandial endothelial function in healthy male subjects: a randomized, controlled crossover trial.

    Science.gov (United States)

    Nakayama, Hideki; Tsuge, Nobuaki; Sawada, Hiroshi; Masamura, Noriya; Yamada, Shohei; Satomi, Shigeki; Higashi, Yukihito

    2014-06-28

    Curry, one of the most popular foods in Japan, contains spices that are rich in potentially antioxidative compounds, such as curcumin and eugenol. Oxidative stress is thought to impair endothelial function associated with atherosclerosis, a leading cause of cardiovascular events. The aim of this study was to determine whether a single consumption of curry meal would improve endothelial function in healthy men. Fourteen healthy male subjects (BMI 23.7 ± 2.7 kg/m2; age 45 ± 9 years) were given a single serving of curry meal or spice-free control meal (180 g of curry or control and 200 g of cooked rice; approximately 500 kcal in total) in a randomized, controlled crossover design. Before and 1 hr after the consumption, fasting and postprandial flow-mediated vasodilation (FMD) responses and other parameters were measured. The consumption of the control meal decreased FMD from 5.8 ± 2.4% to 5.1 ± 2.3% (P = 0.039). On the other hand, the consumption of the curry meal increased FMD from 5.2 ± 2.5% to 6.6 ± 2.0% (P = 0.001), and the postprandial FMD after the curry meal was higher than that after the control meal (P = 0.002). Presence of spices in the curry did not alter significantly the systemic and forearm hemodynamics, or any biochemical parameters including oxidative stress markers measured. These findings suggest that the consumption of curry ameliorates postprandial endothelial function in healthy male subjects and may be beneficial for improving cardiovascular health. UMIN Clinical Trials Registry 000012012.

  20. Propranolol treatment lowers blood pressure, reduces vascular inflammatory markers and improves endothelial function in obese mice.

    Science.gov (United States)

    da Silva Franco, Nathalia; Lubaczeuski, Camila; Guizoni, Daniele M; Victorio, Jamaira A; Santos-Silva, Junia C; Brum, Patricia C; Carneiro, Everardo M; Davel, Ana P

    2017-08-01

    Obesity-associated hypertension is accompanied by a number of cardiovascular risk factors including vascular insulin resistance (IR) and higher sympathetic nervous activity. Therefore, autonomic blockade was demonstrated to reverse hypertension, endothelial dysfunction and IR in obese individuals. We hypothesized that β-AR blockade with propranolol would restore endothelial function and vascular insulin signaling in obesity, associated with an anti-inflammatory effect. Body weight, systolic blood pressure (SBP), plasma biochemical parameters and aortic endothelial function were analyzed in mice fed standard diet (control group) or a high fat diet (HFD) that were treated with vehicle (water) or propranolol (10mg/kg/day) for 8weeks. Propranolol treatment did not modify obesogenic effect of HFD feeding. However, propranolol was effective in preventing the rise in SBP, the hyperinsulinemia and the impaired endothelium-dependent relaxation to acetylcholine and to insulin in obese mice. Protective effect of propranolol administration in endothelial function was associated with increased nitric oxide (NO) production and phosphorylation of Akt (Ser473) and eNOS (Ser1177), but with reduced phospho-IRS-1(Ser307) and phospho-ERK1/2 (Thr202/Tyr204). In addition, β-blocker propranolol prevented the NF-kB nuclear translocation and the increase in phospho-IκB-α (Ser32) and in interleukin(IL)-6 expression in aorta of obese mice, without significant changes in either aortic reactive oxygen species production or in circulating IL-6 and TNF-α levels. In β2-AR knockout mice, despite increasing body weight and visceral fat, HFD did not increase SBP and showed a partial improvement of endothelial function, revealing a role of β2-AR in cardiovascular effects of obesity. In conclusion, our results suggest that β-AR blockade with propranolol is effective to prevent the endothelial dysfunction, vascular IR and pro-inflammatory state displayed in HFD-induced obesity, independent of

  1. Small and Intermediate Calcium-Activated Potassium Channel Openers Improve Rat Endothelial and Erectile Function

    Directory of Open Access Journals (Sweden)

    Simon G. Comerma-Steffensen

    2017-09-01

    Full Text Available Modulation of endothelial calcium-activated potassium (KCa channels has been proposed as an approach to restore endothelial function. The present study investigated whether novel openers of KCa channels with small (KCa2.x and intermediate (KCa3.1 conductance, NS309 and NS4591, improve endothelium-dependent relaxation and erectile function. Rat corpus cavernosum (CC strips were mounted for isometric tension recording and processed for immunoblotting. Mean arterial pressure (MAP, intracavernosal pressure (ICP, and electrocardiographic (ECG measurements were conducted in anesthetized rats. Immunoblotting revealed the presence of KCa2.3 and large KCa conductance (KCa1.1 channels in the corpus cavernosum. NS309 and NS4591 increased current in CC endothelial cells in whole cell patch clamp experiments. Relaxation induced by NS309 (<1 μM was inhibited by endothelial cell removal and high extracellular potassium. An inhibitor of nitric oxide (NO synthase, and blockers of KCa2.x and KCa1.1 channels, apamin and iberiotoxin also inhibited NS309 relaxation. Incubation with NS309 (0.5 μM markedly enhanced acetylcholine relaxation. Basal erectile function (ICP/MAP increased during administration of NS309. Increases in ICP/MAP after cavernous nerve stimulation with NS309 were unchanged, whereas NS4591 significantly improved erectile function. Administration of NS309 and NS4591 caused small changes in the electrocardiogram, but neither arrhythmic events nor prolongation of the QTc interval were observed. The present study suggests that openers of KCa2.x and KCa3.1 channels improve endothelial and erectile function. The effects of NS309 and NS4591 on heart rate and ECG are small, but will require additional safety studies before evaluating whether activation of KCa2.3 channels has a potential for treatment of erectile dysfunction.

  2. Metformin Improves Endothelial Function and Reduces Blood Pressure in Diabetic Spontaneously Hypertensive Rats Independent from Glycemia Control : Comparison to Vildagliptin

    NARCIS (Netherlands)

    Hamidi Shishavan, Mahdi; Henning, Robert H; van Buiten, Azuwerus; Goris, Maaike; Deelman, Leo E; Buikema, Hendrik

    2017-01-01

    Metformin confers vascular benefits beyond glycemia control, possibly via pleiotropic effects on endothelial function. In type-1-diabetes-mellitus (T1DM-)patients metformin improved flow-mediated dilation but also increased prostaglandin(PG)-F-2 alpha, a known endothelial-contracting factor. To

  3. Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Y. Liang

    2015-06-01

    Full Text Available Remote ischemic preconditioning (RIPre can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG surgery were assigned randomly to a RIPre group (n=20 or coronary heart disease (CHD group (n=20. Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD, CD34+ monocyte count, and endothelial nitric oxide synthase (eNOS expression. Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05 and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05. RIPre activated STAT-3 and increased CD34+ endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells.

  4. Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Y.; Li, Y.P.; He, F.; Liu, X.Q.; Zhang, J.Y. [Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2015-04-28

    Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34{sup +} monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34{sup +} endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells.

  5. In vitro biocompatibility and endothelialization of novel magnesium-rare Earth alloys for improved stent applications.

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    Full Text Available Magnesium (Mg based alloys are the most advanced cardiovascular stent materials. This new generation of stent scaffold is currently under clinical evaluation with encouraging outcomes. All these Mg alloys contain a certain amount of rare earth (RE elements though the exact composition is not yet disclosed. RE alloying can usually enhance the mechanical strength of different metal alloys but their toxicity might be an issue for medical applications. It is still unclear how RE elements will affect the magnesium (Mg alloys intended for stent materials as a whole. In this study, we evaluated MgZnCaY-1RE, MgZnCaY-2RE, MgYZr-1RE, and MgZnYZr-1RE alloys for cardiovascular stents applications regarding their mechanical strength, corrosion resistance, hemolysis, platelet adhesion/activation, and endothelial biocompatibility. The mechanical properties of all alloys were significantly improved. Potentiodynamic polarization showed that the corrosion resistance of four alloys was at least 3-10 times higher than that of pure Mg control. Hemolysis test revealed that all the materials were non-hemolytic while little to moderate platelet adhesion was found on all materials surface. No significant cytotoxicity was observed in human aorta endothelial cells cultured with magnesium alloy extract solution for up to seven days. Direct endothelialization test showed that all the alloys possess significantly better capability to sustain endothelial cell attachment and growth. The results demonstrated the promising potential of these alloys for stent material applications in the future.

  6. In Vitro Biocompatibility and Endothelialization of Novel Magnesium-Rare Earth Alloys for Improved Stent Applications

    Science.gov (United States)

    Zhao, Nan; Watson, Nevija; Xu, Zhigang; Chen, Yongjun; Waterman, Jenora; Sankar, Jagannathan; Zhu, Donghui

    2014-01-01

    Magnesium (Mg) based alloys are the most advanced cardiovascular stent materials. This new generation of stent scaffold is currently under clinical evaluation with encouraging outcomes. All these Mg alloys contain a certain amount of rare earth (RE) elements though the exact composition is not yet disclosed. RE alloying can usually enhance the mechanical strength of different metal alloys but their toxicity might be an issue for medical applications. It is still unclear how RE elements will affect the magnesium (Mg) alloys intended for stent materials as a whole. In this study, we evaluated MgZnCaY-1RE, MgZnCaY-2RE, MgYZr-1RE, and MgZnYZr-1RE alloys for cardiovascular stents applications regarding their mechanical strength, corrosion resistance, hemolysis, platelet adhesion/activation, and endothelial biocompatibility. The mechanical properties of all alloys were significantly improved. Potentiodynamic polarization showed that the corrosion resistance of four alloys was at least 3–10 times higher than that of pure Mg control. Hemolysis test revealed that all the materials were non-hemolytic while little to moderate platelet adhesion was found on all materials surface. No significant cytotoxicity was observed in human aorta endothelial cells cultured with magnesium alloy extract solution for up to seven days. Direct endothelialization test showed that all the alloys possess significantly better capability to sustain endothelial cell attachment and growth. The results demonstrated the promising potential of these alloys for stent material applications in the future. PMID:24921251

  7. Effects of improved glycaemic control on endothelial function in patients with type 2 diabetes.

    Science.gov (United States)

    Bagg, W; Whalley, G A; Gamble, G; Drury, P L; Sharpe, N; Braatvedt, G D

    2001-08-01

    Patients with type 2 diabetes have abnormal endothelial function but it is not certain whether improvements in glycaemic control will improve endothelial function. To examine the effects of short-term improved glycaemic control on endothelial function in patients with inadequately regulated type 2 diabetes mellitus. Forty-three patients with type 2 diabetes and glycosylated haemoglobin (HbA1c) > 8.9% were randomized to either improved glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Using high-resolution B-mode ultrasound, brachial artery flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN-D) were measured at baseline and 20 weeks later. After 20 weeks, HbA1c was significantly lower in IC versus UC (IC 8.02 +/- 0.25% versus UC 10.23 +/- 0.23%, P < 0.0001) but changes in FMD and GTN-D were not different between the groups (FMD at baseline and week 20 IC 5.1 +/- 0.56% versus 4.9 +/- 0.56% and UC 4.2 +/- 0.51% versus 3.1 +/- 0.51%; P = 0.23: GTN-D IC 12.8 +/- 1.34% versus 10.4 +/- 1.32% and UC 13.7 +/- 1.2% versus 12.7 +/- 1.23%; P = 0.39). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks compared to 0.02 +/- 0.70 kg in UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in either group. Short-term reduction of HbA1c levels did not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control.

  8. Improving the characterization of endothelial progenitor cell subsets by an optimized FACS protocol.

    Directory of Open Access Journals (Sweden)

    Karin Huizer

    Full Text Available The characterization of circulating endothelial progenitor cells (EPCs is fundamental to any study related to angiogenesis. Unfortunately, current literature lacks consistency in the definition of EPC subsets due to variations in isolation strategies and inconsistencies in the use of lineage markers. Here we address critical points in the identification of hematopoietic progenitor cells (HPCs, circulating endothelial cells (CECs, and culture-generated outgrowth endothelial cells (OECs from blood samples of healthy adults (AB and umbilical cord (UCB. Peripheral blood mononuclear cells (PBMCs were enriched using a Ficoll-based gradient followed by an optimized staining and gating strategy to enrich for the target cells. Sorted EPC populations were subjected to RT-PCR for tracing the expression of markers beyond the limits of cell surface-based immunophenotyping. Using CD34, CD133 and c-kit staining, combined with FSC and SSC, we succeeded in the accurate and reproducible identification of four HPC subgroups and found significant differences in the respective populations in AB vs. UCB. Co-expression analysis of endothelial markers on HPCs revealed a complex pattern characterized by various subpopulations. CECs were identified by using CD34, KDR, CD45, and additional endothelial markers, and were subdivided according to their apoptotic state and expression of c-kit. Comparison of UCB-CECs vs. AB-CECs revealed significant differences in CD34 and KDR levels. OECs were grown from PBMC-fractions We found that viable c-kit+ CECs are a candidate circulating precursor for CECs. RT-PCR to angiogenic factors and receptors revealed that all EPC subsets expressed angiogenesis-related molecules. Taken together, the improvements in immunophenotyping and gating strategies resulted in accurate identification and comparison of better defined cell populations in a single procedure.

  9. Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

    Science.gov (United States)

    Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

    2011-01-01

    Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

  10. Treatment with acarbose may improve endothelial dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Vallejo, S; Angulo, J; Peiró, C; Cercas, E; Sánchez-Ferrer, A; Nevado, J; Llergo, J L; Rodríguez-Mañas, L; Sánchez-Ferrer, C F

    2000-08-01

    We sought to determine whether a single reduction of hyperglycemia and those derivatives from nonenzymatic protein glycosylation may be effective in reducing the development of diabetic endothelial dysfunction. Therefore, we investigated how acarbose, an inhibitor of intestinal alpha-glucosidase that reduce hyperglycemia by lowering glucose absorption, may prevent the impairment of acetylcholine (ACh)-induced endothelium-dependent relaxations observed in isolated vascular segments from untreated streptozotocin-induced diabetic rats. When administered after diabetes induction, 10 mg/kg acarbose decreased modestly the enhancement of blood glucose and glycosylated hemoglobin (HbA1c) levels, but not those of advanced glycosylation end products (AGEs). This effect was linked to a partial improvement of ACh-induced responses both in conductance vessels, such as aortic segments, and resistance vasculature, like mesenteric microvessels. When acarbose was introduced after 6 weeks of untreated diabetes, blood glucose, HbA1c, and AGE levels were not affected and endothelial dysfunction remained unchanged in mesenteric microvessels, whereas a small improvement was observed in aortic segments. The addition of 100 U/ml superoxide dismutase enhanced the impaired relaxations to values similar to vessels from nondiabetic rats, indicating a main role for superoxide anions in diabetes-induced endothelial dysfunction. We conclude that hyperglycemia itself or elevated HbA1c, but not plasma AGEs, are related to enhanced oxidative stress and to the impairment of endothelium function associated to diabetes. This process can be partially prevented by reducing glucose absorption with acarbose.

  11. Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

    Directory of Open Access Journals (Sweden)

    Ronaldo Altenburg Gismondi

    2015-01-01

    Full Text Available AbstractBackground:Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.Objective:To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.Methods:Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring, endothelial function (brachial artery flow-mediated dilation, and vascular stiffness (pulse wave velocity were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively.Results:The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007, and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003 when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820. There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586.Conclusion:Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

  12. Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.

    Science.gov (United States)

    McLaughlin, Kelsey; Baczyk, Dora; Potts, Audrey; Hladunewich, Michelle; Parker, John D; Kingdom, John C P

    2017-01-01

    Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability. © 2016 American Heart Association, Inc.

  13. Moderate-intensity endurance training improves endothelial glycocalyx layer integrity in healthy young men.

    Science.gov (United States)

    Majerczak, Joanna; Grandys, Marcin; Duda, Krzysztof; Zakrzewska, Agnieszka; Balcerczyk, Aneta; Kolodziejski, Leszek; Szymoniak-Chochol, Dorota; Smolenski, Ryszard T; Bartosz, Grzegorz; Chlopicki, Stefan; Zoladz, Jerzy A

    2017-01-01

    What is the central question of this study? The main aim of the present study was to determine the effect of prolonged moderate-intensity endurance training on the endothelial glycocalyx layer integrity in relationship to the training-induced changes in oxidative stress and antioxidant defence in humans. What is the main finding and its importance? We have shown, for the first time, a protective effect of prolonged moderate-intensity endurance training on endothelial glycocalyx layer integrity, as judged by significantly lower basal and end-exercise serum concentrations of glycocalyx damage markers, i.e. syndecan-1 and heparan sulfate, accompanied by attenuation of oxidative stress and enhancement of antioxidant defence after training in previously untrained healthy young men. In this study, we evaluated the effect of 20 weeks of moderate-intensity endurance training (ET) on the endothelial glycocalyx layer integrity in relationship to the training-induced changes in antioxidant defence. Eleven healthy young, untrained men performed an incremental cycling exercise bout until exhaustion before and after 20 weeks of ET. Endurance training consisted of 40 min sessions, mainly of moderate intensity (∼50% of maximal oxygen uptake), performed four times per week. Venous blood samples were taken at rest and at the end of the maximal exercise test. Muscle biopsies from vastus lateralis were taken before and after the training. Endurance training resulted in a significant increase in physical capacity (P Training led to a decrease (P training did not induce a significant increase in basal nitrite/nitrate plasma concentration (P > 0.05). Moderate-intensity ET exerts a pronounced protective effect on endothelial glycocalyx integrity at rest and during exercise, probably through an improvement of antioxidant defence that may represent the vasoprotective mechanisms highly responsive to moderate-intensity endurance training. © 2016 The Authors. Experimental Physiology

  14. Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi; Sun, Li; Zhang, Song; Wang, Dingyu; Liu, Zhaorui; Yuan, Yue; Liu, Yang [Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province (China); Li, Yue, E-mail: ly99ly@vip.163.com [Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province (China); Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province (China)

    2016-05-20

    Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. -- Highlights: •Geraniol improved endothelial dependent relaxation in high fat diet fed mice. •Geraniol alleviated vascular injury in high fat diet fed mice. •Geraniol inhibited ROS generation through downregulating NOX-2 expression.

  15. In vitro Spatial Compound Scanning for Improved Visualization of Atherosclerosis

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh; Wilhjelm, Jens E.; Sillesen, Henrik

    2000-01-01

    A new off-line multiangle ultrasound (US) compound scanner has been built with the purpose of investigating possible improvements in visualization of vascular structure. Images of two formalin-fixed human atherosclerotic plaques removed by carotid endarterectomy were recorded from seven insonific......A new off-line multiangle ultrasound (US) compound scanner has been built with the purpose of investigating possible improvements in visualization of vascular structure. Images of two formalin-fixed human atherosclerotic plaques removed by carotid endarterectomy were recorded from seven...

  16. Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Verhoeven, F; Totoson, P; Maguin-Gaté, K; Prigent-Tessier, A; Marie, C; Wendling, D; Moretto, J; Prati, C; Demougeot, C

    2017-05-01

    To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions ( O2-°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22(phox) and p47(phox) was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O2-° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O2-° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on

  17. Netrin-1 Promotes Inflammation Resolution to Achieve Endothelialization of Small-Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ.

    Science.gov (United States)

    Li, Yanzhao; Wan, Simin; Liu, Ge; Cai, Wang; Huo, Da; Li, Gang; Yang, Mingcan; Wang, Yuxin; Guan, Ge; Ding, Ning; Liu, Feila; Zeng, Wen; Zhu, Chuhong

    2017-12-01

    The transplant of small-diameter tissue engineering blood vessels (small-diameter TEBVs) (vascular replacement therapy often fails because of early onset thrombosis and long-standing chronic inflammation. The specific inflammation state involved in small-diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small-diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin-1) is found present in endothelial cells of natural blood vessels and has anti-inflammatory effects. This work generates netrin-1-modified small-diameter TEBVs by using layer-by-layer self-assembly to resolve the inflammation. The results show that netrin-1 reprograms macrophages (MΦ) to assume an anti-inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small-diameter TEBVs modified by netrin-1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small-diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ-derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.

  18. Can fish oil supplementation improve endothelial function in asymptomatic offspring of patients with peripheral arterial disease?

    Directory of Open Access Journals (Sweden)

    Spark JI

    2013-07-01

    Full Text Available J Ian Spark,1 Christopher L Delaney,1 Richard B Allan,1 Melissa HL Ho,2 Michelle D Miller21Department of Vascular Surgery, Flinders Medical Centre and Flinders University, 2Department of Nutrition and Dietetics, Flinders University, Bedford Park, Adelaide, South Australia, AustraliaBackground: Peripheral arterial disease affects 10%–25% of adults aged .55 years, and while a multitude of risk factors exist, one key influence is genetics. Rather than awaiting the onset of debilitating symptoms, interventions that target high-risk individuals and prevent or delay the onset of symptoms would have widespread impact. The aim of this study is to implement a 12-week fish oil intervention (10 mL/day containing approximately 1.5 g of eicosapentaenoic acid and 1 g of docosahexaenoic acid, with the intention of improving endothelial function, inflammation, and lipid status in a high-risk population, ie, those with impaired endothelial function and a parent with symptomatic peripheral arterial disease.Methods: This is a parallel-group, double-blind, randomized controlled trial involving administration of fish oil containing either about 1.5 g of docosahexaenoic acid and 1 g of docosahexaenoic acid (intervention or about 0.15 g of eicosapentaenoic acid and about 0.1 g of docosahexaenoic acid for 12 consecutive weeks (control. The participants are 100 offspring of adults with diagnosed peripheral arterial disease who themselves have an ankle-brachial pressure index ≥0.9 but impaired endothelial function according to peripheral arterial tonometry. Measures performed at baseline and at 6 and 12 weeks include flow-mediated dilatation, C-reactive protein, absolute neutrophil and lymphocyte counts, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels, thromboxane and prostacyclin, lipid status, and homocysteine, nitrite, and nitrate levels. Participants will be phoned fortnightly to monitor adherence and side effects, while participants will

  19. Fenofibrate and extended-release niacin improve the endothelial protective effects of HDL in patients with metabolic syndrome.

    Science.gov (United States)

    Gomaraschi, Monica; Ossoli, Alice; Adorni, Maria Pia; Damonte, Elisabetta; Niesor, Eric; Veglia, Fabrizio; Franceschini, Guido; Benghozi, Renee; Calabresi, Laura

    2015-11-01

    Fibrates and niacin are at present the most effective therapies to increase plasma levels of high density lipoprotein-cholesterol (HDL-C); to date, limited data are available on their effects on HDL protective functions. Within a multicenter, randomized, open-label, cross-over study, 37 patients with metabolic syndrome received 6weeks' treatment with fenofibrate or extended-release niacin (ER niacin), with a 4weeks' wash-out period. HDL ability to preserve endothelial cell homeostasis was assessed by incubating cultured endothelial cells with HDL isolated from patients at baseline and after each treatment. HDL isolated from patients at baseline were as effective as control HDL in inhibiting vascular cell adhesion molecule-1 (VCAM-1) expression, but less efficient in promoting endothelial cell nitric oxide (NO) release. Both fenofibrate and ER niacin increased HDL ability to inhibit TNFα-induced VCAM-1 expression (+7% and +11%, respectively). Fenofibrate and ER niacin also improved the impaired HDL ability to induce the expression of endothelial nitric oxide synthase and NO production (+10% and +8%, respectively). Interestingly, HDL isolated after treatment showed an ability to promote endothelial NO release similar to HDL isolated from controls. No differences were observed between the two drugs. With both drugs, HDL function was improved irrespective of baseline HDL-C levels. Treatment with fenofibrate or ER niacin in patients with metabolic syndrome not only increased HDL-C levels but also improved the endothelial protective effects of HDL. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Vascular endothelial function is improved by oral glycine treatment in aged rats.

    Science.gov (United States)

    Gómez-Zamudio, Jaime H; García-Macedo, Rebeca; Lázaro-Suárez, Martha; Ibarra-Barajas, Maximiliano; Kumate, Jesús; Cruz, Miguel

    2015-06-01

    Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15 months of age. Concentration-response curves to phenylephrine (PHE) were obtained from aortic rings incubated with N(G)-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT-PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

  1. Κ-opioid receptor stimulation improves endothelial function in hypoxic pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Qi Wu

    Full Text Available The present study was designed to investigate the effect of κ-opioid receptor stimulation with U50,488H on endothelial function and underlying mechanism in rats with hypoxic pulmonary hypertension (HPH. Chronic hypoxia-induced HPH was simulated by exposing the rats to 10% oxygen for 2 wk. After hypoxia, mean pulmonary arterial pressure (mPAP, right ventricular pressure (RVP and right ventricular hypertrophy index (RVHI were measured. Relaxation of pulmonary artery in response to acetylcholine (ACh was determined. Expression and activity of endothelial nitric oxide (NO synthase (eNOS and inducible NO synthase (iNOS with NO production, total antioxidant capacity (T-AOC, gp91(phox expression and nitrotyrosine content were measured. The effect of U50,488H administration during chronic hypoxia was investigated. Administration of U50,488H significantly decreased mPAP and right ventricular hypertrophy as evidenced by reduction in RVP and RVHI. These effects were mediated by κ-opioid receptor. In the meantime, treatment with U50,488H significantly improved endothelial function as evidenced by enhanced relaxation in response to ACh. Moreover, U50,488H resulted in a significant increase in eNOS phosphorylation, NO content in serum, and T-AOC in pulmonary artery of HPH rats. In addition, the activity of eNOS was enhanced, but the activity of iNOS was attenuated in the pulmonary artery of chronic hypoxic rats treated with U50,488H. On the other hand, U50,488H markedly blunted HPH-induced elevation of gp91(phox expression and nitrotyrosine content in pulmonary artery, and these effects were blocked by nor-BNI, a selective κ-opioid receptor antagonist. These data suggest that κ-opioid receptor stimulation with U50,488H improves endothelial function in rats with HPH. The mechanism of action might be attributed to the preservation of eNOS activity, enhancement of eNOS phosphorylation, downregulation of iNOS activity and its antioxidative/nitrative effect.

  2. A Novel Poly-Naphthol Compound ST104P Suppresses Angiogenesis by Attenuating Matrix Metalloproteinase-2 Expression in Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Yi-Ling Ma

    2014-09-01

    Full Text Available Angiogenesis, the process of neovascularization, plays an important role in physiological and pathological conditions. ST104P is a soluble polysulfated-cyclo-tetrachromotropylene compound with anti-viral and anti-thrombotic activities. However, the functions of ST104P in angiogenesis have never been explored. In this study, we investigated the effects of ST104P in angiogenesis in vitro and in vivo. Application of ST104P potently suppressed the microvessels sprouting in aortic rings ex vivo. Furthermore, ST104P treatment significantly disrupted the vessels’ development in transgenic zebrafish in vivo. Above all, repeated administration of ST104P resulted in delayed tumor growth and prolonged the life span of mice bearing Lewis lung carcinoma. Mechanistic studies revealed that ST104P potently inhibited the migration, tube formation and wound closure of human umbilical endothelial cells (HUVECs. Moreover, ST104P treatment inhibited the secretion and expression of matrix metalloproteinase-2 (MMP-2 in a dose-dependent manner. Together, these results suggest that ST104P is a potent angiogenesis inhibitor and may hold potential for treatment of diseases due to excessive angiogenesis including cancer.

  3. Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Veronica Tisato

    2013-01-01

    Full Text Available Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD and thrombosis; thus to characterize CVD vein endothelial cells (VEC has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n=31 in CVD patients’ plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF-α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES, we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES. Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that α-Lipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.

  4. Supervised physical exercise improves endothelial function in patients with systemic lupus erythematosus.

    Science.gov (United States)

    dos Reis-Neto, Edgard Torres; da Silva, Aline Evelyn; Monteiro, Carlos Manoel de Castro; de Camargo, Luciano Monteiro; Sato, Emilia Inoue

    2013-12-01

    The objective of this study was to evaluate the effect of supervised physical exercise on endothelial function, ergospirometric test variables and disease activity in SLE patients. We conducted a prospective study in which women with SLE who were available to perform physical exercise were allocated to the exercise group (EG) to practise supervised physical exercise for 1 h three times per week for 16 weeks. Those who were not available for this activity were allocated to the control group (CG). Intervention consisted of walking at a heart rate corresponding to the ventilatory 1 threshold obtained from ergospirometry and monitored by a frequency meter. At baseline (T0) and after 16 weeks (T16), patients were assessed for endothelial function by brachial artery (flow-mediated dilation), ergospirometry and disease activity (SLEDAI). Statistical analysis was performed through normality tests, Student's t-test and non-parametric tests for data with non-normal distribution. P exercise tolerance [12.3 (2.4) vs 13.4 (2.6) min, P = 0.027], maximum speed [7.7 (1.0) vs 8.3 (1.2) km/h, P = 0.027] and threshold speed [5.6 (0.7) vs 6.1 (0.9) km/h, P = 0.005] in the EG without a difference in the CG. There was no difference in the SLEDAI score in both groups. Physical exercise is a useful strategy to improve endothelial function and aerobic capacity without worsening disease activity in SLE patients. TRIAL REGISTRATION; ClinicalTrials.gov (http://www.clinicaltrials.gov), NCT01712529.

  5. Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats.

    Science.gov (United States)

    Vilskersts, Reinis; Kuka, Janis; Svalbe, Baiba; Cirule, Helena; Liepinsh, Edgars; Grinberga, Solveiga; Kalvinsh, Ivars; Dambrova, Maija

    2011-01-01

    Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronate, an inhibitor of L-carnitine biosynthesis, or their combination on the development of hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Experimental animals were divided into five groups and treated for 8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at the doses above (n = 10). During the experiment, control group animals continued to consume a diet with normal salt content. Administration of the combination significantly improved the survival rate for 50% of the population. None of the tested compounds or their combination influenced high salt intake-induced hypertension, while treatment with mildronate and the combination for 8 weeks significantly decreased resting heart rate by 12% and 10%, respectively. Feeding with high salt diet had no influence on systolic function of the heart, but it induced thickening of the ventricular walls and development of heart hypertrophy that was not improved by the administration of tested compounds. In addition, administration of the combination attenuated the development of endothelial dysfunction in isolated aortic rings. In conclusion, our results demonstrate that treatment with a combination of L-carnitine and mildronate is protective against hypertension-induced complications in an experimental model of salt-induced hypertension.

  6. Nicotine promotes vascular endothelial growth factor secretion by human trophoblast cells under hypoxic conditions and improves the proliferation and tube formation capacity of human umbilical endothelial cells.

    Science.gov (United States)

    Zhao, Hongbo; Wu, Lanxiang; Wang, Yahui; Zhou, Jiayi; Li, Ruixia; Zhou, Jiabing; Wang, Zehua; Xu, Congjian

    2017-04-01

    Pre-eclampsia, characterized as defective uteroplacental vascularization, remains the major cause of maternal and fetal mortality and morbidity. Previous epidemiological studies demonstrated that cigarette smoking reduced the risk of pre-eclampsia. However, the molecular mechanism remains elusive. In the present study, it is demonstrated that a low dose of nicotine decreased soluble vascular endothelial growth factor receptor 1 (sFlt1) secretion in human trophoblast cells under hypoxic conditions. Nicotine was then observed to promote vascular endothelial growth factor (VEGF) secretion by reducing sFlt1 secretion and increasing VEGF mRNA transcription. Further data showed that nicotine enhanced hypoxia-mediated hypoxia-inducible factor-1α (HIF-1α) expression and HIF-1α small interfering RNA abrogated nicotine-induced VEGF secretion, indicating that HIF-1α may be responsible for nicotine-mediated VEGF transcription under hypoxic conditions. Moreover, conditioned medium from human trophoblast cells treated with nicotine under hypoxic conditions promoted the proliferation and tube formation capacity of human umbilical endothelial cells (HUVEC) by promoting VEGF secretion. These findings indicate that nicotine may promote VEGF secretion in human trophoblast cells under hypoxic conditions by reducing sFlt1 secretion and up-regulating VEGF transcription and improve the proliferation and tube formation of HUVEC cells, which may contribute to elucidate the protective effect of cigarette smoking against pre-eclampsia. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

    Science.gov (United States)

    Jokura, Hiroko; Watanabe, Isamu; Umeda, Mika; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension.

    Science.gov (United States)

    Perros, Frédéric; Ranchoux, Benoît; Izikki, Mohamed; Bentebbal, Sana; Happé, Chris; Antigny, Fabrice; Jourdon, Philippe; Dorfmüller, Peter; Lecerf, Florence; Fadel, Elie; Simonneau, Gerald; Humbert, Marc; Bogaard, Harm Jan; Eddahibi, Saadia

    2015-02-24

    Endothelial cell (EC) dysfunction plays a central role in the pathogenesis of pulmonary arterial hypertension (PAH), promoting vasoconstriction, smooth muscle proliferation, and inflammation. This study sought to test the hypothesis that nebivolol, a β1-antagonist and β2,3-agonist, may improve PAH and reverse the PAH-related phenotype of pulmonary ECs (P-EC). We compared the effects of nebivolol with metoprolol, a first-generation β1-selective β-blocker, on human cultured PAH and control P-EC proliferation, vasoactive and proinflammatory factor production, and crosstalk with PA smooth muscle cells. We assessed the effects of both β-blockers in precontracted PA rings. We also compared the effects of both β-blockers in experimental PAH. PAH P-ECs overexpressed the proinflammatory mediators interleukin-6 and monocyte chemoattractant protein-1, fibroblast growth factor-2, and the potent vasoconstrictive agent endothelin-1 as compared with control cells. This pathological phenotype was corrected by nebivolol but not metoprolol in a dose-dependent fashion. We confirmed that PAH P-EC proliferate more than control cells and stimulate more PA smooth muscle cell mitosis, a growth abnormality that was normalized by nebivolol but not by metoprolol. Nebivolol but not metoprolol induced endothelium-dependent and nitric oxide-dependent relaxation of PA. Nebivolol was more potent than metoprolol in improving cardiac function, pulmonary vascular remodeling, and inflammation of rats with monocrotaline-induced pulmonary hypertension. Nebivolol could be a promising option for the management of PAH, improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function. Until clinical studies are undertaken, however, routine use of β-blockers in PAH cannot be recommended. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Improvement of Lesion Detection by Complete Angular Compound Ultrasonic Elastography.

    Science.gov (United States)

    Liu, Chenhui; Zhou, Yufeng

    2016-01-24

    Quasi -: static ultrasound elastography is an emerging diagnostic imaging modality for determining the stiffness of pathologically changed soft tissues, which do not show significant differences in acoustic impedance for B-mode imaging. Although some methods were applied to improve the signal-to-noise ratio (SNRe) and contrast-to-noise ratio (CNRe) of the constructed elastogram, nonuniform strain distribution at the internal boundary of a hard inclusion, even with the uniform displacement on the surface, is an inherent mechanical effect and results in distortion at the detected lesion boundary. To overcome such stress concentrations, a new elastographic modality was proposed, where the elastograms from different angles throughout 360° were compounded. The strain field and subsequent ultrasound images were calculated using the finite element method (FEM) and Field II, respectively, from which the elastograms were constructed. The performance of complete angular compound elastography with varied interval angles, lesion sizes, and ratios of Young's moduli of the lesion to the background was simulated and compared with that of conventional axial strain elastography. It is found that viewing the lesion from only about 10 angles (interval of 36°) would significantly improve the image quality of elastogram (increasing SNRe by at least 13% and CNRe by at least 5.8 dB), reduce the lesion distortion in the lateral direction, and enhance the sensitivity, resolution, and accuracy of lesion detection. A preliminary phantom study showed similar improvements. Altogether, complete angular compound elastography improves the elastogram quality and reduces the mechanical effects in lesion detection. © The Author(s) 2016.

  10. Bradykinin preconditioning improves therapeutic potential of human endothelial progenitor cells in infarcted myocardium.

    Directory of Open Access Journals (Sweden)

    Zulong Sheng

    Full Text Available OBJECTIVES: Stem cell preconditioning (PC is a powerful approach in reducing cell death after transplantation. We hypothesized that PC human endothelial progenitor cells (hEPCs with bradykinin (BK enhance cell survival, inhibit apoptosis and repair the infarcted myocardium. METHODS: The hEPCs were preconditioned with or without BK. The hEPCs apoptosis induced by hypoxia along with serum deprivation was determined by annexin V-fluorescein isothiocyanate/ propidium iodide staining. Cleaved caspase-3, Akt and eNOS expressions were determined by Western blots. Caspase-3 activity and vascular endothelial growth factor (VEGF levels were assessed in hEPCs. For in vivo studies, the survival and cardiomyocytes apoptosis of transplanted hEPCs were assessed using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodi- carbocyanine,4-chlorobenzenesul-fonate salt labeled hEPCs and TUNEL staining. Infarct size and cardiac function were measured at 10 days after transplantation, and the survival of transplanted hEPCs were visualized using near-infrared optical imaging. RESULTS: In vitro data showed a marked suppression in cell apoptosis following BK PC. The PC reduced caspase-3 activation, increased the Akt, eNOS phosphorylation and VEGF levels. In vivo data in preconditioned group showed a robust cell anti-apoptosis, reduction in infarct size, and significant improvement in cardiac function. The effects of BK PC were abrogated by the B2 receptor antagonist HOE140, the Akt and eNOS antagonists LY294002 and L-NAME, respectively. CONCLUSIONS: The activation of B2 receptor-dependent PI3K/Akt/eNOS pathway by BK PC promotes VEGF secretion, hEPC survival and inhibits apoptosis, thereby improving cardiac function in vivo. The BK PC hEPC transplantation for stem cell-based therapies is a novel approach that has potential for clinical used.

  11. Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women.

    Science.gov (United States)

    Wang-Polagruto, Janice F; Villablanca, Amparo C; Polagruto, John A; Lee, Luke; Holt, Roberta R; Schrader, Heather R; Ensunsa, Jodi L; Steinberg, Francene M; Schmitz, Harold H; Keen, Carl L

    2006-01-01

    Endothelial dysfunction characterizes many disease states including subclinical atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal, healthy individuals when administered either acutely or over a period of several days, or weeks. Women experience increased risk for cardiovascular disease after menopause, which can be associated with endothelial dysfunction. Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known. The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women. Thirty-two postmenopausal hypercholesterolemic women were randomly assigned to consume a high-flavanol cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low-flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a double-blind study (n=16 per group). Endothelial function was determined by brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite, activation of cellular adhesion markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function and reactivity. Changes in these plasma markers were then correlated to brachial reactivity. Brachial artery hyperemic blood flow increased significantly by 76% (Pflavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women. In addition, our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved

  12. Recombinant human activated protein C improves endotoxemia-induced endothelial dysfunction: a blood-free model in isolated mouse arteries.

    Science.gov (United States)

    Sennoun, Nacira; Baron-Menguy, Celine; Burban, Mélanie; Lecompte, Thomas; Andriantsitohaina, Ramaroson; Henrion, Daniel; Mercat, Alain; Asfar, Pierre; Levy, Bruno; Meziani, Ferhat

    2009-07-01

    Recombinant human activated protein C (rhAPC) is one of the treatment panels for improving vascular dysfunction in septic patients. In a previous study, we reported that rhAPC treatment in rat endotoxemia improved vascular reactivity, although the mechanisms involved are still under debate. In the present study, we hypothesized that rhAPC may improve arterial dysfunction through its nonanticoagulant properties. Ten hours after injection of LPS in mice (50 mg/kg ip), aortic rings and mesenteric arteries were isolated and incubated with or without rhAPC for 12 h. Aortic rings were mounted in a myograph, after which arterial contractility and endothelium-dependent relaxation were measured in the presence or absence of nitric oxide synthase or cyclooxygenase inhibitors. Flow (shear stress)-mediated dilation with or without the above inhibitors was also measured in mesenteric resistance arteries. Protein expression was assessed by Western blotting. Lipopolysaccharide (LPS) reduced aortic contractility to KCl and phenylephrine as well as dilation to acetylcholine. LPS also reduced flow-mediated dilation in mesenteric arteries. In rhAPC-treated aorta and mesenteric arteries, contractility and endothelial responsiveness to vasodilator drug and shear stress were improved. rhAPC treatment also improved LPS-induced endothelial dysfunction; this effect was associated with an increase in the phosphorylated form of endothelial nitric oxide synthase and protein kinase B as well as cyclooxygenase vasodilatory pathways, thus suggesting that these pathways, together with the decrease in nuclear factor-kappaB activation and inducible nitric oxide synthase expression in the vascular wall, are implicated in the endothelial effect of rhAPC. In conclusion, ex vivo application of rhAPC improves arterial contractility and endothelial dysfunction resulting from endotoxemia in mice. This finding provides important insights into the mechanism underlying rhAPC-induced improvements on arterial

  13. Seven-day remote ischemic preconditioning improves local and systemic endothelial function and microcirculation in healthy humans.

    NARCIS (Netherlands)

    Jones, H.; Hopkins, N.; Bailey, T.G.; Green, D.J.; Cable, N.T.; Thijssen, D.H.J.

    2014-01-01

    BACKGROUND: Ischemic preconditioning (IPC) protects tissue against ischemia-induced injury inside and outside ischemic areas. The purpose was to examine the hypothesis that daily IPC leads to improvement in endothelial function and skin microcirculation not only in the arm exposed to IPC but also in

  14. Oligonucleotide and Parylene Surface Coating of Polystyrene and ePTFE for Improved Endothelial Cell Attachment and Hemocompatibility

    Directory of Open Access Journals (Sweden)

    Martina Schleicher

    2012-01-01

    Full Text Available In vivo self-endothelialization by endothelial cell adhesion on cardiovascular implants is highly desirable. DNA-oligonucleotides are an intriguing coating material with nonimmunogenic characteristics and the feasibility of easy and rapid chemical fabrication. The objective of this study was the creation of cell adhesive DNA-oligonucleotide coatings on vascular implant surfaces. DNA-oligonucleotides immobilized by adsorption on parylene (poly(monoaminomethyl-para-xylene coated polystyrene and ePTFE were resistant to high shear stress (9.5 N/m2 and human blood serum for up to 96 h. Adhesion of murine endothelial progenitor cells, HUVECs and endothelial cells from human adult saphenous veins as well as viability over a period of 14 days of HUVECs on oligonucleotide coated samples under dynamic culture conditions was significantly enhanced (P<0.05. Oligonucleotide-coated surfaces revealed low thrombogenicity and excellent hemocompatibility after incubation with human blood. These properties suggest the suitability of immobilization of DNA-oligonucleotides for biofunctionalization of blood vessel substitutes for improved in vivo endothelialization.

  15. Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

    2017-08-15

    Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

  16. Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

    OpenAIRE

    Sin Bond Leung; Huina Zhang; Chi Wai Lau; Yu Huang; Zhixiu Lin

    2013-01-01

    Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunc...

  17. Acarbose, an alpha-glucosidase inhibitor, improves endothelial dysfunction in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.

    Science.gov (United States)

    Azuma, Kosuke; Toyofuku, Yukiko; Iesaki, Takafumi; Otsuka, Aiko; Tanaka, Atsuko; Mita, Tomoya; Hirose, Takahisa; Tanaka, Yasushi; Daida, Hiroyuki; Kawamori, Ryuzo; Watada, Hirotaka

    2006-06-30

    Several epidemiological studies have revealed that subjects with postprandial hyperglycemia are at increased risk of cardiovascular disease. However, the impact of postprandial hyperglycemia and its treatment on endothelial function has not been clarified yet. In this study, Goto-Kakizaki (GK) rats, a non-obese type 2 diabetes model, fed twice daily were used as a model of repetitive postprandial glucose spikes. We investigated the endothelial function in these rats treated or untreated with acarbose, an alpha-glucosidase inhibitor. Administration of acarbose for 12 weeks markedly improved postprandial hyperglycemia, postprandial insulin level, total cholesterol, triglyceride, and free fatty acid level in GK rats. Furthermore, acarbose efficiently reduced the number of monocytes adherent to aortic endothelial layer, improved acetylcholine-dependent vasodilatation, and reduced intimal thickening of the aorta. While it is generally regarded that repetitive postprandial hyperglycemia is associated with the onset of cardiovascular diseases, our data demonstrated that acarbose treatment efficiently ameliorated endothelial dysfunction and reduced intimal thickening, thus adding support to the protective effect of acarbose against the onset of cardiovascular disease.

  18. Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease.

    Science.gov (United States)

    Willoughby, Scott R; Luu, Lee-Jen; Cameron, James D; Nelson, Adam J; Schultz, Carlee D; Worthley, Stephen G; Worthley, Matthew I

    2014-06-01

    Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease. This benefit may be due to effects not exclusively related to platelet aggregation. The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease (CAD). Forty subjects with stable CAD were randomised to clopidogrel therapy (75mg/day) or control. Blood and endothelial function testing occurred at baseline, one week and three months following randomisation. Microvascular endothelial function was assessed via reactive hyperaemic index (RHI). Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow™ system. Plasma markers of endothelial function (asymmetric dimethylarginine, ADMA) and oxidative stress (myeloperoxidase, MPO) were also tested. The primary endpoint was endothelial function assessment (RHI) at three months. At one week RHI increased by 20±10% in the clopidogrel group; this effect was maintained at three months (21±9% increase from baseline; Pmicrovascular endothelial function in patients with stable CAD. This effect is independent of its effects on ADP-induced platelet reactivity. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  19. Effect of diet-induced weight loss on endothelial dysfunction: early improvement after the first week of dieting.

    Science.gov (United States)

    Mavri, Alenka; Poredoš, Peter; Suran, David; Gaborit, Benedicte; Juhan-Vague, Irène; Poredoš, Pavel

    2011-01-01

    Obesity is associated with impaired endothelial function, and this may lead to increased cardiovascular risk. To gain insight into the beneficial effects of diet-induced weight loss on endothelial function, endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery and several metabolic and inflammatory markers were assessed in 40 obese women (BMI 34.9 ± 4.88 kg/m(2)) at baseline, after the 1st week and after 5 months on a low-calorie diet of 5.0 MJ/day. Twenty lean women served as controls. At entry, the obese women had a lower FMD than the lean women (7.7 ± 1.8 vs. 11.5 ± 4.2%, p dieting and continued during the following months of this simple non-pharmacological lifestyle modification to reach normalisation of endothelial function. The favourable effect of dieting on endothelial function is independent of the accompanying improvement of classical risk factors.

  20. Metformin Improves Endothelial Function and Reduces Blood Pressure in Diabetic Spontaneously Hypertensive Rats Independent from Glycemia Control: Comparison to Vildagliptin.

    Science.gov (United States)

    Hamidi Shishavan, Mahdi; Henning, Robert H; van Buiten, Azuwerus; Goris, Maaike; Deelman, Leo E; Buikema, Hendrik

    2017-09-08

    Metformin confers vascular benefits beyond glycemia control, possibly via pleiotropic effects on endothelial function. In type-1-diabetes-mellitus (T1DM-)patients metformin improved flow-mediated dilation but also increased prostaglandin(PG)-F2α, a known endothelial-contracting factor. To explain this paradoxical finding we hypothesized that metformin increased endothelial-vasodilator mediators (e.g. NO and EDHF) to an even larger extent. Spontaneously-hypertensive-rats (SHR) display impaired endothelium-dependent relaxation (EDR) involving contractile PGs. EDR was studied in isolated SHR aortas and the involvement of PGs, NO and EDHF assessed. 12-week metformin 300 mg/kg/day improved EDR by up-regulation of NO and particularly EDHF; it also reduced blood pressure and increased plasma sulphide levels (a proxy for H2S, a possible mediator of EDHF). These effects persisted in SHR with streptozotocin (STZ)-induced T1DM. Vildagliptin (10 mg/kg/day), targeting the incretin axis by increasing GLP-1, also reduced blood pressure and improved EDR in SHR aortas, mainly via the inhibition of contractile PGs, but not in STZ-SHR. Neither metformin nor vildagliptin altered blood glucose or HbA1c. In conclusion, metformin reduced blood pressure and improved EDR in SHR aorta via up-regulation of NO and particularly EDHF, an effect that was independent from glycemia control and maintained during T1DM. A comparison to vildagliptin did not support effects of metformin mediated by GLP-1.

  1. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study

    National Research Council Canada - National Science Library

    Sola, Srikanth; Mir, Muhammad Q S; Cheema, Faiz A; Khan-Merchant, Nadya; Menon, Rekha G; Parthasarathy, Sampath; Khan, Bobby V

    2005-01-01

    .... We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome...

  3. Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure.

    Science.gov (United States)

    Stauffer, Brian L; Dow, Caitlin A; Diehl, Kyle J; Bammert, Tyler D; Greiner, Jared J; DeSouza, Christopher A

    2017-11-09

    Vascular endothelial fibrinolytic function is impaired in adults with prehypertension and hypertension and plays a mechanistic role in the development of atherothrombotic events. The influence of β-blockers on endothelial fibrinolysis is unknown. This study compared the effects of chronic nebivolol and metoprolol treatment on endothelial tissue-type plasminogen activator (t-PA) release in adults with elevated blood pressure (BP). Forty-four middle-aged adults (36% women) with elevated BP completed a 3-month, double-blind, randomized, placebo-controlled trial comparing nebivolol (5 mg/d), metoprolol succinate (100 mg/d), and placebo. Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside before and after each intervention. In a subset, the dose-response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C. At baseline, resting BP and endothelial t-PA release were comparable between the 3 groups. BP decreased to a similar extent (≈10 mm Hg) in the nebivolol- and metoprolol-treated groups. There was a substantial increase (≈30%; PURL: http://www.clinicaltrials.gov. Unique identifier: NCT01595516. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. Chronic black tea extract consumption improves endothelial function in ovariectomized rats.

    Science.gov (United States)

    Leung, Fung Ping; Yung, Lai Ming; Ngai, Ching Yuen; Cheang, Wai San; Tian, Xiao Yu; Lau, Chi Wai; Zhang, Yang; Liu, Jian; Chen, Zhen Yu; Bian, Zhao-Xiang; Yao, Xiaoqiang; Huang, Yu

    2016-08-01

    Menopause escalates the risk of cardiovascular diseases in women. There is an unmet need for better treatment strategy for estrogen-deficiency-related cardiovascular complications. Here we investigated the impact of chronic black tea extract (BT) consumption on cardiovascular function and lipid metabolism using a rat model of estrogen deficiency. Female Sprague-Dawley rats were ovariectomized (OVX) and treated with BT (15 mg/kg/day, 4 weeks; active ingredients: theaflavins) or estrogen (E2) treatment for 4 weeks. Serum was collected for measuring cholesterol, triacylglycerol and estradiol levels. Changes in vascular reactivity were examined. The protein levels of NADPH oxidases were assessed by Western blotting. Reactive oxygen species (ROS) level was measured using dihydroethidium fluorescence imaging. The concentrations of cGMP were measured using ELISA kit. Aortic rings from control, BT-treated and E2-treated OVX rats exhibited a greater increase in Phe-induced contraction after inhibition of NO synthase compared with those from OVX rats. ACh-induced endothelium-dependent relaxations were augmented in aortae and renal arteries in BT/E2-treated OVX rats than in OVX rats. BT/E2 treatment improved flow-mediated dilatation in small mesenteric resistance arteries of OVX rats. BT/E2 treatment restored the eNOS phosphorylation level and reversed the up-regulation of NADPH oxidases and ROS overproduction in OVX rat aortae. ACh-stimulated cGMP production was significantly elevated in the aortae from BT- and E2-treated rats compared with those from OVX rats. BT/E2 treatment reduced circulating levels of total cholesterol. The present study reveals the novel benefits of chronic BT consumption to reverse endothelial dysfunction and favorably modifying cholesterol profile in a rat model of estrogen deficiency and provides insights into developing BT as beneficial dietary supplements for postmenopausal women.

  5. Topical negative pressure stimulates endothelial migration and proliferation: a suggested mechanism for improved integration of Integra.

    Science.gov (United States)

    Baldwin, Christopher; Potter, Matthew; Clayton, Elizabeth; Irvine, Laurie; Dye, Julian

    2009-01-01

    Topical negative pressure is an effective technique to promote wound healing and the integration of skin graft and synthetic dermal equivalents. We describe an in vitro model to investigate the effect of negative pressure on angiogenesis, a pivotal step. Dermal fibroblasts or human microvascular endothelial cells were cultured on Integra and subjected to intermittent or continuous negative pressure. At fixed intervals of over 120 hours, the Integra was fixed and assessed for cell migration (microscopy), cell viability (MTS assay), and cell proliferation (Ki67 immunostaining). Under control conditions, endothelial cells formed a monolayer and failed to ingress, whereas fibroblasts migrated throughout the Integra within 24 hours. Negative pressure switches endothelial cell to a migratory and proliferative phenotype. Ingress is greatest with intermittent rather than continuous negative pressure. It has no effect on dermal fibroblast function. This study identifies an important, potential pro-angiogenic mechanism by which topical negative pressure promotes wound healing.

  6. Extended-release niacin/laropiprant improves endothelial function in patients after myocardial infarction.

    Science.gov (United States)

    Bregar, Urska; Jug, Borut; Keber, Irena; Cevc, Matija; Sebestjen, Miran

    2014-05-01

    Raising high-density lipoprotein cholesterol (HDL-C) is an important strategy for reducing residual cardiovascular risk. In the present study, we sought to assess the effect of extended-release niacin/laropiprant on endothelial function in patients after a myocardial infarction with target low-density lipoprotein cholesterol (LDL-C). In this double-blind, placebo-controlled trial, 63 men (35-60 years of age) after a myocardial infarction were randomized to either niacin/laropiprant (1000/20 mg daily for 4 weeks and 2000/40 mg daily thereafter) or placebo. Flow-mediated dilation (FMD) and nitroglycerin-induced (GTN) dilation of the brachial artery, total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), lipoprotein(a) [Lp(a)], and apolipoprotein (Apo) A1/B were measured at baseline and after 12 weeks of intervention. FMD significantly increased (from 3.9 ± 5.1 to 9.8 ± 4.4%, p niacin/laropiprant group, but not in the placebo group (4.6 ± 4.4 to 6.1 ± 4.4%, p = 0.16) (p = 0.02 for comparison of interventions). GTN dilation also increased in the niacin/laropiprant group (from 12.5 ± 6.1 to 16.7 ± 4.8%, p = 0.02), but not in the placebo group (13.4 ± 5.0 to 15.1 ± 5.2%, p = 0.18), (p = 0.60 for comparison of interventions). Niacin/laropiprant reduced TC and LDL-C (p = 0.05 for both) and increased HDL-C (p niacin/laropiprant group, with no difference in the placebo group. ApoA1 did not change in either of the groups (p = 0.13; p = 0.26). FMD and GTN dilation improvements did not correlate with changes in the lipid profile. Niacin/laropiprant improves endothelium-dependent and endothelium-independent dilation of the brachial artery. This improvement does not correlate with changes in lipid parameters.

  7. Methotrexate improves perivascular adipose tissue/endothelial dysfunction via activation of AMPK/eNOS pathway.

    Science.gov (United States)

    Ma, Yanmin; Li, Li; Shao, Yating; Bai, Xiaohong; Bai, Tiao; Huang, Xinliang

    2017-04-01

    Adipose and endothelial dysfunction is associated with cardiovascular disease. Perivascular adipose tissue (PVAT) directly surrounds vessels and influences vessel function via a paracrine effect, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) modulates the metabolic pathway, thus, the present study hypothesized that activation of AMPK in PVAT may regulate endothelial function in pathological settings. The present study investigated the effect of methotrexate (MTX) on adipocytokine expression in PVAT with an emphasis on the regulation of endothelial function. The effects of MTX and the mechanisms involved were investigated using a relaxation assay and western blot analysis. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels. ELISA assay was used to quantify the level of TNF‑α and IL‑6. Palmitic acid (PA) stimulation induced inflammation and dysregulation of adipocytokine expression in PVAT. MTX treatment inhibited nuclear factor‑κB p65 phosphorylation and downregulated expression of pro‑inflammatory cytokines, including tumor necrosis factor‑α and interleukin-6, whereas adiponectin expression increased. MTX increased AMPK phosphorylation under basal and inflammatory conditions in PVAT, whereas knockdown of AMPK via small interfering RNA diminished its modulatory effect, indicating that MTX inhibits inflammation in an AMPK‑dependent manner. The present study prepared conditioned medium from PA‑stimulated PVAT to induce endothelial dysfunction and observed that pre‑treatment of PVAT with MTX effectively restored the loss of acetylcholine‑induced vasodilation and increased endothelial nitric oxide synthase phosphorylation in the rat aorta. The results of the present study demonstrated that MTX ameliorated inflammation-associated adipocytokine dysregulation and thus prevented endothelial dysfunction. These data provide further

  8. Xuebijing injection reduces organ injuries and improves survival by attenuating inflammatory responses and endothelial injury in heatstroke mice.

    Science.gov (United States)

    Xu, Qiulin; Liu, Jingxian; Guo, Xiaohua; Tang, Youqing; Zhou, Gengbiao; Liu, Yanan; Huang, Qiaobing; Geng, Yan; Liu, Zhifeng; Su, Lei

    2015-02-05

    The pathogenesis of heatstroke is a multi-factorial process involved with an interplay among subsequent inflammation, endothelial injury and coagulation disturbances, which makes pharmacological therapy of heatstroke a challenging problem. Xuebijing injection (XBJ), a traditional Chinese medicine used to sepsis, has been reported to suppress inflammatory responses and restore coagulation disturbances. However, little is known about the role of XBJ in heatstroke. Mice were treated with indicated dose of XBJ before and/or after the induction of heatstroke. Serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and endothelial markers, von Willebrand Factor (vWF) and E-selectin, were measured by ELISA. Liver, kidney and heart profiles including alanine aminotransferase, aspartic aminotransferase, creatinine, blood urea nitrogen, and lactate dehydrogenase, were evaluated by UniCel DxC 800 Synchron Clinical Systems, and troponin was measured by ELISA. Coagulation profiles, including thrombin time, prothrombin time, activated partial thromboplastin time, international normalized ratio, and fibrinogen were examined by STA Compact® Hemostasis System. Jejunum injury was evaluated with H&E staining. Changes in mitochondrial structure in cardiac tissue were assesed by electron microscopy. Pretreatment with XBJ decreased serum pro-inflammatory cytokines including TNF-α and IL-6, as well as endothelial injury markers, vWF and E-selectin, in a dose-dependent manner in heatstroke mice. Similar protective effects were observed when XBJ was administered after, or both before and after heat insult. These protective effects lasted for over 12 h in mice receiving XBJ before and after heat insult. XBJ also improved survival rates in heatstroke mice, ameliorated liver, heart, and kidney injuries, including mitochondrial damage to the heart, and reduced coagulation disturbances. XBJ prevents organ injuries and improves survival in heatstroke mice by

  9. Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Sin Bond Leung

    2013-01-01

    Full Text Available Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction.

  10. Compound

    Indian Academy of Sciences (India)

    UV-vis spectra showing solvent effects on compounds (6). Figure S4. UV-vis spectra showing solvent effects on compounds (9). Figure S5. UV-vis spectra showing solvent ___, acidic--- and basic -□- effects on compound (8) in CH2Cl2 solution. Table S1. 1H and 13C NMR spectral data of salicylaldimine Schiff bases (5-8).

  11. Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study.

    Science.gov (United States)

    Siasos, Gerasimos; Oikonomou, Evangelos; Chrysohoou, Christina; Tousoulis, Dimitris; Panagiotakos, Demosthenes; Zaromitidou, Marina; Zisimos, Konstantinos; Kokkou, Eleni; Marinos, Georgios; Papavassiliou, Athanasios G; Pitsavos, Christos; Stefanadis, Christodoulos

    2013-04-01

    The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria. The analysis was conducted on 142 elderly subjects (aged 66-91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as 'low' ( 450 ml/day). From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a 'low', 48% a 'moderate' and 13% a 'high' daily coffee consumption. There was a linear increase in FMD according to coffee consumption ('low': 4.33 ± 2.51% vs 'moderate': 5.39 ± 3.09% vs 'high': 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035). Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.

  12. Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women.

    Science.gov (United States)

    Cunha, Ana Rosa; D'El-Rei, Jenifer; Medeiros, Fernanda; Umbelino, Bianca; Oigman, Wille; Touyz, Rhian M; Neves, Mario F

    2017-01-01

    Epidemiological studies demonstrate an inverse association between serum magnesium and incidence of cardiovascular disease. Diuretics commonly cause hypomagneseamia. We evaluated effects of magnesium supplementation on blood pressure (BP) and vascular function in thiazide-treated hypertensive women in a randomized, double-blind, clinical trial. Hypertensive women (40-65 years) on hydrochlorothiazide and mean 24-h BP at least 130/80 mmHg were divided into placebo and supplementation (magnesium chelate 600 mg/day) groups. Patients were evaluated for nutritional and biochemical parameters, office and ambulatory blood pressure monitoring, brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, assessment of carotid intima-media thickness, central hemodynamic parameters and pulse wave velocity at inclusion and after 6-month follow-up. The magnesium group had a significant reduction in SBP (144 ± 17 vs. 134 ± 14 mmHg, P = 0.036) and DBP (88 ± 9 vs. 81 ± 8 mmHg, P = 0.005) at 6 months, without effect on plasma glucose, lipids, or arterial stiffness parameters. The placebo group showed a significant increase in carotid intima-media thickness (0.78 ± 0.13 vs. 0.89 ± 0.14 mm, P = 0.033) without change in the magnesium group (0.79 ± 0.16 vs. 0.79 ± 0.19 mm, P = 0.716) after 6 months. The magnesium group demonstrated a significant increase in variation of FMD vs. the placebo group (+3.7 ± 2.1 vs. 2.4 ± 1.2%, P = 0.015). There was a significant correlation between the intracellular magnesium variation and FMD (r = 0.44, P = 0.011). Magnesium supplementation was associated with better BP control, improved endothelial function and amelioration of subclinical atherosclerosis in these thiazide-treated hypertensive women.

  13. Metformin improves endothelial function and carotid intima media thickness in patients with PCOS.

    Science.gov (United States)

    Kaya, Mehmet Gungor; Yildirim, Sumeyra; Calapkorur, Bekir; Akpek, Mahmut; Unluhizarci, Kursad; Kelestimur, Fahrettin

    2015-05-01

    Oral contraceptive pills (OCP) are widely used for treating women with polycystic ovary syndrome (PCOS). Metformin has beneficial effects on insulin resistance and endothelial functions. The aim of this study was to investigate the effects of treatment with drospirenone/ethinyl estradiol (EE) alone or in combination with metformin on the flow-mediated vasodilatation (FMD) and carotid intima media thickness (CIMT) in women with PCOS. Fifty women with PCOS (mean age 23 ± 5) were randomized to oral treatment of OCP alone (n = 25) or an OCP combination with metformin (n = 25) for 6 months. FMD from the brachial artery and CIMT were calculated. The hormonal profile, HOMA-IR score, basal insulin and glucose levels were studied in both groups. Before and after 6 months' treatment, echocardiographic measurements and laboratory tests were also obtained. After 6 months' treatment we observed a small decrease in FMD in the OCP group (14.9 ± 9.4 versus 14.4 ± 9.9, p = 0.801) and a slight increase in the combination group (14.5 ± 9.1 versus 15.0 ± 8.0, p = 0.715) but neither of them reached significance. CIMT increased in the OCP group (0.048 ± 0.011 to 0.050 ± 0.010 cm, p = 0.433) and decreased slightly in the combination group (0.049 ± 0.012, 0.048 ± 0.011 cm, p = 0.833). We demonstrated that adding metformin to OCP treatment may have beneficial effect on FMD and CIMT that represent vascular function in patients with PCOS. These results suggest that adding metformin to OCP treatment for PCOS could preserve the cardiovascular system and improve it.

  14. Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

    2015-05-27

    Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

  15. Blueberries Improve Endothelial Function, but Not Blood Pressure, in Adults with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    April J. Stull

    2015-05-01

    Full Text Available Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21. They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI, was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024. Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus −0.33 ± 0.14; p = 0.0023. In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased endothelial function over six weeks in subjects with metabolic syndrome.

  16. Cardiac rehabilitation improves coronary endothelial function in patients with heart failure due to dilated cardiomyopathy: A positron emission tomography study.

    Science.gov (United States)

    Legallois, Damien; Belin, Annette; Nesterov, Sergey V; Milliez, Paul; Parienti, J-J; Knuuti, Juhani; Abbas, Ahmed; Tirel, Olivier; Agostini, Denis; Manrique, Alain

    2016-01-01

    Endothelial dysfunction is common in patients with heart failure and is associated with poor clinical outcome. Cardiac rehabilitation is able to enhance peripheral endothelial function but its impact on coronary vasomotion remains unknown. We aimed to evaluate the effect of cardiac rehabilitation on coronary vasomotion in patients with heart failure. We prospectively enrolled 29 clinically stable heart failure patients from non-ischaemic dilated cardiomyopathy and without coronary risk factors. Myocardial blood flow was quantified using (15)-O water positron emission tomography at rest and during a cold pressor test, before and after 12 weeks of cardiac rehabilitation and optimization of medical therapy. Rest myocardial blood flow was significantly improved after the completion of rehabilitation compared to baseline (1.31 ± 0.38 mL/min/g vs. 1.16 ± 0.41 mL/min/g, p = 0.04). The endothelium-related change in myocardial blood flow from rest to cold pressor test and the percentage of myocardial blood flow increase during the cold pressor test were both significantly improved after cardiac rehabilitation (respectively from -0.03 ± 0.22 mL/min/g to 0.19 ± 0.22 mL/min/g, p cardiac rehabilitation significantly improves coronary vasomotion. © The European Society of Cardiology 2014.

  17. Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition

    Directory of Open Access Journals (Sweden)

    Ruangvejvorachai Preecha

    2010-10-01

    Full Text Available Abstract Background Curcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction. Methods Diabetes (DM was induced in rats by streptozotocin (STZ. Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII were examined by hydroethidine and immunofluorescence, respectively. Results The dilatory response to acetylcholine (ACh significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O2●- production. O2●- production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished. Conclusion Therefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.

  18. Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

  19. Acyloxy nitroso compounds inhibit LIF signaling in endothelial cells and cardiac myocytes: evidence that STAT3 signaling is redox-sensitive.

    Directory of Open Access Journals (Sweden)

    Carlos Zgheib

    Full Text Available We previously showed that oxidative stress inhibits leukemia inhibitory factor (LIF signaling by targeting JAK1, and the catalytic domains of JAK 1 and 2 have a cysteine-based redox switch. Thus, we postulated that the NO sibling and thiophylic compound, nitroxyl (HNO, would inhibit LIF-induced JAK-STAT3 activation. Pretreatment of human microvascular endothelial cells (HMEC-1 or neonatal rat cardiomyocytes with the HNO donors Angeli's salt or nitrosocyclohexyl acetate (NCA inhibited LIF-induced STAT3 activation. NCA pretreatment also blocked the induction of downstream inflammatory genes (e.g. intercellular adhesion molecule 1, CCAAT/enhancer binding protein delta. The related 1-nitrosocyclohexyl pivalate (NCP; not a nitroxyl donor was equally effective in inhibiting STAT3 activation, suggesting that these compounds act as thiolate targeting electrophiles. The JAK1 redox switch is likely not a target of acyloxy nitroso compounds, as NCA had no effect on JAK1 catalytic activity and only modestly affected JAK1-induced phosphorylation of the LIF receptor. However, pretreatment of recombinant human STAT3 with NCA or NCP reduced labeling of free sulfhydryl residues. We show that NCP in the presence of diamide enhanced STAT3 glutathionylation and dimerization in adult mouse cardiac myocytes and altered STAT3 under non-reducing conditions. Finally, we show that monomeric STAT3 levels are decreased in the Gαq model of heart failure in a redox-sensitive manner. Altogether, our evidence indicates that STAT3 has redox-sensitive cysteines that regulate its activation and are targeted by HNO donors and acyloxy nitroso compounds. These findings raise the possibility of new therapeutic strategies to target STAT3 signaling via a redox-dependent manner, particularly in the context of cardiac and non-cardiac diseases with prominent pro-inflammatory signaling.

  20. Fiber-rich diet with brown rice improves endothelial function in type 2 diabetes mellitus: A randomized controlled trial.

    Science.gov (United States)

    Kondo, Keiko; Morino, Katsutaro; Nishio, Yoshihiko; Ishikado, Atsushi; Arima, Hisatomi; Nakao, Keiko; Nakagawa, Fumiyuki; Nikami, Fumio; Sekine, Osamu; Nemoto, Ken-Ichi; Suwa, Makoto; Matsumoto, Motonobu; Miura, Katsuyuki; Makino, Taketoshi; Ugi, Satoshi; Maegawa, Hiroshi

    2017-01-01

    A fiber-rich diet has a cardioprotective effect, but the mechanism for this remains unclear. We hypothesized that a fiber-rich diet with brown rice improves endothelial function in patients with type 2 diabetes mellitus. Twenty-eight patients with type 2 diabetes mellitus at a single general hospital in Japan were randomly assigned to a brown rice (n = 14) or white rice (n = 14) diet and were followed for 8 weeks. The primary outcome was changes in endothelial function determined from flow debt repayment by reactive hyperemia using strain-gauge plethysmography in the fasting state. Secondary outcomes were changes in HbA1c, postprandial glucose excursions, and markers of oxidative stress and inflammation. The area under the curve for glucose after ingesting 250 kcal of assigned rice was compared between baseline (T0) and at the end of the intervention (T1) to estimate glucose excursions in each group. Improvement in endothelial function, assessed by fasting flow debt repayment (20.4% vs. -5.8%, p = 0.004), was significantly greater in the brown rice diet group than the white rice diet group, although the between-group difference in change of fiber intake was small (5.6 g/day vs. -1.2 g/day, pdiet group compared with the white rice diet group (0.01 μg/L vs. -0.04 μg/L, p = 0.063). The area under the curve for glucose was subtly but consistently lower in the brown rice diet group (T0: 21.4 mmol/L*h vs. 24.0 mmol/L*h, p = 0.043, T1: 20.4 mmol/L*h vs. 23.3 mmol/L*h, p = 0.046) without changes in HbA1c. Intervention with a fiber-rich diet with brown rice effectively improved endothelial function, without changes in HbA1c levels, possibly through reducing glucose excursions.

  1. Microfluidic Single Cell Analysis Show Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation

    Science.gov (United States)

    Gu, Mingxia; Nguyen, Patricia K.; Lee, Andrew S.; Xu, Dan; Hu, Shijun; Plews, Jordan R; Han, Leng; Huber, Bruno C.; Lee, Won Hee; Gong, Yongquan; de Almeida, Patricia E.; Lyons, Jennifer; Ikeno, Fumi; Pacharinsak, Cholawat; Connolly, Andrew J.; Gambhir, Sanjiv S.; Robbins, Robert C.; Longaker, Michael T.; Wu, Joseph C.

    2012-01-01

    Rationale Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large animal iPSC models. Objective To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia. Methods and Results Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction (MI). Compared to control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2±1.3% vs. 22.3±1.1%; P<0.001) and magnetic resonance imaging (ejection fraction at week 4: 45.8±1.3% vs. 42.3±0.9%; P<0.05). Quantitative protein assays and microfluidic single cell PCR profiling showed that piPSC-ECs released pro-angiogenic and anti-apoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery. Conclusion In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function following MI via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the

  2. Improvement of endothelial function after switching previously treated HIV-infected patients to an NRTI-sparing bitherapy with maraviroc

    Directory of Open Access Journals (Sweden)

    Enrique Bernal

    2014-11-01

    Full Text Available Introduction: Nucleoside reverse transcriptase inhibitor (NRTI is associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC is an antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted, a mediator of chronic inflammation and endothelial function. Our aim was to evaluate the maintenance of viral suppression and improvement of endothelial function in virologically suppressed HIV-infected patients switched to an NRTI-sparing combined antiretroviral therapy (cART with MVC. Materials and Methods: This observational, non-interventional, multicenter study was performed at the Infectious Diseases Service of Santa Lucia, Morales Meseguer, Virgen de la Arrixaca and Reina Sofía University Hospital (Murcia, Spain. The selection criteria were to be asymptomatic on a regimen with undetectable viral load (<50 HIV-RNA copies/mL for at least six months, no previous treatment with R5 antagonists, no evidence of previous protease inhibitor (PI failure and available R5 tropism test. Twenty-one HIV-infected patients were selected after the treatment regimen was changed to Maraviroc 150 mg/once daily plus ritonavir-boosted PI therapy. Endothelial function was prospectively evaluated through flow-mediated dilatation (FMD of the brachial artery at baseline and at weeks 24. Results: We included 21 patients on treatment with PI in combination with 2 NRTI. The mean cART exposition was 133±68.9 months. Fourteen (66.6% were males, aged 49±9 years, 15 (71.4% smokers, 4 (19.04% family history of coronary heart disease, 1 (5.76% type 2 diabetes and 3 (14.28% hypertensive, mean total cholesterol was 185.5±35 mg/dL, c-LDL 100.2±37 mg/dL, tryglicerides 170.42±92.03 mg/dL, cHDL 52.6±15.5 mg/dL, CD4 779,5±383.28 cells/mL, nadir CD4 187,96±96 cells/mL. After 24 weeks of follow-up of a switch to an NRTI-sparing regimen, 95.2% of HIV-patients on viral suppressive cART maintained

  3. Argan (Argania spinosa) oil lowers blood pressure and improves endothelial dysfunction in spontaneously hypertensive rats.

    Science.gov (United States)

    Berrougui, Hicham; Alvarez de Sotomayor, Maria; Pérez-Guerrero, Concepción; Ettaib, Abdelkader; Hmamouchi, Mohamed; Marhuenda, Elisa; Herrera, Maria Dolores

    2004-12-01

    Traditionally hand-pressed argan oil, obtained from Argania spinosa seeds, is eaten raw in south-west Morocco; its rich composition of tocopherols, MUFA and PUFA make a study of its actions on risk factors for CVD, such as hypertension, interesting. The effects of 7 weeks of treatment with argan oil (10 ml/kg) on the blood pressure and endothelial function of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were investigated. Systolic blood pressure and heart rate were measured every week by the tail-cuff method and endothelial function was assessed by carbachol (10(-8) to 10(-4) M)-induced relaxations of aortic rings and small mesenteric arteries pre-contracted with phenylephrine. Argan-oil administration reduced the mean blood pressure of SHR after the fifth week of treatment (P<0.05) and increased (P<0.01) the endothelial responses of arteries from SHR. The NO synthase inhibitor, L-N-omega-nitroarginine (3 x 10(-5) M) revealed a greater participation of NO in the relaxant effect after the treatment. When cyclooxygenase (COX) was blocked with indomethacin (10(-5) M), an involvement of COX products in the endothelium-dependent response was characterized. Enzyme immunoassay of thromboxane B2 showed a significant decrease (P<0.05) in the release of thromboxane A2 in both aorta and small mesenteric artery after argan-oil treatment of SHR. Experiments in the presence of the thromboxane A2-prostaglandin H2 receptor antagonist ICI 192,605 (10(-5) M) confirmed this result. Results after incubation with the antioxidants superoxide dismutase and catalase suggested that a decreased oxidative stress might contribute to explain the beneficial effects of argan-oil treatment.

  4. Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Rossing, P; Gall, M A

    1997-01-01

    in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually...... escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60...

  5. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells

    OpenAIRE

    Krieg, Carsten; Létourneau, Sven; Pantaleo, Giuseppe; Boyman, Onur

    2010-01-01

    IL-2 immunotherapy is an attractive treatment option for certain metastatic cancers. However, administration of IL-2 to patients can lead, by ill-defined mechanisms, to toxic adverse effects including severe pulmonary edema. Here, we show that IL-2–induced pulmonary edema is caused by direct interaction of IL-2 with functional IL-2 receptors (IL-2R) on lung endothelial cells in vivo. Treatment of mice with high-dose IL-2 led to efficient expansion of effector immune cells expressing high leve...

  6. Hepatocyte growth factor improves direct reprogramming of fibroblasts towards endothelial progenitor cells via ETV2 transduction

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-09-01

    Full Text Available Human fibroblasts can be differentiated into endothelial progenitor cells by direct reprogramming via ETV-2 transfection. Previously, we have shown that the efficacy of direct reprogramming can be enhanced by hypoxia treatment. In this study, we aim to investigate whether the efficacy of direct reprogramming of fibroblasts into EPCs via Ets variant gene 2 (ETV2 transfection can be increased with hepatocyte growth factor (HGF treatment. Foreskin-derived fibroblasts were cultured in standard medium (DMEM/F12 supplemented with fetal bovine serum. They were then transduced with a viral vector expressing ETV2 in culture medium supplemented with HGF. The transduced fibroblasts were cultured in endothelial cell medium supplemented with HGF for 28 days. The efficacy of direct reprogramming was evaluated based on expression of CD31 and VEGFR2 markers by transduced cells. Phenotypic and functional characterization of induced EPCs were also confirmed by expression of particular genes and in vitro angiogenesis assays. Our results showed that HGF significantly increased the efficacy of direct reprogramming of fibroblasts towards EPCs via ETV2 transcription factors; efficiency increased from 5.41+/-1.51% for ETV2 transduction alone to 12.31+/-2.15% for ETV2 transduction combined with HGF treatment. These findings suggest the rationale for combined use of ETV2 and HGF in direct in vitro reprogramming of fibroblasts into EPCs. [Biomed Res Ther 2016; 3(9.000: 836-843

  7. Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function.

    Science.gov (United States)

    Sakai, Takaaki; Sato, Bunpei; Hara, Koji; Hara, Yuichi; Naritomi, Yuji; Koyanagi, Samon; Hara, Hiroshi; Nagao, Tetsuhiko; Ishibashi, Toru

    2014-01-01

    The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental ROS, especially the hydroxyl radical. To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, H2, can be a useful modulator of blood vessel function. The efficacy of water containing a high concentration of H2 was tested by measuring flow-mediated dilation (FMD) of the brachial artery (BA). The subjects were randomly divided into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2 (3.5 mg H2 in 500 mL water); and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high-H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline. FMD increased in the high-H2 group (eight males; eight females) from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation) and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo group (ten males; eight females). The ratio to the baseline in the changes of FMD showed significant improvement (Phydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.

  8. Improving the electrical properties of carbon nanotubes with interhalogen compounds.

    Science.gov (United States)

    Janas, Dawid; Milowska, Karolina Z; Bristowe, Paul D; Koziol, Krzysztof K K

    2017-03-02

    The electronic properties of carbon nanostructures such as carbon nanotubes (CNTs) or graphene can easily be tuned by the action of various doping agents. We present an experimental study and numerical analysis of how and why metallic and semiconductive CNTs can be p-doped by exposing them to two interhalogens: iodine monochloride and iodine monobromide. Simple application of these compounds was found to reduce the electrical resistance by as much as 2/3 without causing any unfavorable chemical modification, which could disrupt the highly conductive network of sp(2) carbon atoms. To gain better insight into the underlying mechanism of the observed experimental results, we provide a first principles indication of how interhalogens interact with model metallic (5,5) and semiconductive (10,0) CNTs.

  9. Development and characterization of a spheroidal coculture model of endothelial cells and fibroblasts for improving angiogenesis in tissue engineering

    DEFF Research Database (Denmark)

    Wenger, Andreas; Kowalewski, Nadja; Stahl, Andreas

    2005-01-01

    Neovascularization is a critical step in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of central tissues. We have developed a three-dimensional spheroidal coculture system consisting of human umbilical vein...... endothelial cells (HUVECs) and human primary fibroblasts (hFBs) to improve angiogenesis in tissue engineering applications. Morphological analysis of cryosections from HUVEC/hFB cospheroids revealed a characteristic temporal and spatial organization with HUVECs located in the center of the cospheroid...... to the formation of heterogenic cell contacts between HUVECs and hFBs within the cospheroid. The model system introduced in this study is suitable for the development of a preformed lumenized capillary-like network ex vivo and may therefore be useful for improving angiogenesis in in vivo tissue engineering...

  10. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension

    DEFF Research Database (Denmark)

    Christiansen, Buris; Bellostas Muguerza, Natalia; Petersen, Atheline Major

    2010-01-01

    antioxidative potential, for a 4 week period or to continue their ordinary diet and act as controls. Blood pressure, endothelial function measured by flow mediated dilation (FMD) and blood samples were obtained from the participants every other week and the content of glucosinolates was measured before...... and after the study. Measurements were blinded to treatment allocation. RESULTS: In the interventional group overall FMD increased from 4% to 5.8% in the interventional group whereas in the control group FMD was stable (4% at baseline and 3.9% at the end of the study). The change in FMD...... in the interventional group was mainly due to a marked change in FMD in two participants while the other participants did not have marked changes in FMD. The observed differences were not statistically significant. Likewise significant changes in blood pressure or blood samples were not detected between or within...

  11. Cellular Metabolomics Revealed the Cytoprotection of Amentoflavone, a Natural Compound, in Lipopolysaccharide-Induced Injury of Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Weifeng Yao

    2016-09-01

    Full Text Available Amentoflavone is one of the important bioactive flavonoids in the ethylacetate extract of “Cebaiye”, which is a blood cooling and hematostatic herb in traditional Chinese medicine. The previous work in our group has demonstrated that the ethylacetate extract of Cebaiye has a notable antagonistic effect on the injury induced by lipopolysaccharide (LPS to human umbilical vein endothelial cells (HUVECs. The present investigation was designed to assess the effects and possible mechanism of cytoprotection of amentoflavone via metabolomics. Ultra-performance liquid chromatography/quadrupole time of flight-mass spectrometry (UPLC/QTOF-MS coupled with multivariate data analysis was used to characterize the variations in the metabolites of HUVECs in response to exposure to LPS and amentoflavone treatment. Seven putative metabolites (glycine, argininosuccinic acid, putrescine, ornithine, spermidine, 5-oxoproline and dihydrouracil were discovered in cells incubated with LPS and/or amentoflavone. Functional pathway analysis uncovered that the changes of these metabolites related to various significant metabolic pathways (glutathione metabolism, arginine and proline metabolism, β-alanine metabolism and glycine, serine and threonine metabolism, which may explain the potential cytoprotection function of amentoflavone. These findings also demonstrate that cellular metabolomics through UPLC/QTOF-MS is a powerful tool for detecting variations in a range of intracellular compounds upon toxin and/or drug exposure.

  12. Ethinylestradiol30μg-drospirenone and metformin: could this combination improve endothelial dysfunction in polycystic ovary syndrome?

    Directory of Open Access Journals (Sweden)

    Ilie Ioana

    2012-06-01

    Full Text Available Abstract Background We are hereby investigating for the first time the effect of the association ethinylestradiol30μg-drospirenone 3mg (DRP/EE30μg plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP levels in polycystic ovary syndrome (PCOS. Methods 25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI: 28.44 ± 6.23 who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30μg (21 days/month and metformin (1700 mg daily were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI > 25 kg/m2 were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention. Results The combination between DRP/EE30μg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48 ± 1.00 vs FMD-PCOS6 months7.43 ± 1.04, p = 0.033, as well as body composition and insulin insensitivity (p 6months – PCOSbasal difference. Conclusion A 6-month course of metformin- DRP/EE30μg (associated with weight loss improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors (ClinicalTrials.gov Identifier: NCT01459445.

  13. Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk.

    Science.gov (United States)

    Casanova, Marcela A; Medeiros, Fernanda; Trindade, Michelle; Cohen, Célia; Oigman, Wille; Neves, Mario Fritsch

    2017-01-01

    Association between hypertriglyceridemia and cardiovascular (CV) disease is still controversial. The purpose of this study was to compare omega-3 and ciprofibrate effects on the vascular structure and function in low and high CV risk hypertensive patients with hypertriglyceridemia. Twenty-nine adults with triglycerides 150-499 mg/dL were divided into low (omega-3 fatty acids 1800 mg/d or ciprofibrate 100 mg/d for 12 weeks. Treatment was switched after 8-week washout. Clinical evaluation and vascular tests were assessed at baseline and after intervention. Peripheral (131 ± 3 to 125 ± 3 mm Hg, P omega-3. In conclusion, omega-3 improved arterial stiffness and endothelial function, pointing out the beneficial effect of this therapy on vascular aging, in high-risk patients. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  14. Injectable shear-thinning hydrogels used to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium.

    Science.gov (United States)

    Gaffey, Ann C; Chen, Minna H; Venkataraman, Chantel M; Trubelja, Alen; Rodell, Christopher B; Dinh, Patrick V; Hung, George; MacArthur, John W; Soopan, Renganaden V; Burdick, Jason A; Atluri, Pavan

    2015-11-01

    The clinical translation of cell-based therapies for ischemic heart disease has been limited because of low cell retention (myocardium. To address these issues, we developed an injectable hyaluronic acid (HA) shear-thinning hydrogel (STG) and endothelial progenitor cell (EPC) construct (STG-EPC). The STG assembles as a result of interactions of adamantine- and β-cyclodextrin-modified HA. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial border zone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. Endothelial progenitor cells (DiLDL(+) VEGFR2(+) CD34(+)) were harvested from adult male rats, cultured, and suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. The STG-EPC constructs were injected at the border zone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the enhanced green fluorescent proteins from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (phosphate buffered saline injection); intramyocardial injection of EPCs alone; injection of the STG alone; and treatment with the STG-EPC construct. Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. Endothelial progenitor cells demonstrated viability within the STG. A marked increase in EPC engraftment was observed 1-week postinjection within the treated myocardium with gel delivery, compared with EPC injection alone (17.2 ± 0.8 cells per high power field (HPF) vs 3.5 cells ± 1.3 cells per HPF, P = .0002). A

  15. [Recombinant AAV1 mediated vascular endothelial growth factor gene expression promotes angiogenesis and improves neural function: experiment with rats].

    Science.gov (United States)

    Li, Shi-fang; Meng, Qing-hai; Yao, Wei-cheng; Hu, Guo-jie; Li, Gui-lin; Li, Zhao-jian; Wei, Jun-ji; Bo, Yong-li; Zhang, Zi-heng; Wang, Ren-zhi

    2009-01-20

    To investigate the therapeutic effect of vascular endothelial growth factor (VEGF) gene expression mediated by recombinant AAV1 (rAAV1) vector in brain ischemia and the mechanism thereof. Sixty-four SD rats were randomly divided into 2 equal groups and received intra-ventricular injection with rAAV1-VEGF or rAAV1-lacZ as controls. 21 days later the rats underwent transient middle cerebral artery occlusion (MCAO). Neurological severity score (NSS) was recorded 1, 2, 3, 7, 14, and 21 days after MCAO. 48 rats were sacrificed 21 days after MCAO and brains were taken out from 48 rats. Immune quantitative analysis was used to identify the quantity of VEGF expression. Immunohistochemistry was used to identify the site of VEGF expression. Immunofluorescence double labeling of von Willebrand factor (vWF) and 5-bromodeoxy-uridine (BrdU) was performed to detect the proliferation of endothelial cells. Fluorescein isothiocyanate (FITC)-dextran was infused into the caudal vein of 8 rats from each group and then the rats were killed with their brains taken out to evaluate the cerebral microvessel perfusion and microvessel density. The NSSs of the VEGF group 7, 14, and 21 days after MCAO were all significantly lower than those of the control group (all P < 0.05), and the VEGF165 protein expression quantity was 27 times as that of the control group (P < 0.05). Immunohistochemistry demonstrated that VEGF expression was distributed mainly in the caudate putamen, corpus callosum, choroid plexus, and hippocampus in the VEGF group, while no expression was detected in the control group. The microvessel density of the VEGF group was 157 +/- 13, significantly higher than that of the control group [(89 +/- 9), P < 0.05]. BrdU +/vWF + endothelial cells were detected in the area adjacent to the MCAO. The density of microvessel infused with FITC-dextran was (152,617 +/- 13,076) microm2/mm2 in the VEGF group, significantly higher than that of the control group [(91,658 +/- 6577) microm2/mm2 P

  16. Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function

    Directory of Open Access Journals (Sweden)

    Sakai T

    2014-10-01

    Full Text Available Takaaki Sakai,1 Bunpei Sato,2 Koji Hara,3 Yuichi Hara,3 Yuji Naritomi,3 Samon Koyanagi,1 Hiroshi Hara,3 Tetsuhiko Nagao,4 Toru Ishibashi51Department of Cardiology, Haradoi Hospital, Fukuoka, Japan; 2MiZ Company Limited, Fujisawa, Kanagawa, Japan; 3Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan; 4Midorino Clinic, Aoba, Higashi-ku, Fukuoka, Japan; 5Department of Rheumatology and Orthopedic Surgery, Haradoi Hospital, Fukuoka, Japan Background: The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS, H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2 neutralizes detrimental ROS, especially the hydroxyl radical. Objectives: To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, H2, can be a useful modulator of blood vessel function. Methods: The efficacy of water containing a high concentration of H2 was tested by measuring flow-mediated dilation (FMD of the brachial artery (BA. The subjects were randomly divided into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2 (3.5 mg H2 in 500 mL water; and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high-H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline. Results: FMD increased in the high-H2 group (eight males; eight females from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo

  17. Rosuvastatin improves endothelial function in patients with inflammatory joint diseases, longitudinal associations with atherosclerosis and arteriosclerosis: results from the RORA-AS statin intervention study.

    Science.gov (United States)

    Ikdahl, Eirik; Hisdal, Jonny; Rollefstad, Silvia; Olsen, Inge C; Kvien, Tore K; Pedersen, Terje R; Semb, Anne Grete

    2015-10-08

    Endothelial dysfunction is an early step in the atherosclerotic process and can be quantified by flow-mediated vasodilation (FMD). Our aim was to investigate the effect of long-term rosuvastatin therapy on endothelial function in patients with inflammatory joint diseases (IJD) with established atherosclerosis. Furthermore, to evaluate correlations between change in FMD (ΔFMD) and change in carotid plaque (CP) height, arterial stiffness [aortic pulse wave velocity (aPWV) and augmentation index (AIx)], lipids, disease activity and inflammation. Eighty-five statin-naïve patients with IJD and ultrasound-verified CP (rheumatoid arthritis: n = 53, ankylosing spondylitis: n = 24, psoriatic arthritis: n = 8) received rosuvastatin treatment for 18 months. Paired-samples t tests were used to assess ΔFMD from baseline to study end. Linear regression models were applied to evaluate correlations between ∆FMD and cardiovascular risk factors, rheumatic disease variables and medication. The mean ± SD FMD was significantly improved from 7.10 ± 3.14 % at baseline to 8.70 ± 2.98 % at study end (p < 0.001). Improvement in AIx (p < 0.05) and CP height reduction (p = 0.001) were significantly associated with ΔFMD (dependent variable). Long-term lipid lowering with rosuvastatin improved endothelial function in IJD patients with established atherosclerotic disease. Reduced arterial stiffness and CP regression were longitudinally correlated with the improvement in endothelial function measured by FMD. ClinicalTrials.gov NCT01389388 . Registered 16 April 2010.

  18. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Rinder, Christiane; Beige, Joachim

    2004-01-01

    Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure.......Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure....

  19. Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Nguyen Patricia K

    2010-09-01

    Full Text Available Abstract Background Obstructive sleep apnea (OSA has been associated with cardiovascular disease (CVD, but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP. Results Of the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR, brachial flow mediated dilation (FMD and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02 and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03 after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin. Conclusions Patients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.

  20. Middle-Term Dietary Supplementation with Red Yeast Rice Plus Coenzyme Q10 Improves Lipid Pattern, Endothelial Reactivity and Arterial Stiffness in Moderately Hypercholesterolemic Subjects.

    Science.gov (United States)

    Cicero, Arrigo F G; Morbini, Martino; Rosticci, Martina; D''Addato, Sergio; Grandi, Elisa; Borghi, Claudio

    2016-01-01

    The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness. This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device. During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment. The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects. © 2016 S. Karger AG, Basel.

  1. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

    Directory of Open Access Journals (Sweden)

    Ji Hyun Kim

    Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

  2. Improvement of endothelial progenitor outgrowth cell (EPOC)-mediated vascularization in gelatin-based hydrogels through pore size manipulation.

    Science.gov (United States)

    Fu, Jiayin; Wiraja, Christian; Muhammad, Hamizan B; Xu, Chenjie; Wang, Dong-An

    2017-08-01

    In addition to chemical compositions, physical properties of scaffolds, such as pore size, can also influence vascularization within the scaffolds. A larger pore has been shown to improve host vascular tissue invasion into scaffolds. However, the influence of pore sizes on vascularization by endothelial cells directly encapsulated in hydrogels remains unknown. In this study, micro-cavitary hydrogels with different pore sizes were created in gelatin-methacrylate hydrogels with dissolvable gelatin microspheres (MS) varying in sizes. The effect of pore sizes on vascular network formation by endothelial progenitor outgrowth cells (EPOCs) encapsulated in hydrogels was then investigated both in vitro and in vivo. When cultured in vitro, vascular networks were formed around pore structures in micro-cavitary hydrogels. The middle pore size supported best differentiation of EPOCs and thus best hydrogel vascularization in vitro. When implantation in vivo, functional connections between encapsulated EPOCs and host vasculature micro-cavitary hydrogels were established. Vascularization in vivo was promoted best in hydrogels with the large pore size due to the increased vascular tissue invasion. These results highlight the difference between in vitro and in vivo culture conditions and indicate that pore sizes shall be designed for in vitro and in vivo hydrogel vascularization respectively. Pore sizes for hydrogel vascularization in vitro shall be middle ones and pore sizes for hydrogel vascularization in vivo shall be large ones. This study reveals that the optimal pore size for hydrogel vascularization in vitro and in vivo is different. The middle pore size supported best differentiation of EPOCs and thus best hydrogel vascularization in vitro, while vascularization in vivo was promoted best in hydrogels with the large pore size due to the increased vascular tissue invasion. These results highlight the difference between in vitro and in vivo culture conditions and indicate that

  3. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    Directory of Open Access Journals (Sweden)

    Beatriz C S Boa

    reactivity was similar between groups, suggesting that only endothelial damage had occurred. Our results indicate that an aerobic routine and/or dietary modification may cause significant improvements to high fat fed animals, diminishing visceral depots, increasing eNOS expression and reducing microcirculatory dysfunction.

  4. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    Science.gov (United States)

    Boa, Beatriz C S; Souza, Maria das Graças C; Leite, Richard D; da Silva, Simone V; Barja-Fidalgo, Thereza Christina; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

    2014-01-01

    -independent microvascular reactivity was similar between groups, suggesting that only endothelial damage had occurred. Our results indicate that an aerobic routine and/or dietary modification may cause significant improvements to high fat fed animals, diminishing visceral depots, increasing eNOS expression and reducing microcirculatory dysfunction.

  5. Induction of Haemeoxygenase-1 Directly Improves Endothelial Function in Isolated Aortas from Obese Rats through the Ampk-Pi3k/Akt-Enos Pathway

    Directory of Open Access Journals (Sweden)

    Fang Han

    2015-07-01

    Full Text Available Background: Induction of haemeoxygenase-1 (HO-1 increases adiponectin secretion by remodeling adipose tissue in obesity. The objective of our study is to explore whether HO-1 induction directly improves endothelial function independent of adiponectin changes in obese rats. Methods: Rats were divided into control and obesity groups. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV. Vascular segments of the obese rats were incubated in an organ bath in the presence or absence of cobalt protoporphyrin (CoPP or CoPP plus stannous protoporphyrin. Nitric oxide (NO production, superoxide anion production and NF-κB p65 expression in the aorta were determined. The expression of AMP-activated kinase (AMPK, Akt and endothelial nitric oxide synthase (eNOS in endothelial cells was determined by western blotting. The aortic rings from the obese rats were then incubated with CoPP in the presence of specific inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K or eNOS. Results: Acetylcholine-induced EDV was significantly attenuated in the obese rats, compared with the NC group (p p in vitro in the presence of inhibitors of AMPK, PI3K or eNOS. HO-1 induction with CoPP significantly increased the activation of the AMPK-PI3K/Akt-eNOS pathway and NO production in parallel with reduced superoxide anion production and NF-κB p65 expression in obese rats. Conclusions: HO-1 induction with CoPP directly improved endothelial function in obese rats independent of adiponectin changes. The mechanism of this protective effect is related to increasing NO production by activation of the AMPK-PI3K/Akt-eNOS signaling pathway.

  6. A fish-based diet intervention improves endothelial function in postmenopausal women with type 2 diabetes mellitus: a randomized crossover trial.

    Science.gov (United States)

    Kondo, Keiko; Morino, Katsutaro; Nishio, Yoshihiko; Kondo, Motoyuki; Nakao, Keiko; Nakagawa, Fumiyuki; Ishikado, Atsushi; Sekine, Osamu; Yoshizaki, Takeshi; Kashiwagi, Atsunori; Ugi, Satoshi; Maegawa, Hiroshi

    2014-07-01

    The beneficial effects of fish and n-3 polyunsaturated fatty acids (PUFAs) consumption on atherosclerosis have been reported in numerous epidemiological studies. However, to the best of our knowledge, the effects of a fish-based diet intervention on endothelial function have not been investigated. Therefore, we studied these effects in postmenopausal women with type 2 diabetes mellitus (T2DM). Twenty-three postmenopausal women with T2DM were assigned to two four-week periods of either a fish-based diet (n-3 PUFAs ≧ 3.0 g/day) or a control diet in a randomized crossover design. Endothelial function was measured with reactive hyperemia using strain-gauge plethysmography and compared with the serum levels of fatty acids and their metabolites. Endothelial function was determined with peak forearm blood flow (Peak), duration of reactive hyperemia (Duration) and flow debt repayment (FDR). A fish-based dietary intervention improved Peak by 63.7%, Duration by 27.9% and FDR by 70.7%, compared to the control diet. Serum n-3 PUFA levels increased after the fish-based diet period and decreased after the control diet, compared with the baseline (1.49 vs. 0.97 vs. 1.19 mmol/l, p diet intervention, possibly due to the inhibition of the activity of soluble epoxide hydrolase. A fish-based dietary intervention improves endothelial function in postmenopausal women with T2DM. Dissociation between the serum n-3 PUFA concentration and endothelial function suggests that the other factors may contribute to this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study.

    Science.gov (United States)

    Kaur, Savneet; Kumar, T R Santhosh; Uruno, Akira; Sugawara, Akira; Jayakumar, Karunakaran; Kartha, Chandrasekharan Cheranellore

    2009-11-01

    Recent studies have reported a marked impairment in the number and functions of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). In view of an important role of eNOS in angiogenesis, in the present study, we evaluated the effects of eNOS gene transfer in ex vivo expanded EPCs isolated from patients with CAD. The expanded EPCs were transfected with mammalian expression vector pcDNA3.1-eNOS containing the full-length human eNOS gene using lipofectamine. About 35-40% of the eNOS-EPCs had higher expression of eNOS as compared to untransfected EPCs. EPCs transfected with pcDNA3.0-EGFP, the plasmid vector expressing green fluorescent protein (GFP) were used as control. The untransfected, GFP-transfected and eNOS-transfected EPCs were compared in terms of important functional attributes of angiogenesis such as proliferation, migration, differentiation and adhesion/integration into tube-like structures in vitro. Functional studies revealed that in the presence of defined growth conditions, compared to the untransfected and GFP-transfected cells, eNOS-EPCs from patients with CAD have a significant increase in [3H] thymidine-labeled DNA (P < 0.01), migration (14.6 +/- 1.8 and 16.5 +/- 1.9 vs. 23.5 +/- 3.4 cells/field, P < 0.01), ability to differentiate into endothelial-like spindle-shaped cells (46 +/- 4.5 and 56.5 +/- 2.1 vs. 93.2 +/- 6.6 cells/field, P < 0.001) and also incorporation into tube-like structures on the matrigel (GFP-EPCs: 21.25 +/- 2.9 vs. GFP-eNOS-EPCs: 34.5 +/- 5.5 cells/field, P < 0.05). We conclude that eNOS gene transfection is a valuable approach to augment angiogenic properties of ex vivo expanded EPCs and eNOS-modified EPCs may offer significant advantages than EPCs alone in terms of their clinical use in patients with myocardial ischemia.

  8. CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function.

    Science.gov (United States)

    Tiyerili, Vedat; Zimmer, Sebastian; Jung, Suzin; Wassmann, Kerstin; Naehle, Claas P; Lütjohann, Dieter; Zimmer, Andreas; Nickenig, Georg; Wassmann, Sven

    2010-07-01

    Inhibition of the cannabinoid receptor CB(1) (CB(1)-R) exerts numerous positive cardiovascular effects such as modulation of blood pressure, insulin sensitivity and serum lipid concentrations. However, direct vascular effects of CB(1)-R inhibition remain unclear. CB(1)-R expression was validated in vascular smooth muscle cells (VSMCs) and aortic tissue of mice. Apolipoprotein E-deficient (ApoE-/-) mice were treated with cholesterol-rich diet and the selective CB(1)-R antagonist rimonabant or vehicle for 7 weeks. CB(1)-R inhibition had no effect on atherosclerotic plaque development, collagen content and macrophage infiltration but led to improved aortic endothelium-dependent vasodilation and decreased aortic reactive oxygen species (ROS) production and NADPH oxidase activity. Treatment of cultured VSMC with rimonabant resulted in reduced angiotensin II-mediated but not basal ROS production and NADPH oxidase activity. CB(1)-R inhibition with rimonabant and AM251 led to down-regulation of angiotensin II type 1 receptor (AT1-R) expression, whereas stimulation with the CB(1)-R agonist CP 55,940 resulted in AT1-R up-regulation, indicating that AT1-R expression is directly regulated by the CB(1)-R. CB(2)-R inhibition had no impact on AT1-R expression in VSMC. Consistently, CB(1)-R inhibition decreased aortic AT1-R expression in vivo. CB(1)-R inhibition leads to decreased vascular AT1-R expression, NADPH oxidase activity and ROS production in vitro and in vivo. This antioxidative effect is associated with improved endothelial function in ApoE-/- mice, indicating beneficial direct vascular effects of CB(1)-R inhibition.

  9. Age related vascular endothelial function following lifelong sedentariness: positive impact of cardiovascular conditioning without further improvement following low frequency high intensity interval training

    OpenAIRE

    Grace, Fergal M.; Herbert, Peter; Ratcliffe, John W.; New, Karl J.; Baker, Julien S.; Sculthorpe, Nicholas F.

    2015-01-01

    Abstract Aging is associated with diffuse impairments in vascular endothelial function and traditional aerobic exercise is known to ameliorate these changes. High intensity interval training (HIIT) is effective at improving vascular function in aging men with existing disease, but its effectiveness remains to be demonstrated in otherwise healthy sedentary aging. However, the frequency of commonly used HIIT protocols may be poorly tolerated in older cohorts. Therefore, the present study invest...

  10. Genistein inhibits TNF-α-induced endothelial inflammation through the protein kinase pathway A and improves vascular inflammation in C57BL/6 mice

    OpenAIRE

    Jia, Zhenquan; Babu, Pon Velayutham Anandh; Si, Hongwei; Nallasamy, Palanisamy; Zhu, Hong; Zhen, Wei; Misra, Hara P.; Li, Yunbo; Liu, Dongmin

    2013-01-01

    Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1 µM–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. Genistein also significantly suppressed TNF-α-induced production of adhesion molecules and chemokines such...

  11. Inferring Association between Compound and Pathway with an Improved Ensemble Learning Method.

    Science.gov (United States)

    Song, Meiyue; Jiang, Zhenran

    2015-11-01

    Emergence of compound molecular data coupled to pathway information offers the possibility of using machine learning methods for compound-pathway associations' inference. To provide insights into the global relationship between compounds and their affected pathways, a improved Rotation Forest ensemble learning method called RGRF (Relief & GBSSL - Rotation Forest) was proposed to predict their potential associations. The main characteristic of the RGRF lies in using the Relief algorithm for feature extraction and regarding the Graph-Based Semi-Supervised Learning method as classifier. By incorporating the chemical structure information, drug mode of action information and genomic space information, our method can achieve a better precision and flexibility on compound-pathway prediction. Moreover, several new compound-pathway associations that having the potential for further clinical investigation have been identified by database searching. In the end, a prediction tool was developed using RGRF algorithm, which can predict the interactions between pathways and all of the compounds in cMap database. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.

    Science.gov (United States)

    Shafiee, Abbas; Patel, Jatin; Wong, Ho Yi; Donovan, Prudence; Hutmacher, Dietmar W; Fisk, Nicholas M; Khosrotehrani, Kiarash

    2017-02-01

    The prospect of using endothelial progenitors is currently hampered by their low engraftment upon transplantation. We report that mesenchymal stem/stromal cells (MSCs), independent of source and age, improve the engraftment of endothelial colony forming cells (ECFCs). MSC coculture altered ECFC appearance to an elongated mesenchymal morphology with reduced proliferation. ECFC primed via MSC contact had reduced self-renewal potential, but improved capacity to form tube structures in vitro and engraftment in vivo Primed ECFCs displayed major differences in transcriptome compared to ECFCs never exposed to MSCs, affecting genes involved in the cell cycle, up-regulating of genes influencing mesenchymal transition, adhesion, extracellular matrix. Inhibition of NOTCH signaling, a potential upstream regulator of mesenchymal transition, in large part modulated this gene expression pattern and functionally reversed the mesenchymal morphology of ECFCs. The collective results showed that primed ECFCs survive better and undergo a mesenchymal transition that is dependent on NOTCH signaling, resulting in significantly increased vasculogenic potential.-Shafiee, A., Patel, J., Wong, H. Y., Donovan, P., Hutmacher, D. W., Fisk, N. M., Khosrotehrani, K. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling. © FASEB.

  13. Grape-derived polyphenols improve aging-related endothelial dysfunction in rat mesenteric artery: role of oxidative stress and the angiotensin system.

    Directory of Open Access Journals (Sweden)

    Noureddine Idris Khodja

    Full Text Available Aging is characterized by the development of an endothelial dysfunction, which affects both the nitric oxide (NO- and the endothelium-derived hyperpolarizing factor (EDHF-mediated relaxations, associated with vascular oxidative stress and the activation of the angiotensin system. This study investigated whether red wine polyphenols (RWPs, antioxidants and potent stimulators of NO- and EDHF-mediated relaxations improve aging-related endothelial dysfunction, and, if so, examined the underlying mechanism. Mesenteric artery reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX staining, and expression of target proteins by immunohistochemical staining. Control young rats (16 weeks received solvent (ethanol, 3% v/v, and middle-aged rats (46 weeks either solvent or RWPs (100 mg/kg/day in the drinking water. The acetylcholine-induced endothelium-dependent NO component was slightly reduced whereas the EDHF component was markedly blunted in rings of middle-aged rats compared to young rats. The endothelial dysfunction was associated with oxidative stress, an upregulation of angiotensin II and AT1 receptors and a down-regulation of SK(Ca, IK(Ca, and angiotensin converting enzyme. Intake of RWPs for either one or two weeks improved the NO and the EDHF components of the relaxation, and normalized oxidative stress, the expression of SK(Ca, IK(Ca and the components of the angiotensin system. The protective effect of the 2-week RWPs treatment persisted for one and two weeks following stopping intake of RWPs. Thus, intake of RWPs caused a persistent improvement of the endothelial function, particularly the EDHF component, in middle-aged rats and this effect seems to involve the normalization of the expression of SK(Ca, IK(Ca and the angiotensin system.

  14. Grape-derived polyphenols improve aging-related endothelial dysfunction in rat mesenteric artery: role of oxidative stress and the angiotensin system.

    Science.gov (United States)

    Idris Khodja, Noureddine; Chataigneau, Thierry; Auger, Cyril; Schini-Kerth, Valérie B

    2012-01-01

    Aging is characterized by the development of an endothelial dysfunction, which affects both the nitric oxide (NO)- and the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations, associated with vascular oxidative stress and the activation of the angiotensin system. This study investigated whether red wine polyphenols (RWPs), antioxidants and potent stimulators of NO- and EDHF-mediated relaxations improve aging-related endothelial dysfunction, and, if so, examined the underlying mechanism. Mesenteric artery reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX staining, and expression of target proteins by immunohistochemical staining. Control young rats (16 weeks) received solvent (ethanol, 3% v/v), and middle-aged rats (46 weeks) either solvent or RWPs (100 mg/kg/day) in the drinking water. The acetylcholine-induced endothelium-dependent NO component was slightly reduced whereas the EDHF component was markedly blunted in rings of middle-aged rats compared to young rats. The endothelial dysfunction was associated with oxidative stress, an upregulation of angiotensin II and AT1 receptors and a down-regulation of SK(Ca), IK(Ca), and angiotensin converting enzyme. Intake of RWPs for either one or two weeks improved the NO and the EDHF components of the relaxation, and normalized oxidative stress, the expression of SK(Ca), IK(Ca) and the components of the angiotensin system. The protective effect of the 2-week RWPs treatment persisted for one and two weeks following stopping intake of RWPs. Thus, intake of RWPs caused a persistent improvement of the endothelial function, particularly the EDHF component, in middle-aged rats and this effect seems to involve the normalization of the expression of SK(Ca), IK(Ca) and the angiotensin system.

  15. Compound faults detection of rotating machinery using improved adaptive redundant lifting multiwavelet

    Science.gov (United States)

    Chen, Jinglong; Zi, Yanyang; He, Zhengjia; Yuan, Jing

    2013-07-01

    Due to the character of diversity and complexity, the compound faults detection of rotating machinery under non-stationary operation turns into a challenging task. Multiwavelet with two or more base functions and many excellent properties provides a possibility to detect and extract all the features of compound faults at one time. However, the fixed basis functions independent of the vibration signal may decrease the accuracy of fault detection. Moreover, the decomposition result of discrete multiwavelet transform does not possess time invariance, which is harmful to extract the feature of periodical impulses. To overcome these deficiencies, based on the Hermite splines interpolation, taking the minimum envelope spectrum entropy as the optimization objective, adaptive redundant lifting multiwavelet is developed. Additionally, in order to eliminate error propagation of decomposition results, adaptive redundant lifting multiwavelet is improved by adding the normalization factors. As an effective method, Hilbert transform demodulation analysis is used to extract the fault feature from the high frequency modulation signal. The proposed method incorporating improved adaptive redundant lifting multiwavelet (IARLM) with Hilbert transform demodulation analysis is applied to compound faults detection for the simulation experiment, rolling element bearing test bench and traveling unit of electric locomotive. Compared with some other fault detection methods, the results show the superior effectiveness and reliability on the compound faults detection.

  16. Chronic inhibition of lipoprotein-associated phospholipase A2 does not improve coronary endothelial function: A prospective, randomized-controlled trial.

    Science.gov (United States)

    Prasad, Megha; Lennon, Ryan; Barsness, Gregory W; Prasad, Abhiram; Gulati, Rajiv; Lerman, Lilach O; Lerman, Amir

    2018-02-15

    Lipoprotein-associated phospholipase A2 (Lp-PLA2), a novel biomarker for vascular inflammation, is associated with coronary endothelial dysfunction (CED) and independently predicts cardiovascular events. The current study aimed to determine whether darapladib, an orally administered Lp-PLA2 inhibitor, improved CED. Fifty-four patients with CED were enrolled in a double-blinded randomized placebo-controlled trial, and were randomized to receive oral darapladib, 160mg daily, or placebo. Coronary angiography and invasive coronary endothelial function assessment were performed at baseline and post-6months of treatment. Primary endpoints were change in coronary artery diameter and coronary blood flow in response to acetylcholine. Additionally, Lp-PLA2 activity was measured at baseline and on follow-up to evaluate for adherence and drug effect. Fifty-four patients were randomized to placebo (n=29) and darapladib (n=25). Mean age in darapladib group was 55.2.±11.7years vs. 54.0±10.5years (p=0.11). On follow-up, there was no significant difference in the percent response to acetylcholine of coronary artery diameter in treatment vs. placebo group (+3 (IQR -9, 15) vs. +3 (-12, 19); p=0.87) or coronary blood flow (-5 (IQR -24, 54) vs. 39 (IQR -26, 67); p=0.41). There was significant reduction in Lp-PLA2 activity in the treatment arm vs. placebo (-76 (IQR -113, -52) vs. -7(-21, -7); p<0.001). Lp-PLA2 inhibition with darapladib did not improve coronary endothelial function, despite significantly reduced Lp-PLA2 activity with darapladib. This study suggests endogenous Lp-PLA2 may not play a primary role in coronary endothelial function in humans. CLINICALTRIALS. NCT01067339. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

    Science.gov (United States)

    Clarenbach, Christian F; Sievi, Noriane A; Brock, Matthias; Schneiter, Didier; Weder, Walter; Kohler, Malcolm

    2015-08-01

    Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Preliminary studies have shown that both airflow obstruction and systemic inflammation may contribute to endothelial dysfunction in COPD. Lung volume reduction surgery (LVRS) is a treatment option in selected patients with COPD with emphysema that improves breathing mechanics and lung function. To determine the effect of LVRS on endothelial function and systemic inflammation. We conducted a randomized controlled trial in 30 patients scheduled for LVRS. In the intervention group, immediate LVRS was performed after baseline evaluation followed by reassessment 3 months later. In the control group, reassessment followed 3 months after baseline evaluation, and thereafter LVRS was performed. The primary outcome measures were the treatment effect on endothelial function and systemic inflammation. In the LVRS group 14 patients completed the trial and 13 in the control group. LVRS led to a relative reduction in mean (SD) residual volume/total lung capacity of -12% (12%) and an increase in FEV1 of 29% (27%). Flow-mediated dilatation of the brachial artery increased in the intervention group as compared with the control group (+2.9%; 95% confidence interval, +2.1 to +3.6%; P < 0.001), whereas there was no significant change in systemic inflammation. A significant treatment effect on mean blood pressure was observed (-9.0 mm Hg; 95% confidence interval, -17.5 to -0.5; P = 0.039). Endothelial function and blood pressure are improved 3 months after LVRS in patients with severe COPD and emphysema. LVRS may therefore have beneficial effects on cardiovascular outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 01020344).

  18. High doses of vascular endothelial growth factor 165 safely, but transiently, improve myocardial perfusion in no-option ischemic disease.

    Science.gov (United States)

    Giusti, Imarilde I; Rodrigues, Clarissa G; Salles, Felipe B; Sant'Anna, Roberto T; Eibel, Bruna; Han, Sang W; Ludwig, Eduardo; Grossman, Gabriel; Prates, Paulo Roberto L; Sant'Anna, João Ricardo M; Filho, Guaracy F Teixeira; Markoski, Melissa M; Nesralla, Ivo A; Nardi, Nance B; Kalil, Renato A K

    2013-10-01

    Gene therapy can induce angiogenesis in ischemic tissues. The aim of this study was to assess safety, feasibility, and results, both clinical and on myocardial perfusion, of gene therapy in refractory angina. This was a phase I/II, prospective, temporal-controlled series, clinical trial. Thirteen patients were maintained for minimum 6 months under optimized clinical management, and then received intramyocardial injections of 2000 μg plasmid vascular endothelial growth factor 165 and were followed by single-photon emission computed tomography (SPECT), treadmill tests, Minnesota quality of life questionnaire (QOL), and New York Heart Association (NYHA) functional plus Canadian Cardiovascular Society (CCS) angina classifications. There were no deaths, early or late. During the optimized clinical treatment, we observed worsening of rest ischemia scores on SPECT (p<0.05). After treatment, there was a transitory increase in myocardial perfusion at the third-month SPECT under stress (pre-operative [pre-op] 18.38 ± 7.51 vs. 3 months 15.31 ± 7.30; p<0.01) and at the sixth month under rest (pre-op 13.23 ± 7.98 vs. 6 months: 16.92 ± 7.27; p<0.01). One year after, there were improvements in treadmill test steps (pre-op 2.46 ± 2.07 vs.12 months 4.15 ± 2.23; p<0.01) and oxygen consumption (pre-op 7.66 ± 4.47 vs.12 months 10.89 ± 4.65; p<0.05), QOL (pre-op 48.23 ± 18.35 vs.12 months 28.31 ± 18.14; p<0.01) scores, and CCS (pre-op 3 [3-3.5] vs.12 months 2 [1-2.5]; p<0.01) and NYHA (pre-op 3 [3-3] vs. 2 [2-2] vs. 12 months 2 [1-2]; p<0.01) classes. Gene therapy demonstrated to be feasible and safe in this advanced ischemic cardiomyopathy patient sample. There were improvements in clinical evaluation parameters, and a transitory increase in myocardial perfusion detectable by SPECT scintigraphy. NCT00744315 http://clinicaltrials.gov/

  19. Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

    NARCIS (Netherlands)

    Longo, M; Jain, [No Value; Langenveld, J; Vedernikov, YP; Garfield, RE; Hankins, GDV; Anderson, GD; Saade, GR

    2004-01-01

    Objective: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these

  20. A new approach to improve the specificity of flow-mediated dilation for indicating endothelial function in cardiovascular research

    NARCIS (Netherlands)

    Atkinson, G.; Batterham, A.M.; Thijssen, D.H.J.; Green, D.J.

    2013-01-01

    Flow-mediated dilation (FMD) is a noninvasive indicator of endothelial function and is routinely expressed as the percentage change in arterial diameter (FMD%) from a resting baseline (Dbase) to a postischemic peak (Dpeak). This expression is equivalent to the ratio of Dpeak/Dbase and is, therefore,

  1. SAINT-liposome-polycation particles, a new carrier for improved delivery of siRNAs to inflamed endothelial cells

    NARCIS (Netherlands)

    Kowalski, Piotr S.; Kuninty, Praneeth R.; Bijlsma, Klaas T.; Stuart, Marc C. A.; Leus, Niek G. J.; Ruiters, Marcel H. J.; Molema, Grietje; Kamps, Jan A. A. M.

    Interference with acute and chronic inflammatory processes by means of delivery of siRNAs into microvascular endothelial cells at a site of inflammation demands specific, non-toxic and effective siRNA delivery system. In the current work we describe the design and characterization of siRNA carriers

  2. Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals - a randomized cross-over trial.

    Science.gov (United States)

    Miyoshi, Toru; Noda, Yoko; Ohno, Yuko; Sugiyama, Hiroki; Oe, Hiroki; Nakamura, Kazufumi; Kohno, Kunihisa; Ito, Hiroshi

    2014-10-01

    Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. Healthy volunteers [10] were given supplementation at 4g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4h=-0.5±1.2 vs. -2.0±1.6%, P=0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2-4h, and returned to baseline at 8h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve=220±209 vs. 374±216mg/h/dL, P=0.04) and remnant lipoprotein-cholesterol (incremental area under the curve=21.7±13.8 vs. 13.3±12.9mg/h/dL, P=0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4h after the cookie test. Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Regular consumption of vitamin D-fortified yogurt drink (Doogh improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Shab-Bidar Sakineh

    2011-11-01

    Full Text Available Abstract Background Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D. In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated. Methods Subjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50 or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50 twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP-9 were evaluated at the beginning and after the 12-week intervention period. Results The intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI, glycated hemoglobin (HbA1c, triacylglycerols, high-density lipoprotein cholesterol (HDL-C, endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P P = 0.009 and P = 0.005, respectively but disappeared for E-selectin (P = 0.092. On the contrary, after controlling for serum 25(OHD, the differences disappeared for endothelin-1(P = 0.066 and MMP-9 (P = 0.277 but still remained significant for E-selectin (P = 0.011. Conclusions Ameliorated vitamin D status was accompanied by improved glycemic status, lipid profile and endothelial biomarkers in T2D subjects. Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers. Trial registration

  4. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial.

    Science.gov (United States)

    Shab-Bidar, Sakineh; Neyestani, Tirang R; Djazayery, Abolghassem; Eshraghian, Mohammad-Reza; Houshiarrad, Anahita; Gharavi, A'azam; Kalayi, Ali; Shariatzadeh, Nastaran; Zahedirad, Malihe; Khalaji, Niloufar; Haidari, Homa

    2011-11-24

    Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D). In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated. Subjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50) or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50) twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM) and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP)-9 were evaluated at the beginning and after the 12-week intervention period. The intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI), glycated hemoglobin (HbA1c), triacylglycerols, high-density lipoprotein cholesterol (HDL-C), endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P < 0.05, for all). Interestingly, difference in changes of endothelin-1, E-selectin and MMP-9 concentrations in FYD compared to PYD (-0.35 ± 0.63 versus -0.03 ± 0.55, P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P < 0.05 for all), even after controlling for changes of QUICKI, FM and waist circumference, remained significant for endothelin-1 and MMP-9 (P = 0.009 and P = 0.005, respectively) but disappeared for E-selectin (P = 0.092). On the contrary, after controlling for serum 25(OH)D, the differences disappeared for endothelin-1(P = 0.066) and MMP-9 (P = 0.277) but still remained significant for E-selectin (P = 0

  5. Improved contrast for high frame rate imaging using coherent compounding combined with spatial matched filtering.

    Science.gov (United States)

    Lou, Yang; Yen, Jesse T

    2017-07-01

    The concept of high frame rate ultrasound imaging (typically greater than 1000 frames per second) has inspired new fields of clinical applications for ultrasound imaging such as fast cardiovascular imaging, fast Doppler imaging and real-time 3D imaging. Coherent plane-wave compounding is a promising beamforming technique to achieve high frame rate imaging. By combining echoes from plane waves with different angles, dynamic transmit focusing is efficiently accomplished at all points in the image field. Meanwhile, the image frame rate can still be kept at a high level. Spatial matched filtering (SMF) with plane-wave insonification is a novel ultrafast beamforming method. An analytical study shows that SMF is equivalent to synthetic aperture methods that can provide dynamic transmit-receive focusing throughout the field of view. Experimental results show that plane-wave SMF has better performance than dynamic-receive focusing. In this paper, we propose integrating coherent plane-wave compounding with SMF to obtain greater image contrast. By using a combination of SMF beamformed images, image contrast is improved without degrading its high frame rate capabilities. The performance of compounded SMF (CSMF) is evaluated and compared with that of synthetic aperture focusing technique (SAFT) beamforming and compounded dynamic-receive-focus (CDRF) beamforming. The image quality of different beamforming methods was quantified in terms of contrast-to-noise ratio (CNR). Our results show that the new SMF based plane-wave compounding method provides better contrast than DAS based compounding method. Also CSMF can obtain a similar contrast level to dynamic transmit-receive focusing with only 21 transmit events. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Layer-by-layer assembly to modify poly(l-lactic acid) surface toward improving its cytocompatibility to human endothelial cells.

    Science.gov (United States)

    Zhu, Yabin; Gao, Changyou; He, Tao; Liu, Xingyu; Shen, Jiacong

    2003-01-01

    A novel technique to introduce free amino groups onto polyester scaffolds via aminolyzing the ester groups with diamine has been developed recently. Positively charged chitosan was then deposited onto the aminolyzed poly(l-lactic acid) (PLLA) membrane surface in a layer-by-layer assembly manner using poly(styrene sulfonate, sodium salt) (PSS) as a negatively charged polyelectrolyte. The layer-by-layer deposition process of PSS and chitosan was monitored by UV-vis absorbance spectroscopy, energy transfer by fluorescence spectroscopy, and advancing contact angle measurements. The existed chitosan obviously improved the cytocompatibility of PLLA to human endothelial cells. The cell attachment, activity, and proliferation on the PLLA membranes assembled with three or five bilayers of PSS/chitosan with chitosan as the outermost layer were better than those with one bilayer of PSS/chitosan or the control PLLA. The cells also showed morphology of an elongated shape with abundant cytoplasm, and a confluent cell layer was reached after being cultured for 4 days. Measurement of von Willebrand factor secreted by these endothelial cells (ECs) verified the endothelial function. Hence, better ECs compatible PLLA were produced.

  7. Genistein inhibits TNF-α-induced endothelial inflammation through the protein kinase pathway A and improves vascular inflammation in C57BL/6 mice.

    Science.gov (United States)

    Jia, Zhenquan; Babu, Pon Velayutham Anandh; Si, Hongwei; Nallasamy, Palanisamy; Zhu, Hong; Zhen, Wei; Misra, Hara P; Li, Yunbo; Liu, Dongmin

    2013-10-03

    Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1 μM-5 μM) significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis. Genistein also significantly suppressed TNF-α-induced production of adhesion molecules and chemokines such as sICAM-1, sVCAM-1, sE-Selectin, MCP-1 and IL-8, which play key role in the firm adhesion of monocytes to activated endothelial cells (ECs). Genistein at physiologically relevant concentrations didn't significantly induce antioxidant enzyme activities or scavenge free radicals. Further, blocking the estrogen receptors (ERs) in ECs didn't alter the preventive effect of genistein on endothelial inflammation. However, inhibition of protein kinase A (PKA) significantly attenuated the inhibitory effects of genistein on TNF-α-induced monocyte adhesion to ECs as well as the production of MCP-1 and IL-8. In animal study, dietary genistein significantly suppressed TNF-α-induced increase in circulating chemokines and adhesion molecules in C57BL/6 mice. Genistein treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, genistein protects against TNF-α-induced vascular endothelial inflammation both in vitro and in vivo models. This anti-inflammatory effect of genistein is independent of the ER-mediated signaling machinery or antioxidant activity, but mediated via the PKA signaling pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Nanoliposomal carriers for improvement the bioavailability of high - valued phenolic compounds of pistachio green hull extract.

    Science.gov (United States)

    Rafiee, Zahra; Barzegar, Mohsen; Sahari, Mohammad Ali; Maherani, Behnoush

    2017-04-01

    In present study, nanoliposomes were prepared by thin hydration method with different concentrations of phenolic compounds (500, 750 and 1000ppm) of pure extract and lecithin (1, 2 and 3%w/w) and characterized by considering the particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE) and morphology. The results showed that nanoliposome (90.39-103.78nm) had negative surface charge varied from -51.5±0.9 to -40.2±0.2mV with a narrow size distribution (PDI≈0.069-0.123). Nanoliposomes composed of 1% lecithin with 1000ppm of phenolic compounds had the highest EE (52.93%). The FTIR analysis indicated the formation of hydrogen bonds between the polar zone of phospholipid and the OH groups of phenolic compounds. Phenolic compounds also increased phase transition temperature (Tc) of nanoliposomes (2.01-7.24°C). Moreover, nanoliposomes had considerable stability during storage. Consequently, liposome is an efficient carrier for protection and improving PGHE biofunctional actives in foodstuffs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Rask-Madsen, C; Ihlemann, N; Krarup, T

    2001-01-01

    Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n......, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease....... after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high...

  10. Evaluation of Endothelial Dysfunction In Vivo.

    Science.gov (United States)

    Todiras, Mihail; Alenina, Natalia; Bader, Michael

    2017-01-01

    Vascular endothelial cells play a major role in maintaining cardiovascular homeostasis. Impairment of physiological properties of the endothelium, such as the promotion of vasodilation and anti-aggregation, leads to a condition called endothelial dysfunction. Endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis and has been shown to have prognostic value in predicting vascular events including stroke and myocardial infarction.Endothelial-dependent vasodilation is one of the most widely used methods for assessment of endothelial function in rodents. It includes pharmacological stimulation (for example by acetylcholine) of endothelial release of NO and other vasoactive compounds in comparison with vascular response to endothelium-independent dilators such as sodium nitroprusside. However, usually this technique is performed in anesthetized animals. Here we describe a method which allows evaluation of endothelial dysfunction in conscious, freely moving mice and rats.

  11. Compound 21 prevents endothelial inflammation and leukocyte adhesion in vitro and in vivo

    DEFF Research Database (Denmark)

    Sampson, Amanda K; Irvine, Jennifer C; Shihata, Waled A

    2016-01-01

    BACKGROUND: The angiotensin AT2 (AT2R) is upregulated in disease states such as atherosclerosis; with blockade of the AT2R shown to exacerbate plaque formation. Direct stimulation of the AT2R has been shown to be anti-atherogenic but the mechanisms and pathways involved remain unknown. PURPOSE...... TNFα and IL-6 mRNA expression in M1 macrophages. The effects of C21 on TNFα-induced endothelial activation were abolished in the presence of the AT2R antagonist PD 123319 confirming the effects of C21 are AT2R-mediated. In addition, we observed high fat diet (HFD)-induced leukocyte adhesion...

  12. Improving the review of standard operating procedures: a novel electronic system for compounding pharmacies.

    Science.gov (United States)

    Brensel, Robert; Brensel, Scott; Ng, Amy

    2013-01-01

    Since the New England Compounding Center disaster in 2012, the importance of following correct procedures during every phase of customized pharmacy has been a focus of governmental interest and action as well as public scrutiny. Many pharmacies rely on the rote review of standard operating procedures to ensure that staff members understand and follow protocols that ensure the safety and potency of all compounds prepared, but that approach to continuing education can be cumbersome and needlessly time-consuming. In addition, documenting and retrieving evidence of employee competence can be difficult. In this article, we describe our use of online technology to improve our methods of educating staff about the full range of standard operating procedures that must be followed in our pharmacy. The system we devised and implemented has proven to be effective, easy to update and maintain, very inexpensive, and user friendly. Its use has reduced the time previously required for a read-over review of standard operating procedures from 30 or 40 minutes to 5 or 10 minutes in weekly staff meetings, and we can now easily document and access proof of employees' comprehension of that content. It is our hope that other small compounding pharmacies will also find this system of online standard operating procedure review helpful.

  13. Comparison between Culture Conditions Improving Growth and Differentiation of Blood and Bone Marrow Cells Committed to the Endothelial Cell Lineage

    Directory of Open Access Journals (Sweden)

    Valgimigli Simond

    2010-01-01

    Full Text Available Abstract The aim of this study was to compare different cell sources and culture conditions to obtain endothelial progenitor cells (EPCs with predictable antigen pattern, proliferation potential and in vitro vasculogenesis. Pig mononuclear cells were isolated from blood (PBMCs and bone marrow (BMMCs. Mesenchymal stem cells (MSCs were also derived from pig bone marrow. Cells were cultured on fibronectin in the presence of a high concentration of VEGF and low IGF-1 and FGF-2 levels, or on gelatin with a lower amount of VEGF and higher IGF-1 and FGF-2 concentrations. Endothelial commitment was relieved in almost all PBMCs and BMMCs irrespective of the protocol used, whilst MSCs did not express a reliable pattern of EPC markers under these conditions. BMMCs were more prone to expand on gelatin and showed a better viability than PBMCs. Moreover, about 90% of the BMMCs pre-cultured on gelatin could adhere to a hyaluronan-based scaffold and proliferate on it up to 3 days. Pre-treatment of BMMCs on fibronectin generated well-shaped tubular structures on Matrigel, whilst BMMCs exposed to the gelatin culture condition were less prone to form vessel-like structures. MSCs formed rough tubule-like structures, irrespective of the differentiating condition used. In a relative short time, pig BMMCs could be expanded on gelatin better than PBMCs, in the presence of a low amount of VEGF. BMMCs could better specialize for capillary formation in the presence of fibronectin and an elevated concentration of VEGF, whilst pig MSCs anyway showed a limited capability to differentiate into the endothelial cell lineage.

  14. Comparison between Culture Conditions Improving Growth and Differentiation of Blood and Bone Marrow Cells Committed to the Endothelial Cell Lineage

    Directory of Open Access Journals (Sweden)

    Muscari Claudio

    2010-02-01

    Full Text Available Abstract The aim of this study was to compare different cell sources and culture conditions to obtain endothelial progenitor cells (EPCs with predictable antigen pattern, proliferation potential and in vitro vasculogenesis. Pig mononuclear cells were isolated from blood (PBMCs and bone marrow (BMMCs. Mesenchymal stem cells (MSCs were also derived from pig bone marrow. Cells were cultured on fibronectin in the presence of a high concentration of VEGF and low IGF-1 and FGF-2 levels, or on gelatin with a lower amount of VEGF and higher IGF-1 and FGF-2 concentrations. Endothelial commitment was relieved in almost all PBMCs and BMMCs irrespective of the protocol used, whilst MSCs did not express a reliable pattern of EPC markers under these conditions. BMMCs were more prone to expand on gelatin and showed a better viability than PBMCs. Moreover, about 90% of the BMMCs pre-cultured on gelatin could adhere to a hyaluronan-based scaffold and proliferate on it up to 3 days. Pre-treatment of BMMCs on fibronectin generated well-shaped tubular structures on Matrigel, whilst BMMCs exposed to the gelatin culture condition were less prone to form vessel-like structures. MSCs formed rough tubule-like structures, irrespective of the differentiating condition used. In a relative short time, pig BMMCs could be expanded on gelatin better than PBMCs, in the presence of a low amount of VEGF. BMMCs could better specialize for capillary formation in the presence of fibronectin and an elevated concentration of VEGF, whilst pig MSCs anyway showed a limited capability to differentiate into the endothelial cell lineage.

  15. Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study.

    Science.gov (United States)

    Asgary, S; Afshani, M R; Sahebkar, A; Keshvari, M; Taheri, M; Jahanian, E; Rafieian-Kopaei, M; Malekian, F; Sarrafzadegan, N

    2016-10-01

    Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (Pcholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB.

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

    Science.gov (United States)

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

    2016-04-01

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

  17. A Novel Phenolic Compound, Chloroxynil, Improves Agrobacterium-Mediated Transient Transformation in Lotus japonicus.

    Science.gov (United States)

    Kimura, Mitsuhiro; Cutler, Sean; Isobe, Sachiko

    2015-01-01

    Agrobacterium-mediated transformation is a commonly used method for plant genetic engineering. However, the limitations of Agrobacterium host-plant interactions and the complexity of plant tissue culture often make the production of transgenic plants difficult. Transformation efficiency in many legume species, including soybean and the common bean, has been reported to be quite low. To improve the transformation procedure in legumes, we screened for chemicals that increase the transformation efficiency of Lotus japonicus, a model legume species. A Chemical library was screened and chemicals that increase in transient transformation efficiency of L. japonicus accession, Miyakojima MG-20 were identified. The transient transformation efficiency was quantified by reporter activity in which an intron-containing reporter gene produces the GUS protein only when the T-DNA is expressed in the plant nuclei. We identified a phenolic compound, chloroxynil, which increased the genetic transformation of L. japonicus by Agrobacterium tumefaciens strain EHA105. Characterization of the mode of chloroxynil action indicated that it enhanced Agrobacterium-mediated transformation through the activation of the Agrobacterium vir gene expression, similar to acetosyringone, a phenolic compound known to improve Agrobacterium-mediated transformation efficiency. Transient transformation efficiency of L. japonicus with 5 μM chloroxynil was 60- and 6- fold higher than that of the control and acetosyringone treatment, respectively. In addition, transgenic L. japonicus lines were successfully generated by 5 μM chloroxynil treatment.Furthermore, we show that chloroxynil improves L. japonicus transformation by Agrobacterium strain GV3101 and rice transformation. Our results demonstrate that chloroxynil significantly improves Agrobacterium tumefaciens-mediated transformation efficiency of various agriculturally important crops.

  18. Low n-6/n-3 PUFA Ratio Improves Lipid Metabolism, Inflammation, Oxidative Stress and Endothelial Function in Rats Using Plant Oils as n-3 Fatty Acid Source.

    Science.gov (United States)

    Yang, Li Gang; Song, Zhi Xiu; Yin, Hong; Wang, Yan Yan; Shu, Guo Fang; Lu, Hui Xia; Wang, Shao Kang; Sun, Gui Ju

    2016-01-01

    Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p stress compared with the other groups (p stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.

  19. Cilostazol Improves Proangiogenesis Functions in Human Early Endothelial Progenitor Cells through the Stromal Cell-Derived Factor System and Hybrid Therapy Provides a Synergistic Effect In Vivo.

    Science.gov (United States)

    Tseng, Shih-Ya; Chao, Ting-Hsing; Li, Yi-Heng; Cho, Chung-Lung

    2016-01-01

    This study investigated the effect of cilostazol on proangiogenesis functions in human early endothelial progenitor cells (EPCs) in vitro and the therapeutic implication of hybrid therapy with cilostazol and human early EPCs in vivo. Cilostazol significantly increased colony-forming units and enhanced differentiation of EPCs toward endothelial lineage. Treatments resulted in antiapoptotic effects and stimulated proliferation and migration and in vitro vascular tube formation through activation of stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)/phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway. Blood flow recovery and capillary density in murine ischemic hindlimbs were significantly improved in cilostazol-treated, human early EPCs-treated, and cotreatment groups. The effects were attenuated with SDF-1α inhibition. Plasma SDF-1α levels were significantly higher in 3 active treatment groups after surgery, with greatest effects observed in hybrid therapy. The angiogenic effects of transplanted EPCs pretreated with cilostazol ex vivo were superior to untreated EPCs using in vivo Matrigel assay. Implanted EPCs were incorporated into the capillary, with pretreatment or cotreatment with cilostazol resulting in enhanced effects. Taken together, cilostazol promotes a large number of proangiogenic functions in human early EPCs through activation of SDF-1/CXCR4/PI3K/Akt signaling, and hybrid therapy provides a synergistic effect in vivo. Cotreatment may be beneficial in ischemic disease.

  20. Grafting of gelatin on electrospun poly(caprolactone) nanofibers to improve endothelial cell spreading and proliferation and to control cell Orientation.

    Science.gov (United States)

    Ma, Zuwei; He, Wei; Yong, Thomas; Ramakrishna, S

    2005-01-01

    We modified the surface of electrospun poly(caprolactone) (PCL) nanofibers to improve their compatibility with endothelial cells (ECs) and to show the potential application of PCL nanofibers as a blood vessel tissue-engineering scaffold. Nonwoven PCL nanofibers (PCL NF) and aligned PCL nanofibers (APCL NF) were fabricated by electrospinning technology. To graft gelatin on the nanofiber surface, PCL nanofibers were first treated with air plasma to introduce -COOH groups on the surface, followed by covalent grafting of gelatin molecules, using water-soluble carbodiimide as the coupling agent. The chemical change in the material surface during surface modification was confirmed by X-ray photoelectron spectroscopy and quantified by colorimetric methods. ECs were cultured to evaluate the cytocompatibility of surface-modified PCL NF and APCL NF. Gelatin grafting can obviously enhance EC spreading and proliferation compared with the original material. Moreover, gelatin-grafted APCL NF readily orients ECs along the fibers whereas unmodified APCL NF does not. Immunostaining micrographs showed that ECs cultured on gelatin-grafted PCL NF were able to maintain the expression of three characteristic markers: platelet-endothelial cell adhesion molecule 1 (PECAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). The surface-modified PCL nanofibrous material is a potential candidate material in blood vessel tissue engineering.

  1. Improving the Sustainability of Office Partition Manufacturing: Balancing Options for Reducing Emissions of Volatile Organic Compounds

    Directory of Open Access Journals (Sweden)

    Marc A. Rosen

    2009-06-01

    Full Text Available Options are examined to improve the sustainability of office partition manufacturing by reducing volatile organic compounds (VOC emissions. Base VOC emissions for a typical plant are estimated using a mass balance approach. Pollution prevention and sustainability measures are assessed using realistic criteria and weightings. Sustainability has been considered from an industry perspective, considering factors like economics, environmental impact, quality, health and safety. Through a case study, it is demonstrated that several advantageous options are available for reducing VOC emissions in manufacturing office furniture partitions, and thereby enhancing the sustainability of that industrial operation. The measures deemed most viable include implementing several best management practices, not painting of non-visible parts, switching gluing processes, recycling solvent and modifying attachments. The results are intended to be balanced so as to improve their acceptability and adoptability by industry. It appears that it would be advantageous for manufacturers of office panels to evaluate the feasibility of these measures and to implement the most appropriate. The results are likely extendable to other operations in the wood furniture industry, and would improve their sustainability.

  2. Design of new disulfide-based organic compounds for the improvement of self-healing materials.

    Science.gov (United States)

    Matxain, Jon M; Asua, José M; Ruipérez, Fernando

    2016-01-21

    Self-healing materials are a very promising kind of materials due to their capacity to repair themselves. Among others, diphenyl disulfide-based compounds (Ph2S2) appear to be among the best candidates to develop materials with optimum self-healing properties. However, few is known regarding both the reaction mechanism and the electronic structure that make possible such properties. In this vein, theoretical approaches are of great interest. In this work, we have carried out theoretical calculations on a wide set of different disulfide compounds, both aromatic and aliphatic, in order to elucidate the prevalent reaction mechanism and the necessary electronic conditions needed for improved self-healing properties. Two competitive mechanisms were considered, namely, the metathesis and the radical-mediated mechanism. According to our calculations, the radical-mediated mechanism is the responsible for this process. The formation of sulfenyl radicals strongly depends on the S-S bond strength, which can be modulated chemically by the use of proper derivatives. At this point, amino derivatives appear to be the most promising ones. In addition to the S-S bond strength, hydrogen bonding between disulfide chains seems to be relevant to favour the contact among disulfide units. This is crucial for the reaction to take place. The calculated hydrogen bonding energies are of the same order of magnitude as the S-S bond energies. Finally, reaction barriers have been analysed for some promising candidates. Two reaction mechanisms were compared, namely, the [2+2] metathesis reaction mechanism and the [2+1] radical-mediated mechanism. No computational evidence for the existence of any transition state for the metathesis mechanism was found, which indicates that the radical-mediated mechanism is the one responsible in the self-healing process of these materials. Interestingly, the calculated reaction barriers are around 10 kcal mol(-1) regardless the substituent employed. All these

  3. Research on six degrees of freedom compound control technology for improving photoelectric pod pointing accuracy

    Science.gov (United States)

    Zhou, Junpeng; Li, Yan; Chen, Juan; Nian, Lun; Zhang, Haibo

    2017-08-01

    High line-of-sight (LOS) pointing precision is a prerequisite for improving the laser confrontation capability of a photoelectric interference pod. In a traditional photoelectric pod, the time delay in TV tracking reduces the system phase margin, system stability and LOS pointing precision. In view of this deficiency, a normalized LMS algorithm is introduced to compensate for the TV camera delay in the inner gimbal position loop of a two-axis and four-gimbal structure, which can allow a pod to avoid system phase margin reduction. Meanwhile, a fast steering mirror (FSM) system is used to improve the LOS pointing precision. First, this paper proposes a normalized LMS algorithm. Second, a compound control structure, with an outer gimbal analog controller and an inner gimbal lag-lead controller, is designed. Finally, the FSM beam control precision is analyzed. The experimental results show that the normalized LMS algorithm yields almost no delay; moreover, the azimuth and pitch beam control accuracies are greater by a factor of 15 and 3, respectively, compared with those of a conventional photoelectric pod.

  4. Longxuetongluo capsule inhibits atherosclerosis progression in high-fat diet-induced ApoE(-/-) mice by improving endothelial dysfunction.

    Science.gov (United States)

    Zheng, Jiao; Liu, Binglin; Lun, Qixing; Gu, Xiaopan; Pan, Bo; Zhao, Yunfang; Xiao, Wei; Li, Jun; Tu, Pengfei

    2016-12-01

    Chinese dragon's blood has been used to treat blood stasis for thousands of years. Its total phenolic extract (Longxuetongluo capsule, LTC) is used for the treatment of ischemic stroke; however, its protective effect against atherosclerosis remains poorly understood. This paper aims to investigate the antiatherosclerotic effect of LTC and the underlying mechanisms in high-fat diet (HFD)-induced ApoE(-/-) mice. The levels of plasma lipid and areas of atherosclerotic lesions in the aortic sinus in ApoE(-/-) mice were evaluated. The effect of LTC on the nitric oxide (NO) production in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells (HUVECs) was determined. The adhesion of monocytes to ox-LDL-stimulated HUVECs was further studied. LTC at low, medium, and high doses markedly decreased the atherosclerotic lesion areas of the aortic sinus in HFD-induced ApoE(-/-) mice by 26.4% (p atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Orachorn Boonla

    2015-07-01

    Full Text Available In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP in a rat model of two kidney-one clip (2K-1C renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg−1 or 100 mg kg−1 or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p < 0.05. Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE, decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p < 0.05. Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity.

  6. Lifestyle factors and endothelial function.

    Science.gov (United States)

    Papageorgiou, Nikolaos; Tousoulis, Dimitris; Androulakis, Emmanuel; Giotakis, Aris; Siasos, Gerasimos; Latsios, George; Stefanadis, Christodoulos

    2012-01-01

    Atherosclerotic disease remains a major health problem around the world. The central role of endothelium and inflammation in all stages of the atherosclerotic process is advocated by significant data. Moreover, clinical evidence supports the prognostic potential of endothelial dysfunction for the development of ischemic events and for adverse outcome after acute coronary syndromes. Interestingly, suboptimal lifestyle choices are implicated in the development and deterioration of this endothelial dysfunction, a fact with significant impact, considering the contribution of endothelial dysfunction in atherosclerosis and its complications. Many epidemiological research studies, using a variety of strategies, provide encouraging evidence suggesting that lifestyle modifications may have significant impact regarding the improvement of endothelial function. However, little is known about how individual's genetic background interacts with environmental influences on vascular health, thereby making the interpretation of the relative importance of lifestyle interventions more complicated.

  7. Improvement of Bioactive Compound Classification through Integration of Orthogonal Cell-Based Biosensing Methods

    Directory of Open Access Journals (Sweden)

    Goran N. Jovanovic

    2007-01-01

    Full Text Available Lack of specificity for different classes of chemical and biological agents, and false positives and negatives, can limit the range of applications for cell-based biosensors. This study suggests that the integration of results from algal cells (Mesotaenium caldariorum and fish chromatophores (Betta splendens improves classification efficiency and detection reliability. Cells were challenged with paraquat, mercuric chloride, sodium arsenite and clonidine. The two detection systems were independently investigated for classification of the toxin set by performing discriminant analysis. The algal system correctly classified 72% of the bioactive compounds, whereas the fish chromatophore system correctly classified 68%. The combined classification efficiency was 95%. The algal sensor readout is based on fluorescence measurements of changes in the energy producing pathways of photosynthetic cells, whereas the response from fish chromatophores was quantified using optical density. Change in optical density reflects interference with the functioning of cellular signal transduction networks. Thus, algal cells and fish chromatophores respond to the challenge agents through sufficiently different mechanisms of action to be considered orthogonal.

  8. The Profile and Bioaccessibility of Phenolic Compounds in Cereals Influenced by Improved Extrusion Cooking Treatment

    Science.gov (United States)

    Zeng, Zicong; Liu, Chengmei; Luo, Shunjing; Chen, Jun; Gong, Ersheng

    2016-01-01

    The aim of this study was to investigate the effect of Improved Extrusion Cooking Treatment (IECT) on the phenolics and its bioaccessibility in cereals, represented by brown rice, wheat, and oat. Data showed that total phenolic content and total antioxidant activity in free form were significantly decreased, while the bound form was increased after IECT. After IECT, the total free phenolic acids of brown rice and wheat were significantly decreased by 5.88% and 45.66%, respectively, while the total bound phenolic acids of brown rice, wheat, and oat were significantly increased by 6.45%, 8.78%, and 9.10%, respectively. Brown rice provided the most bioaccessible phenolics and antioxidant compounds, followed by oat and wheat. IECT significantly decreased the bioaccessible phenolics of brown rice and oat by 31.09% and 30.95%, while it had minimal effect on the bioaccessible phenolics of wheat. These results showed that IECT greatly affected the phenolics and its bioaccessibiltiy of cereals, with the effect depending on cereal matrix and the sensitivity of free and bound phenolics. Furthermore, bioaccessible phenolic acids of raw and processed cereals were considerably low, and it slightly contributed to the bioaccessible phenolics. PMID:27513581

  9. Compound semiconductor field-effect transistors with improved dc and high frequency performance

    Energy Technology Data Exchange (ETDEWEB)

    Zolper, J.C.; Sherwin, M.E.; Baca, A.G.

    1995-12-31

    A method for making compound semiconductor devices including the use of a p-type dopant is disclosed wherein the dopant is co-implanted with an n-type donor species at the time the n-channel is deposited. Also disclosed are devices manufactured using the method. In the preferred embodiment n-MESFETs and other similar field effect transistor devices are manufactured using C ions implanted with Si atoms in GaAs to form an n-channel. C exhibits a unique characteristic in the context of the invention in that it exhibits a low activation efficiency (typically, 50% or less) as a p-type dopant, and consequently, it acts to sharpen the Si n-channel by compensating Si donors in the region the Si-channel tail, but does not contribute substantially to the acceptor concentration in the region of the buried p-implant. As a result, the invention provides for improved field effect transistor devices with enhancement of both DC and high-frequency performance.

  10. Ferulic Acid Improves Functional Recovery after Acute Spinal Cord Injury in Rats by Inducing Hypoxia to Inhibit microRNA-590 and Elevate Vascular Endothelial Growth Factor Expressions.

    Science.gov (United States)

    Li, Zhenjie; Wang, Shengyun; Li, Wenfang; Yuan, Hongbin

    2017-01-01

    Spinal cord injury (SCI) is the leading cause of paralysis, disability and even death in severe cases, and neural stem cells (NSCs) transplant has been employed for repairing SCI. Ferulic acid (FA) is able to promote neurogenesis in various stem cell therapies. We aimed to investigate the effect of FA on NSC transplant therapy, and the underlying mechanism, in improving functional recovery in SCI rat model. A rat model of SCI was established, which then received transplant of NSCs with or without FA pre-treatment. Functional recovery of the SCI rats was then evaluated, in terms of spinal cord water content, myeloperoxidase activity and behavioral assessments. Effect of FA in inducing hypoxia in NSCs was also assessed, followed by identifying the hypoxic regulated microRNA and the subsequent target gene. Transplant of FA pre-treated NSCs improved functional recovery of SCI rats to a more significant extent than NSCs without FA pre-treatment. The beneficial effects of FA in repairing SCI was mediated by inducing hypoxia in NSCs, which in turn inhibited microRNA-590 to elevate vascular endothelial growth factor expression. Our findings support the clinical potential of FA in improving efficacy of NSC transplant therapy for treatment of SCI.

  11. Flow analysis techniques as effective tools for the improved environmental analysis of organic compounds expressed as total indices.

    Science.gov (United States)

    Maya, Fernando; Estela, José Manuel; Cerdà, Víctor

    2010-04-15

    The scope of this work is the accomplishment of an overview about the current state-of-the-art flow analysis techniques applied to the environmental determination of organic compounds expressed as total indices. Flow analysis techniques are proposed as effective tools for the quick obtention of preliminary chemical information about the occurrence of organic compounds on the environment prior to the use of more complex, time-consuming and expensive instrumental techniques. Recently improved flow-based methodologies for the determination of chemical oxygen demand, halogenated organic compounds and phenols are presented and discussed in detail. The aim of the present work is to demonstrate the highlight of flow-based techniques as vanguard tools on the determination of organic compounds in environmental water samples. (c) 2010 Elsevier B.V. All rights reserved.

  12. FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis.

    Science.gov (United States)

    Cui, Kai; Ruan, Yajun; Wang, Tao; Rao, Ke; Chen, Zhong; Wang, Shaogang; Liu, Jihong

    2017-03-01

    ratio of smooth muscle to collagen, decreased the ratio of Bax to Bcl-2, and inhibited activity of the Smad and non-Smad pathways. FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED. Cui K, Ruan Y, Wang T, et al. FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis. J Sex Med 2017;14:323-335. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  13. AB088. FTY720 supplementation partially improves erectile dysfunction in rats with streptozotocin-induced type 1 diabetes through inhibition of endothelial dysfunction and corporal fibrosis

    Science.gov (United States)

    Cui, Kai; Ruan, Yajun; Tang, Zhe; Rao, Ke; Wang, Tao; Wang, Shaogang; Chen, Zhong; Liu, Jihong

    2017-01-01

    Background To investigate whether FTY720, approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis, could ameliorate erectile dysfunction induced by diabetes mellitus (DMED). Methods Thirty-two Sprague-Dawley rats (8 weeks old) were induced type I DM and the other eight rats formed the control (n=8). Eight weeks later, 17 rats with DMED tested with an apomorphine test were divided in two groups: DMED (n=8) and DMED + FTY720 (1 mg/kg/d; n=9). Treatment of FTY720 lasted for 4 weeks. Results Impaired erectile function, inhibited S1P3/Akt/NO/cGMP activity, serious corporal fibrosis and over-activated pathways (the Smad and non-Smad) were found in the DMED group compared with the control, while FTY720 partly but significantly improved these pathological changes induced by DM. Conclusions FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED.

  14. The functions of endothelial progenitor cells were significantly improved after treatment with intravenous immunoglobulin and aspirin in children with Kawasaki disease.

    Science.gov (United States)

    Xu, Ming Guo; Men, Li Na; Zu, Ying; Zhao, Chun Yu; Meng, Xiang Chun; Wang, Tao

    2011-04-01

    We sought to determine the effects of treatment with intravenous immunoglobulin (IVIG) and aspirin on the functions of endothelial progenitor cells (EPCs) in patients with Kawasaki disease (KD) as well as its relationship with concentrations of tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP). Ten KD patients in the acute phase of their disease were recruited. We investigated EPC functions in children with KD before and after treatment with IVIG and aspirin. In vitro assays were used to measure the functions, including proliferation, adhesion, and migration activities, of EPCs. Plasma levels of TNF-α and hs-CRP were also assessed. All of the data were assessed before and at 7 days after treatment initiation. EPC functions after 7 days of treatment with IVIG and aspirin were significantly improved than they were before treatment with IVIG and aspirin. Treatment with IVIG and aspirin significantly decreased TNF-α and hs-CRP concentrations. There was a significant linear regression relationship between decreased plasma TNF-α levels, hs-CRP levels, and increased functions of circulating EPCs. The results of our study indicate that the functions of circulating EPCs improved after treatment with IVIG and aspirin, which may be related to decreased concentrations of TNF-α and hs-CRP.

  15. Taurine Supplementation Improves Erectile Function in Rats with Streptozotocin-induced Type 1 Diabetes via Amelioration of Penile Fibrosis and Endothelial Dysfunction.

    Science.gov (United States)

    Ruan, Yajun; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weiming; Liu, Jihong; Ye, Zhangqun

    2016-05-01

    For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. To investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Type 1 diabetes mellitus was induced in male rats by using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for 4 weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for 4 weeks. Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was improved in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway-related proteins was reduced. Taurine supplementation ameliorated erectile response as well as histologic and molecular alterations. Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  16. Heart Rate reduction by IVabradine for improvement of ENDothELial function in patients with coronary artery disease: the RIVENDEL study.

    Science.gov (United States)

    Mangiacapra, Fabio; Colaiori, Iginio; Ricottini, Elisabetta; Balducci, Francesco; Creta, Antonio; Demartini, Chiara; Minotti, Giorgio; Di Sciascio, Germano

    2017-01-01

    Data from experimental studies suggest that the f current-inhibitor ivabradine may reduce oxidative stress and improve endothelial function. We aimed to evaluate the effect of ivabradine on endothelial function in patients with coronary artery disease (CAD) after complete revascularization with percutaneous coronary angioplasty (PCI). At least 30 days after PCI, 70 patients were randomized (T0) to receive ivabradine 5 mg twice daily (ivabradine group, n = 36) or to continue with standard medical therapy (control group, n = 34). After 4 weeks (T1), ivabradine dose was adjusted up to 7.5 mg twice daily in patients with heart rate (HR) at rest >60 bpm, and thereafter continued for additional 4 weeks (T2). At all timings, brachial artery reactivity was assessed by flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD). No significant differences were observed at T0 between ivabradine and control groups in terms of HR (68.0 ± 6.4 vs. 67.6 ± 6.4 bpm; p = 0.803), FMD (8.7 ± 4.9 vs. 8.0 ± 5.5 %; p = 0.577) and NMD (12.7 ± 6.7 vs. 13.3 ± 6.2 %; p = 0.715). Over the study period, a significant reduction of HR (65.2 ± 5.9 bpm at T1, 62.2 ± 5.7 bpm at T2; p < 0.001), and improvement of FMD (12.2 ± 6.2 % at T1, 15.0 ± 7.7 % at T2; p < 0.001) and NMD (16.6 ± 10.4 % at T1, 17.7 ± 10.8 at T2; p < 0.001) were observed in the ivabradine group, while no significant changes were observed in the control group. In the ivabradine group, a moderate negative correlation was observed between the HR variation and FMD variation from T1 to T3 (r = -0.448; p = 0.006). In patients with CAD undergoing complete revascularization with PCI, addition of ivabradine to the standard medical therapy produces a significant improvement in endothelial function. This effect seems to be related to HR reduction. ClinicalTrials.gov number, NCT02681978.

  17. AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats

    Science.gov (United States)

    Yang, Qin; Xue, Hong-Mei; Wong, Wing-Tak; Tian, Xiao-Yu; Huang, Yu; Tsui, Stephen KW; Ng, Patrick KS; Wohlfart, Paulus; Li, Huige; Xia, Ning; Tobias, Silke; Underwood, Malcolm John; He, Guo-Wei

    2011-01-01

    BACKGROUND AND PURPOSE Nitric oxide (NO) plays an important role in endothelial function, and impaired NO production is involved in hypertension. Therefore, compounds that regulate endothelial NO synthase (eNOS) may be of therapeutic benefit. A novel, low molecular weight compound AVE3085 is a recently developed compound with the ability to enhance eNOS transcription. The present study investigated the effects of AVE3085 in endothelial dysfunction associated with hypertension. EXPERIMENTAL APPROACH Spontaneously hypertensive rats (SHRs) were treated with AVE 3085 (10 mg·kg·day−1, orally) for 4 weeks. Isometric force measurement was performed on rings of isolated aortae in organ baths. Protein expression of eNOS, phosphorylated-eNOS and nitrotyrosine in the aortae were examined by Western blotting. mRNA for eNOS in rat aortae were examined by reverse-transcriptase polymerase chain reaction (RT-PCR). KEY RESULTS AVE3085 greatly improved endothelium-dependent relaxations in the aortae of SHRs. This functional change was accompanied by up-regulated expression of eNOS protein and mRNA, enhanced eNOS phosphorylation and decreased formation of nitrotyrosine. Furthermore, AVE3085 treatment reduced the blood pressure in SHR without affecting that of hypertensive eNOS−/− mice. CONCLUSIONS AND IMPLICATIONS The eNOS-transcription enhancer AVE3085 restored impaired endothelial function in a hypertensive model. The present study provides a solid basis for the potential development of eNOS-targeting drugs to restore down-regulated eNOS, as a new strategy in hypertension. PMID:21385179

  18. Cocoa flavanol intake improves endothelial function and Framingham Risk Score in healthy men and women: a randomised, controlled, double-masked trial: the Flaviola Health Study.

    Science.gov (United States)

    Sansone, Roberto; Rodriguez-Mateos, Ana; Heuel, Jan; Falk, David; Schuler, Dominik; Wagstaff, Rabea; Kuhnle, Gunter G C; Spencer, Jeremy P E; Schroeter, Hagen; Merx, Marc W; Kelm, Malte; Heiss, Christian

    2015-10-28

    Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-mediated vasodilation (FMD)) that plateaued after 2 weeks. Subsequently, in a randomised, controlled, double-masked, parallel-group dietary intervention trial (Clinicaltrials.gov: NCT01799005), 100 healthy, middle-aged (35-60 years) men and women consumed either the CF-containing drink (450 mg) or a nutrient-matched CF-free control bi-daily for 1 month. The primary end point was FMD. Secondary end points included plasma lipids and blood pressure, thus enabling the calculation of Framingham Risk Scores and pulse wave velocity. At 1 month, CF increased FMD over control by 1·2 % (95 % CI 1·0, 1·4 %). CF decreased systolic and diastolic blood pressure by 4·4 mmHg (95 % CI 7·9, 0·9 mmHg) and 3·9 mmHg (95 % CI 6·7, 0·9 mmHg), pulse wave velocity by 0·4 m/s (95 % CI 0·8, 0·04 m/s), total cholesterol by 0·20 mmol/l (95 % CI 0·39, 0·01 mmol/l) and LDL-cholesterol by 0·17 mmol/l (95 % CI 0·32, 0·02 mmol/l), whereas HDL-cholesterol increased by 0·10 mmol/l (95 % CI 0·04, 0·17 mmol/l). By applying the Framingham Risk Score, CF predicted a significant lowering of 10-year risk for CHD, myocardial infarction, CVD, death from CHD and CVD. In healthy individuals, regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk, demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects.

  19. Discovery of p1736, a novel antidiabetic compound that improves peripheral insulin sensitivity in mice models.

    Directory of Open Access Journals (Sweden)

    Jessy Anthony

    Full Text Available Insulin resistance is a characteristic feature of Type 2 diabetes. Insulin resistance has also been implicated in the pathogenesis of cardiovascular disease. Currently used thiazolidinedione (TZD insulin sensitizers although effective, have adverse side effects of weight gain, fluid retention and heart failure. Using fat cell-based phenotypic drug discovery approach we identified P1736, a novel antidiabetic molecule that has completed Phase II clinical trials. The present study evaluated the in vitro and in vivo pharmacological properties of P1736. P1736 is a non-TZD and it did not activate human PPAR(Peroxisome Proliferator Activated Receptor Gamma receptors. P1736 caused dose dependent increase in glucose uptake (EC50-400 nM in the insulin resistant 3T3 adipocytes. The compound (10 µM induced translocation of GLUT-4 (Glucose Transporter type 4 transporters in these adipocytes while metformin (1.0mM was inactive. In diabetic db/db mice, P1736 (150 mg/kg was more efficacious than metformin in lowering plasma glucose (35% vs 25% and triglyceride levels (38% vs 31%. P1736 tested at 5mg/kg, twice daily doses, reduced glucose by 41% and triglycerides by 32%, in db/db mice. These effects were not associated with adverse effects on body weight or liver function. Rosiglitazone (5mg/kg, twice daily caused 60% and 40 % decreases in glucose and triglyceride levels, respectively. However, rosiglitazone induced 13% weight gain (p<0.05 in db/db mice. P1736 was also efficacious in ob/ob mice wherein 30-35% decrease in glucose and significant improvement in hyperinsulinemia were observed. Administration of P1736 to ob/ob mice resulted in 70% increase in glucose uptake in soleus muscles while metformin caused 38% increase. P1736 exhibited excellent safety profile and was weight neutral in all preclinical models of diabetes. Thus, P1736 with its unique pharmacology coupled with PPAR- independent mode of action could represent an alternative option in the

  20. Vitamin E improves testicular damage in streptozocin-induced diabetic rats, via increasing vascular endothelial growth factor and poly(ADP-ribose) polymerase-1.

    Science.gov (United States)

    Omar, S S; Aly, R G; Badae, N M

    2017-11-21

    The precise mechanism by which diabetes impairs spermatogenesis and testicular function is not exactly known. Vascular endothelial growth factor (VEGF) and poly(ADP-ribose) polymerase-1 (PARP-1) are important for germ cell homeostasis and repair of DNA respectively. The aim of this study was to investigate the correlation between diabetes-induced testicular damage and testicular VEGF and PARP-1 expression and the possible protective role of vitamin E supplementation. A total of 45 male Wistar albino rats were randomly divided into three groups: Group I (nondiabetic rats), Group II (streptozocin-induced diabetic rats) and Group III (streptozocin-induced diabetic rats treated orally with 0.4 mg/kg vitamin E). Five weeks later, testicular tissue was used for assessment of MDA concentration by colorimetry, histopathological examination and immunostaining for PARP-1 and VEGFIn diabetic rats, testicular weight, seminiferous tubule diameter and germinal epithelial thickness were decreased, basement membrane was thickened and Johnsen score decreased. Reduced VEGF and PARP-1 immunostaining were associated with decreased Johnsen score in diabetic rats. Vitamin E administration was protective against oxidative stress-associated damage evidenced by lower MDA levels, improved testicular weight, spermatogenesis and higher immunostaining for VEGF and PARP-1. Testicular VEGF and PARP-1 might therefore be helpful biomarkers for diabetic testicular damage. Administration of vitamin E may have a protective role against diabetes-induced testicular damage. © 2017 Blackwell Verlag GmbH.

  1. Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial

    National Research Council Canada - National Science Library

    Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

    2015-01-01

    Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans...

  2. Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds

    NARCIS (Netherlands)

    Mateo Anson, N.; Selinheimo, E.; Havenaar, R.; Aura, A.-M.; Mattila, I.; Lehtinen, P.; Bast, A.; Poutanen, K.; Haenen, G.R.M.M.

    2009-01-01

    Ferulic acid (FA) is the most abundant phenolic compound in wheat grain, mainly located in the bran. However, its bioaccessibility from the bran matrix is extremely low. Different bioprocessing techniques involving fermentation or enzymatic and fermentation treatments of wheat bran were developed

  3. Improvement of on-line solid-phase extraction for determining phenolic compounds in water

    Energy Technology Data Exchange (ETDEWEB)

    Pocurull, E. [Univ. Rovira i Virgili, Tarragona (Spain). Dept. de Quimica; Marce, R.M. [Univ. Rovira i Virgili, Tarragona (Spain). Dept. de Quimica; Borrull, F. [Univ. Rovira i Virgili, Tarragona (Spain). Dept. de Quimica

    1995-11-01

    Modifying the most common design for the on-line coupling of a precolumn to reversed phase LC with diode array detection has resulted in reduction of the broadening of the peaks which results when the compounds of interest are strongly retained by a highly hydrophobic sorbent. The modification consists of the desorption of the analytes trapped on the precolumn solely by the organic solvent used to modify the solvent strength of the mobile phase. Results obtained using this design were compared with those obtained with the conventional design, with C{sub 18} and PLRP-S precolumns. The performance of the system was also tested with a highly cross-linked styrene-divinylbenzene copolymer (ENVI-chrom P) precolumn for the determination of phenolic compounds in real samples. The advantages and disadvantages are discussed. Ion-pair solid phase extraction is used in order to increase the breakthrough volumes of more polar compounds, mainly phenol. The use of the new design enables phenolic compounds to be determined at the low {mu}g L{sup -1} level with limits of detection ranging between 0.1 and 2 {mu}g L{sup -1} in tap water when a 10 mL sample was analyzed. (orig.)

  4. Maternal melatonin administration mitigates coronary stiffness and endothelial dysfunction, and improves heart resilience to insult in growth restricted lambs

    Science.gov (United States)

    Tare, Marianne; Parkington, Helena C; Wallace, Euan M; Sutherland, Amy E; Lim, Rebecca; Yawno, Tamara; Coleman, Harold A; Jenkin, Graham; Miller, Suzanne L

    2014-01-01

    Intrauterine growth restriction (IUGR) is associated with impaired cardiac function in childhood and is linked to short- and long-term morbidities. Placental dysfunction underlies most IUGR, and causes fetal oxidative stress which may impact on cardiac development. Accordingly, we investigated whether antenatal melatonin treatment, which possesses antioxidant properties, may afford cardiovascular protection in these vulnerable fetuses. IUGR was induced in sheep fetuses using single umbilical artery ligation on day 105–110 of pregnancy (term 147). Study 1: melatonin (2 mg h−1) was administered i.v. to ewes on days 5 and 6 after surgery. On day 7 fetal heart function was assessed using a Langendorff apparatus. Study 2: a lower dose of melatonin (0.25 mg h−1) was administered continuously following IUGR induction and the ewes gave birth normally at term. Lambs were killed when 24 h old and coronary vessels studied. Melatonin significantly improved fetal oxygenation in vivo. Contractile function in the right ventricle and coronary flow were enhanced by melatonin. Ischaemia–reperfusion-induced infarct area was 3-fold greater in IUGR hearts than in controls and this increase was prevented by melatonin. In isolated neonatal coronary arteries, endothelium-dependent nitric oxide (NO) bioavailability was reduced in IUGR, and was rescued by modest melatonin treatment. Melatonin exposure also induced the emergence of an indomethacin-sensitive vasodilation. IUGR caused marked stiffening of the coronary artery and this was prevented by melatonin. Maternal melatonin treatment reduces fetal hypoxaemia, improves heart function and coronary blood flow and rescues cardio-coronary deficit induced by IUGR. PMID:24710061

  5. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Kupchak Brian R

    2009-07-01

    Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

  6. MSCs transfected with hepatocyte growth factor or vascular endothelial growth factor improve cardiac function in the infarcted porcine heart by increasing angiogenesis and reducing fibrosis.

    Science.gov (United States)

    Lu, Fanglin; Zhao, Xianxian; Wu, Jun; Cui, Yong; Mao, Yanjun; Chen, Kebiao; Yuan, Yang; Gong, Dejun; Xu, Zhiyun; Huang, Shengdong

    2013-09-10

    Cell transplantation and gene therapy have been demonstrated to have beneficial effects after a myocardial infarction (MI). Here, we used a large animal model of MI to investigate the beneficial effects of mesenchymal stem cells (MSCs) transfected with hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) genes. A porcine MI model was created by balloon occlusion of the distal left anterior descending artery for 90 min followed by reperfusion. At 1 week after MI, the pigs were infused via the coronary vein with saline (n=8), MSCs + AdNull(n=8), MSC+VEGF(n=10), or MSC+HGF(n=10). Cardiac function and myocardial perfusion were evaluated by using echocardiography and gated cardiac perfusion imaging before and 4 weeks after transplantation. Morphometric and histological analyses were performed. All cell-implanted groups had better cardiac function than the saline control group. There were further functional improvements in the MSC+HGF group, accompanied by smaller infarct sizes, increased cell survival, and less collagen deposition. Blood vessel densities in the damaged area and cardiac perfusion were significantly greater in the MSC+AdNull group than in the saline control group, and further increased in the MSC+VEGF/HGF groups. Tissue fibrosis was significantly less extensive in the MSC and MSC+VEGF groups than in the saline control group and was most reduced in the MSC+HGF group. MSCs (alone or transfected with VEGF/HGF) delivered into the infarcted porcine heart via the coronary vein improved cardiac function and perfusion, probably by increasing angiogenesis and reducing fibrosis. MSC+HGF was superior to MSC+VEGF, possibly owing to its enhanced antifibrotic effect. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. An overview of methods using 13C for improved compound identification in metabolomics and natural products

    Science.gov (United States)

    Clendinen, Chaevien S.; Stupp, Gregory S.; Ajredini, Ramadan; Lee-McMullen, Brittany; Beecher, Chris; Edison, Arthur S.

    2015-01-01

    Compound identification is a major bottleneck in metabolomics studies. In nuclear magnetic resonance (NMR) investigations, resonance overlap often hinders unambiguous database matching or de novo compound identification. In liquid chromatography-mass spectrometry (LC-MS), discriminating between biological signals and background artifacts and reliable determination of molecular formulae are not always straightforward. We have designed and implemented several NMR and LC-MS approaches that utilize 13C, either enriched or at natural abundance, in metabolomics applications. For LC-MS applications, we describe a technique called isotopic ratio outlier analysis (IROA), which utilizes samples that are isotopically labeled with 5% (test) and 95% (control) 13C. This labeling strategy leads to characteristic isotopic patterns that allow the differentiation of biological signals from artifacts and yield the exact number of carbons, significantly reducing possible molecular formulae. The relative abundance between the test and control samples for every IROA feature can be determined simply by integrating the peaks that arise from the 5 and 95% channels. For NMR applications, we describe two 13C-based approaches. For samples at natural abundance, we have developed a workflow to obtain 13C–13C and 13C–1H statistical correlations using 1D 13C and 1H NMR spectra. For samples that can be isotopically labeled, we describe another NMR approach to obtain direct 13C–13C spectroscopic correlations. These methods both provide extensive information about the carbon framework of compounds in the mixture for either database matching or de novo compound identification. We also discuss strategies in which 13C NMR can be used to identify unknown compounds from IROA experiments. By combining technologies with the same samples, we can identify important biomarkers and corresponding metabolites of interest. PMID:26379677

  8. Compounding rifampin suspensions with improved injectability for nasogastric enteral feeding tube administration.

    Science.gov (United States)

    de Villiers, Melgardt M; Vogel, Laura; Bogenschutz, Monica C; Fingerhut, Bonnie J; D'Silva, Joseph B; Moore, Anne

    2010-01-01

    Often medications that have to be administered to patients via a nasogastric enteral feeding tubes are only available as tablets and capsules with no suitable commercial liquid alternatives. In such situations, pharmacists and nurses have to compound the tablets and capsule contents into liquid suspension formulations for dosing. The risk of occlusion of the enteral tubes during administration is reduced by employing liquid suspensions that are composed of small and uniform particles, not subject to rapid rates of settling, resistant to caking, and easily and uniformly re-suspended upon agitation. Present techniques often employ a manual process, such as a mortar and pestle, to accomplish the particle size reduction and subsequent incorporation into a suitable liquid diluent. A new compounding device has been invented that employs an automated wet-milling process in a single-use disposable plastic container to compound the suspensions. The two processes were compared using Rifampin capsules and various liquid diluents. A prototype version of the new device was employed in the experiments. The physical characteristics of the compounded suspensions were evaluated by determining sedimentation rate, sedimentation volume, and particle size and shape using laser light scattering, optical microscopy, and scanning electron microscopy techniques. The use characteristic of the compounded suspensions was evaluated using a nasogastric tube inject ability test. The results indicated that suspensions prepared using the new device were more resistant to sedimentation and caking and were easier to re-disperse into a uniform mixture by gentle shaking. The results were a consequence of the particles generated by the new device which were found to be smaller and more uniform in shape and size. The suspensions prepared using the new device did not cause blockage of the enteral feeding tubes in comparison to those prepared using a mortar and pastle. In conclusion, the results indicate

  9. Injectable shear-thinning hydrogels to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium

    Science.gov (United States)

    Gaffey, Ann C.; Chen, Minna H.; Venkataraman, Chantel M.; Trubelja, Alen; Rodell, Christopher B.; Dinh, Patrick V.; Hung, George; MacArthur, John W.; Soopan, Renganaden V.; Burdick, Jason A.; Atluri, Pavan

    2015-01-01

    OBJECTIVES The clinical translation of cell based therapies for ischemic heart disease has been limited due to low cell retention (myocardial borderzone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. METHODS EPCs (DiLDL+ VEGFR2+ CD34+) were harvested from adult male Wistar Rats, cultured, and then suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. STG-EPC constructs were injected at the borderzone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the eGFP+ EPCs from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (PBS injection), intramyocardial injection of EPCs alone (EPC), injection of the STG alone (STG), and treatment with the gel-EPC construct (STG-EPC). Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. RESULTS EPCs demonstrated viability within the STG. A marked increase in EPC engraftment was observed one-week post-injection within the treated myocardium with gel delivery when compared to EPC injection alone (17.2 ± 0.8 cells/HPF vs. 3.5 cells ± 1.3 cells/HPF, p = 0.0002). A statistically significant increase in vasculogenesis was noted with the STG-EPC construct (15.3 ± 5.8 vessels/HPF) when compared to control (p treatment compared to the control. CONCLUSIONS A novel injectable shear-thinning hyaluronic acid hydrogel seeded with EPCs enhanced cell retention and vasculogenesis after delivery to ischemic myocardium. This therapy limited adverse myocardial remodeling while preserving contractility. PMID:26293548

  10. Improving degradation of emerging organic compounds by applying chaotic advection in Managed Aquifer Recharge in randomly heterogeneous porous media

    Science.gov (United States)

    Rodríguez-Escales, P.; Fernà ndez-Garcia, D.; Drechsel, J.; Folch, A.; Sanchez-Vila, X.

    2017-05-01

    Improving degradation rates of emerging organic compounds (EOCs) in groundwater is still a challenge. Although their degradation is not fully understood, it has been observed that some substances are preferably degraded under specific redox conditions. The coupling of Managed Aquifer Recharge with soil aquifer remediation treatment, by placing a reactive layer containing organic matter at the bottom of the infiltration pond, is a promising technology to improve the rate of degradation of EOCs. Its success is based on assuming that recharged water and groundwater get well mixed, which is not always true. It has been demonstrated that mixing can be enhanced by inducing chaotic advection through extraction-injection-engineering. In this work, we analyze how chaotic advection might enhance the spreading of redox conditions with the final aim of improving degradation of a mix of benzotriazoles: benzotriazole, 5-methyl-benzotriazole, and 5-chloro-benzotriazole. The degradation of the first two compounds was fastest under aerobic conditions whereas the third compound was best degraded under denitrification conditions. We developed a reactive transport model that describes how a recharged water rich in organic matter mixes with groundwater, how this organic matter is oxidized by different electron acceptors, and how the benzotriazoles are degraded attending for the redox state. The model was tested in different scenarios of recharge, both in homogenous and in heterogenous media. It was found that chaotic flow increases the spreading of the plume of recharged water. Consequently, different redox conditions coexist at a given time, facilitating the degradation of EOCs.

  11. Cooking techniques improve the levels of bioactive compounds and antioxidant activity in kale and red cabbage.

    Science.gov (United States)

    Murador, Daniella Carisa; Mercadante, Adriana Zerlotti; de Rosso, Veridiana Vera

    2016-04-01

    The aim of this study is to investigate the effects of different home cooking techniques (boiling, steaming, and stir-frying) in kale and red cabbage, on the levels of bioactive compounds (carotenoids, anthocyanins and phenolic compounds) determined by high-performance liquid chromatography coupled with photodiode array and mass spectrometry detectors (HPLC-DAD-MS(n)), and on the antioxidant activity evaluated by ABTS, ORAC and cellular antioxidant activity (CAA) assays. The steaming technique resulted in a significant increase in phenolic content in kale (86.1%; pkale, steaming resulted in significant increases in antioxidant activity levels in all of the evaluation methods. In the red cabbage, boiling resulted in a significant increase in antioxidant activity using the ABTS assay but resulted in a significant decrease using the ORAC assay. According to the CAA assay, the stir-fried sample displayed the highest levels of antioxidant activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Approach to improve the productivity of bioactive compounds of the cyanobacterium Anabaena oryzae using factorial design

    Directory of Open Access Journals (Sweden)

    Ragaa A. Hamouda

    2017-09-01

    Full Text Available Cyanobacteria are one of the richest sources of biomedical relevant compounds with extensive therapeutic pharmaceutical applications and are also known as producer of intracellular and extracellular metabolites with diverse biological activities. The genus Anabaena sp. is known to produce antimicrobial compounds, like phycocyanin and others. The goal of this study was to optimize the production of these bioactive compounds. The Plackett–Burman experimental design was used to screen and evaluate the important medium components that influence the production of bioactive compounds. In this present study, eight independent factors including NaNO3, K2HPO4, MgSO4·7H2O, CaCl2, citric acid, ammonium ferric citrate, ethylene diamine tetraacetic acid disodium magnesium salt (EDTA-Na2Mg and Na2CO3 were surveyed and the effective variables for algal components production of Anabaena oryzae were determined using two-levels Plackett–Burman design. Results analysis showed that the best medium components were NaNO3 (2.25 g l−1; K2HPO4 (0.02 g l−1; MgSO4 (0.0375 g l−1; CaCl2 (0.018 g l−1; citric acid (0.009 g l−1; ammonium ferric citrate (0.009 g l−1 and EDTA-Na2 (0.0015 g l−1 respectively. The total chlorophyll-a, carotenoids, phenol, tannic acid and flavonoid contents in crude extract of Anabaena oryzae were determined. They were 47.7, 4.11, 0.256, 1.046 and 1.83 μg/ml, respectively. The antioxidant capacity was 62.81%.

  13. Improving compound quality through in vitro and in silico physicochemical profiling.

    Science.gov (United States)

    van de Waterbeemd, Han

    2009-11-01

    Many compounds entering clinical studies do not survive the numerous hurdles for a good pharmacological lead to a drug on the market. The reasons for attrition have been widely studied which resulted in more early attention to compound quality related to physical chemistry, drug metabolism and pharmacokinetics (DMPK), and toxicology/safety. This paper will briefly review current physicochemical in vitro assays and in silico predictions to support compound and library design through to lead optimization. The most important physicochemical properties include lipophilicity (log P/D), pKa, solubility, and permeability. These drive key ADMET properties such as absorption, cell penetration, access to the brain, volume of distribution, plasma protein binding, metabolism, and toxicity, as well as biopharmaceutical behavior. Much data are now available from medium- to high-throughput physchem and ADMET in vitro assays, either in the public domain (see, e.g., PubChem, PubMed) or in drug companies' in-house databases. Such data are increasingly being computer-modelled and used in predictive chemistry. New pipelining technology makes it easier to build and update QSAR models so that such models can use the latest available data to produce robust local and global predictive in silico ADMET models.

  14. Beyond DP4: an Improved Probability for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts.

    Science.gov (United States)

    Grimblat, Nicolás; Zanardi, María M; Sarotti, Ariel M

    2015-12-18

    The DP4 probability is one of the most sophisticated and popular approaches for the stereochemical assignment of organic molecules using GIAO NMR chemical shift calculations when only one set of experimental data is available. In order to improve the performance of the method, we have developed a modified probability (DP4+), whose main differences from the original DP4 are the inclusion of unscaled data and the use of higher levels of theory for the NMR calculation procedure. With these modifications, a significant improvement in the overall performance was achieved, providing accurate and confident results in establishing the stereochemistry of 48 challenging isomeric compounds.

  15. Removal of Metabolic Liabilities Enables Development of Derivatives of Procaspase-Activating Compound 1 (PAC-1) with Improved Pharmacokinetics.

    Science.gov (United States)

    Roth, Howard S; Botham, Rachel C; Schmid, Steven C; Fan, Timothy M; Dirikolu, Levent; Hergenrother, Paul J

    2015-05-14

    Procaspase-activating compound 1 (PAC-1) is an o-hydroxy-N-acylhydrazone that induces apoptosis in cancer cells by chelation of labile inhibitory zinc from procaspase-3. PAC-1 has been assessed in a wide variety of cell culture experiments and in vivo models of cancer, with promising results, and a phase 1 clinical trial in cancer patients has been initiated (NCT02355535). For certain applications, however, the in vivo half-life of PAC-1 could be limiting. Thus, with the goal of developing a compound with enhanced metabolic stability, a series of PAC-1 analogues were designed containing modifications that systematically block sites of metabolic vulnerability. Evaluation of the library of compounds identified four potentially superior candidates with comparable anticancer activity in cell culture, enhanced metabolic stability in liver microsomes, and improved tolerability in mice. In head-to-head experiments with PAC-1, pharmacokinetic evaluation in mice demonstrated extended elimination half-lives and greater area under the curve values for each of the four compounds, suggesting them as promising candidates for further development.

  16. [Corneal endothelial decompensation of iridocorneal endothelial syndrome treated by penetrating keratoplasty].

    Science.gov (United States)

    Chen, J; Liu, Z; Yu, L

    1996-07-01

    To evaluate the effect of penetrating keratoplasty in treatment of iridocorneal endothelial syndrome. The clinical and pathologic evaluation records were retrospectively analyzed for 8 cases with iridocorneal endothelial syndrome treated by penetrating keratoplasty. Postoperatively, they were followed for 3 months to 6 years. Seven cases had visual improvement, five buttons kept being transparent and three buttons became opaque. The penetrating keratoplasty is an effective measure for treatment of corneal endothelial decompensation of iridocorneal endothelial syndrome. However, the successful operative rate of this syndrome is lower than that in cases with corneal leucoma without vascularization.

  17. Cell-Based Screening Identifies Paroxetine as an Inhibitor of Diabetic Endothelial Dysfunction

    Science.gov (United States)

    Gerö, Domokos; Szoleczky, Petra; Suzuki, Kunihiro; Módis, Katalin; Oláh, Gabor; Coletta, Ciro; Szabo, Csaba

    2013-01-01

    We have conducted a phenotypic screening in endothelial cells exposed to elevated extracellular glucose (an in vitro model of hyperglycemia) to identify compounds that prevent hyperglycemia-induced reactive oxygen species (ROS) formation without adversely affecting cell viability. From a focused library of >6,000 clinically used drug-like and pharmacologically active compounds, several classes of active compounds emerged, with a confirmed hit rate of paroxetine, a clinically used antidepressant compound that has not been previously implicated in the context of hyperglycemia or diabetes. Paroxetine reduced hyperglycemia-induced mitochondrial ROS formation, mitochondrial protein oxidation, and mitochondrial and nuclear DNA damage, without interfering with mitochondrial electron transport or cellular bioenergetics. The ability of paroxetine to improve hyperglycemic endothelial cell injury was unique among serotonin reuptake blockers and can be attributed to its antioxidant effect, which primarily resides within its sesamol moiety. Paroxetine maintained the ability of vascular rings to respond to the endothelium-dependent relaxant acetylcholine, both during in vitro hyperglycemia and ex vivo, in a rat model of streptozotocin-induced diabetes. Thus, the current work identifies a novel pharmacological action of paroxetine as a protector of endothelial cells against hyperglycemic injury and raises the potential of repurposing of this drug for the experimental therapy of diabetic cardiovascular complications. PMID:23223176

  18. Improvement of charge separation in TiO{sub 2} by its modification with different tungsten compounds

    Energy Technology Data Exchange (ETDEWEB)

    Tryba, B., E-mail: beata.tryba@zut.edu.pl; Tygielska, M.; Grzeskowiak, M.; Przepiorski, J.

    2016-04-15

    Highlights: • Ammonium m-tungstate doped to TiO{sub 2} highly improved charge separation in TiO{sub 2}. • Negative electrokinetic potential of TiO{sub 2} facilitates holes migration to its surface. • Fast migration of holes to TiO{sub 2} surfaces increased yield of OH radicals formation. • Adsorption of dyes on photocatalyst increased its decomposition under visible light. - Abstract: Three different tungsten precursors were used for TiO{sub 2} modification: H{sub 2}WO{sub 4}, WO{sub 2}, and ammonium m-tungstate. It was proved that modification of TiO{sub 2} with tungsten compounds enhanced its photocatalytic activity through the improvement of charge separation. This effect was obtained by coating of TiO{sub 2} particles with tungsten compound, which changed their surficial electrokinetical potential from positive onto negative. The most efficient tungsten compound, which caused enhanced separation of free carriers was ammonium m-tungstate (AMT). Two dyes with different ionic potential were used for the photocatalytic decomposition. It appeared that cationic dye—Methylene Blue was highly adsorbed on the negatively charged surface of TiO{sub 2} modified by AMT and decomposed, however this photocatalyst was quickly deactivated whereas anionic dye—acid red was better adsorbed on the less acidic surface of TiO{sub 2} and was rapidly decomposed with almost the same rate in the five following cycles.

  19. Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Courtney Premer

    2015-05-01

    Interpretation: These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in patients with HF. These findings have significant clinical and biological implications for the use of MSCs in HF and other disorders associated with endothelial dysfunction.

  20. Fluorescence improvement of pyridylacrylonitrile by dimethylaminophenyl-substitutions: The effect of packing modes of conjugated compounds

    Science.gov (United States)

    Percino, M. Judith; Chapela, Víctor M.; Cerón, Margarita; Soriano-Moro, Guillermo; Castro, Maria Eugenia; Melendez, Francisco J.

    2013-02-01

    Four (dimethylamino)arylacrylonitrile derivatives in the solid state are presented. The compounds were characterized by single crystal X-ray diffraction to investigate the effects of substituents on the resulting crystals lattices and to examine the effects of the factors controlling their solid state on photochemical behavior. The molecules included 2-(phenyl)-3-(4-dimethylaminophenyl)acrylonitrile (I) 2-(2'-pyridyl)-3-(4-dimethylaminophenyl)-acrylonitrile (II), 2-(3'-pyridyl)-3-(4-dimethyl-aminophenyl)acrylonitrile (III) and 2-(3'-pyridyl)-3-(4-dimethylaminophenyl)acrylonitrile (IV). The dimethyl-, sbnd CN groups and the position of nitrogen atom in the pyridyl groups affected the nature of the molecular packing and consequently their fluorescence properties. The lattice of each compound is compared with acrylonitriles previously reported and the effect of substitution on the crystal properties with the strongest emission in solid state is examined. Based on analyses of molecular packing in the single crystals, the differences in the fluorescence could be attributed to aggregates that showed non-classical herringbone packing with π-π overlap between neighbor molecules. Also the crystal structure studies showed that the N atom position is located anti to the sbnd CN group, giving a more planar geometry. This N-dimethyl substituent for I-IV appears to be general for more planar ground-state geometry about the nitrogen atom and consistent with an "amino conjugation effect" to obtain sufficient quinoid structures.

  1. Improvement of biosynthesis and accumulation of bioactive compounds by elicitation in adventitious root cultures of Polygonum multiflorum.

    Science.gov (United States)

    Ho, Thanh-Tam; Lee, Jong-Du; Jeong, Cheol-Seung; Paek, Kee-Yoeup; Park, So-Young

    2018-01-01

    We examined the effects of abiotic (methyl jasmonate [MeJA] and salicylic acid [SA]) and biotic (yeast extract and chitosan) elicitors for improvement of bioactive compounds production on adventitious root cultures in Polygonum multiflorum. The application of yeast extract resulted in significantly (p ≤ 0.05) higher dry root biomass (9.98 g/L) and relative growth rate versus the control. Cultures treated with abiotic elicitors showed higher percentage of dry weight than the other samples. Low concentrations of all elicitors (50 μM MeJA and SA, and 50 mg/L yeast extract) improved secondary metabolite production except for chitosan, whose performance was worse than that of the control. HPLC analysis of various bioactive compounds revealed significantly higher elicitation efficiency for MeJA than for the other treatments, with an approximately 2-fold increase in root dry weight (22.08 mg/g DW) under 50 μM MeJA treatment versus the control (10.35 mg/g DW). We also investigated the feasibility of scaling up the production process by comparing shake flask cultures with 3- and 5-L balloon type bubble bioreactors (BTBB) using 50 μM MeJA as an elicitor. Growth and metabolite accumulation increased in BTBB compared with shake flask cultures. We detected a non-significant difference in biomass productivity between 3 and 5-L BTBB, but the efficiency of bioactive compound accumulation decreased with increasing volume. These findings will be useful for developing a pilot-scale P. multiflorum adventitious root cultivation process for high biomass and bioactive compound production to meet the demands for natural ingredients by the pharmaceutical and cosmetic industries without affecting the natural habitat of this plant.

  2. PCB 77 dechlorination products modulate pro-inflammatory events in vascular endothelial cells.

    Science.gov (United States)

    Eske, Katryn; Newsome, Bradley; Han, Sung Gu; Murphy, Margaret; Bhattacharyya, Dibakar; Hennig, Bernhard

    2014-05-01

    Persistent organic pollutants such as polychlorinated biphenyls (PCBs) are associated with detrimental health outcomes including cardiovascular diseases. Remediation of these compounds is a critical component of environmental policy. Although remediation efforts aim to completely remove toxicants, little is known about the effects of potential remediation byproducts. We previously published that Fe/Pd nanoparticles effectively dechlorinate PCB 77 to biphenyl, thus eliminating PCB-induced endothelial dysfunction using primary vascular endothelial cells. Herein, we analyzed the toxic effects of PCB congener mixtures (representative mixtures of commercial PCBs based on previous dechlorination data) produced at multiple time points during the dechlorination of PCB 77 to biphenyl. Compared with pure PCB 77, exposing endothelial cells to lower chlorinated PCB byproducts led to improved cellular viability, decreased superoxide production, and decreased nuclear factor kappa B activation based on duration of remediation. Presence of the parent compound, PCB 77, led to significant increases in mRNA and protein inflammatory marker expression. These data implicate that PCB dechlorination reduces biological toxicity to vascular endothelial cells.

  3. Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury.

    Science.gov (United States)

    Yamaya, Seiji; Ozawa, Hiroshi; Kanno, Haruo; Kishimoto, Koshi N; Sekiguchi, Akira; Tateda, Satoshi; Yahata, Kenichiro; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

    2014-12-01

    Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether low-energy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI. Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord. In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p

  4. Pattern optimization of compound optical film for uniformity improvement in liquid-crystal displays

    Science.gov (United States)

    Huang, Bing-Le; Lin, Jin-tang; Ye, Yun; Xu, Sheng; Chen, En-guo; Guo, Tai-Liang

    2017-12-01

    The density dynamic adjustment algorithm (DDAA) is designed to efficiently promote the uniformity of the integrated backlight module (IBLM) by adjusting the microstructures' distribution on the compound optical film (COF), in which the COF is constructed in the SolidWorks and simulated in the TracePro. In order to demonstrate the universality of the proposed algorithm, the initial distribution is allocated by the Bezier curve instead of an empirical value. Simulation results maintains that the uniformity of the IBLM reaches over 90% only after four rounds. Moreover, the vertical and horizontal full width at half maximum of angular intensity are collimated to 24 deg and 14 deg, respectively. Compared with the current industry requirement, the IBLM has an 85% higher luminance uniformity of the emerging light, which demonstrate the feasibility and universality of the proposed algorithm.

  5. Dietary proteins improve endothelial function under fasting conditions but not in the postprandial state, with no effects on markers of low-grade inflammation

    NARCIS (Netherlands)

    Teunissen-Beekman, K.F.M.; Dopheide, J.; Geleijnse, J.M.; Bakker, S.J.; Brink, E.J.; Leeuw, de P.W.; Schalkwijk, C.G.; Baak, van M.A.

    2015-01-01

    Endothelial dysfunction (ED) and low-grade inflammation (LGI) have a role in the development of CVD. The two studies reported here explored the effects of dietary proteins and carbohydrates on markers of ED and LGI in overweight/obese individuals with untreated elevated blood pressure. In the first

  6. Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

    Science.gov (United States)

    Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

    2016-09-01

    Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

  7. Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade : ACE-inhibition or AT(1)-receptor blockade?

    NARCIS (Netherlands)

    Buikema, H; Pinto, YM; van Gilst, WH

    Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endodiehal dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme

  8. Activation of endothelial toll-like receptor 3 impairs endothelial function.

    Science.gov (United States)

    Zimmer, Sebastian; Steinmetz, Martin; Asdonk, Tobias; Motz, Inga; Coch, Christoph; Hartmann, Evelyn; Barchet, Winfried; Wassmann, Sven; Hartmann, Gunther; Nickenig, Georg

    2011-05-27

    reactive oxygen species, increased apoptosis, and reduced migration. Injection of endothelial progenitor cells that had been incubated with polyinosine polycytidylic acid ex vivo hindered reendothelialization after carotid artery injury. Therefore, endothelial progenitor cell function was affected by TLR3 stimulation. Finally, apolipoprotein E-deficient/TLR3-deficient mice exhibited improved endothelial function compared with apolipoprotein E-deficient/TLR3(+/+) littermates. Immunorecognition of long double-stranded RNA by endothelial cells may be an important mechanism involved in endothelial cell activation and development of endothelial dysfunction.

  9. Exendin-4 Ameliorates Lipotoxicity-induced Glomerular Endothelial Cell Injury by Improving ABC Transporter A1-mediated Cholesterol Efflux in Diabetic apoE Knockout Mice.

    Science.gov (United States)

    Yin, Qing-Hua; Zhang, Rui; Li, Li; Wang, Yi-Ting; Liu, Jing-Ping; Zhang, Jie; Bai, Lin; Cheng, Jing-Qiu; Fu, Ping; Liu, Fang

    2016-12-16

    ATP-binding cassette transporter A1 (ABCA1), which promotes cholesterol efflux from cells and inhibits inflammatory responses, is highly expressed in the kidney. Research has shown that exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, promotes ABCA1 expression in multiple tissues and organs; however, the mechanisms underlying exendin-4 induction of ABCA1 expression in glomerular endothelial cells are not fully understood. In this study we investigated the effect of exendin-4 on ABCA1 in glomerular endothelial cells of diabetic kidney disease (DKD) and the possible mechanism. We observed a marked increase in glomerular lipid deposits in tissues of patients with DKD and diabetic apolipoprotein E knock-out (apoE-/-) mice by Oil Red O staining and biochemical analysis of cholesterol. We found significantly decreased ABCA1 expression in glomerular endothelial cells of diabetic apoE-/- mice and increased renal lipid, cholesterol, and inflammatory cytokine levels. Exendin-4 decreased renal cholesterol accumulation and inflammation and increased cholesterol efflux by up-regulating ABCA1. In human glomerular endothelial cells, GLP-1R-mediated signaling pathways (e.g. Ca2+/calmodulin-dependent protein kinase, cAMP/PKA, PI3K/AKT, and ERK1/2) were involved in cholesterol efflux and inflammatory responses by regulating ABCA1 expression. We propose that exendin-4 increases ABCA1 expression in glomerular endothelial cells, which plays an important role in alleviating renal lipid accumulation, inflammation, and proteinuria in mice with type 2 diabetes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Effects of phenolic compound addition to fractionated Novolak-based resists to improve resolution capability(2)

    Science.gov (United States)

    Sekiguchi, Atsushi; Matsumoto, Yoko; Sensu, Yoshihisa; Takei, Satoshi; Hanabata, Makoto; Tanaka, Hatsuyuki

    2017-03-01

    Novolak resists have been widely used in IC production and are used to this day in the production of flat panel displays (FPDs) and MEMS. However, with the advent of high-definition devices, FPDs must meet growing requirements for finer dimensions. These trends have generated requirements for higher sensitivity, higher resolution, and wider process margins for novolak resists. Using a lithography simulator with the goal of improving the performance of novolak resists, we examined various approaches to improving resist materials. This report discusses efforts to improve resolution and to broaden process margins using a novolak resin that exhibits a higher degree of fractionation than in the previous report (maximum fractionated resin) with the addition of low molecular weight phenol resins.

  11. The neuroprotective compound P7C3-A20 promotes neurogenesis and improves cognitive function after ischemic stroke.

    Science.gov (United States)

    Loris, Zachary B; Pieper, Andrew A; Dietrich, W Dalton

    2017-04-01

    Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established. Here, a transient middle cerebral artery occlusion in rats was followed by twice daily injection of P7C3-A20 or vehicle for 7days. P7C3-A20-treated rats performed significantly better than vehicle-treated controls in sensorimotor cylinder and grid-walk tasks, and in a chronic test of spatial learning and memory. These behavioral improvements with P7C3-A20 treatment were correlated with significantly decreased cortical and hippocampal atrophy, and associated with increased neurogenesis in the subventricular zone and hippocampal dentate gyrus subgranular zone. Furthermore, cerebral ischemia significantly reduced NAD in the cortex but P7C3-A20 treatment restored NAD to sham levels. Thus, P7C3-A20 treatment mitigates neurodegeneration and augments repair in the brain after focal ischemia, which translates into chronic behavioral improvement. This suggests a new therapeutic approach of using P7C3 compounds to safely augment NAD and thereby promote two independent processes critical to protecting the brain from ischemic stroke: mature neuron survival and postnatal neurogenesis throughout the post-ischemic brain. Published by Elsevier Inc.

  12. An investigation of various wavelength-shifting compounds for improving counting efficiency when 32P-cerenkov radiation is measured in aqueous samples

    NARCIS (Netherlands)

    Ginkel, G. van

    Various water-soluble wavelength-shifting compounds were investigated to assess their suitability for the improvement of counting efficiency when erenkov radiation from phosphorous-32 is measured in a liquid scintillation counter. Of these compounds esculin, β-methyl-umbelliferon and sodium

  13. Blue and Red LED Illumination Improves Growth and Bioactive Compounds Contents in Acyanic and Cyanic Ocimum basilicum L. Microgreens

    Directory of Open Access Journals (Sweden)

    Andrei Lobiuc

    2017-11-01

    Full Text Available Microgreens are an excellent source of health-maintaining compounds, and the accumulation of these compounds in plant tissues may be stimulated by exogenous stimuli. While light quality effects on green basil microgreens are known, the present paper aims at improving the quality of acyanic (green and cyanic (red basil microgreens with different ratios of LED blue and red illumination. Growth, assimilatory and anthocyanin pigments, chlorophyll fluorescence, total phenolic, flavonoids, selected phenolic acid contents and antioxidant activity were assessed in microgreens grown for 17 days. Growth of microgreens was enhanced with predominantly blue illumination, larger cotyledon area and higher fresh mass. The same treatment elevated chlorophyll a and anthocyanin pigments contents. Colored light treatments decreased chlorophyll fluorescence ΦPSII values significantly in the green cultivar. Stimulation of phenolic synthesis and free radical scavenging activity were improved by predominantly red light in the green cultivar (up to 1.87 fold and by predominantly blue light in the red cultivar (up to 1.73 fold. Rosmarinic and gallic acid synthesis was higher (up to 15- and 4-fold, respectively, compared to white treatment in predominantly blue illumination. Red and blue LED ratios can be tailored to induce superior growth and phenolic contents in both red and green basil microgreens, as a convenient tool for producing higher quality foods.

  14. Improved mechanical and functional properties of elastomer/graphite nanocomposites prepared by latex compounding

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jian [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Key Laboratory on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Tian Ming [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Jia Qingxiu [Key Laboratory on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Shi Junhong [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Zhang Liqun [Key Laboratory for Nano-materials, Beijing University of Chemical Technology, Ministry of Education of China, Beijing 100029 (China); Key Laboratory on Preparation and Processing of Novel Polymer Materials, Beijing University of Chemical Technology, Beijing 100029 (China)], E-mail: zhanglq@mail.buct.edu.cn; Lim Szuhui; Yu Zhongzhen [Centre for Advanced Materials Technology (CAMT), School of Aerospace, Mechanical and Mechatronic Engineering (J07), University of Sydney, Sydney, NSW 2006 (Australia); Mai Yiuwing [Centre for Advanced Materials Technology (CAMT), School of Aerospace, Mechanical and Mechatronic Engineering (J07), University of Sydney, Sydney, NSW 2006 (Australia)], E-mail: y.mai@usyd.edu.au

    2007-10-15

    The facile latex approach has been adopted to finely incorporate graphite nanosheets into elastomeric polymer matrix to obtain high-performance elastomeric nanocomposites with improved mechanical properties and functional properties. Scanning electron microscopy, transmission electron microscopy and X-ray diffraction experiments show that the nanostructures of the final nanocomposites exhibit a high degree of exfoliation and intercalation of graphite in the nitrile-butadiene rubber (NBR) matrix. Mechanical and dynamic-mechanical tests demonstrate that the NBR/graphite nanocomposites possess greatly increased elastic modulus and tensile strength, and desirably strong interfaces. The unexpected self-crosslinking of elastomer/graphite nanocomposites was discovered and then verified by oscillating disc rheometry and equilibrium swelling experiments. After critically examining various polymer types by X-ray photoelectron spectroscopy, electron spin resonance and Fourier transform infrared spectroscopy, a radical initiation mechanism was proposed to explain the self-crosslinking reaction. These NBR/graphite nanocomposites possess significantly improved wear resistance and gas barrier properties, and superior electrical/thermal conductivity. Such versatile functional properties make NBR nanocomposites a promising new class of advanced materials.

  15. Water deficit improved the capacity of arbuscular mycorrhizal fungi (AMF) for inducing the accumulation of antioxidant compounds in lettuce leaves.

    Science.gov (United States)

    Baslam, Marouane; Goicoechea, Nieves

    2012-07-01

    Lettuce, a major food crop within the European Union and the most used for the so-called 'Fourth Range' of vegetables, can associate with arbuscular mycorrhizal fungi (AMF). Mycorrhizal symbiosis can stimulate the synthesis of secondary metabolites, which may increase plant tolerance to stresses and enhance the accumulation of antioxidant compounds potentially beneficial to human health. Our objectives were to assess (1) if the application of a commercial formulation of AMF benefited growth of lettuce under different types and degrees of water deficits; (2) if water restrictions affected the nutritional quality of lettuce; and (3) if AMF improved the quality of lettuce when plants grew under reduced irrigation. Two cultivars of lettuce consumed as salads, Batavia Rubia Munguía and Maravilla de Verano, were used in the study. Four different water regimes were applied to both non-mycorrhizal and mycorrhizal plants: optimal irrigation (field capacity [FC]), a water regime equivalent to 2/3 of FC, a water regime equivalent to 1/2 of FC and a cyclic drought (CD). Results showed that mycorrhizal symbiosis improved the accumulation of antioxidant compounds, mainly carotenoids and anthocyanins, and to a lesser extent chlorophylls and phenolics, in leaves of lettuce. These enhancements were higher under water deficit than under optimal irrigation. Moreover, shoot biomass in mycorrhizal lettuces subjected to 2/3 of FC were similar to those of non-mycorrhizal plants cultivated under well-watered conditions. In addition, lettuces subjected to 2/3 FC had similar leaf RWC than their respective well-watered controls, regardless of mycorrhizal inoculation. Therefore, results suggest that mycorrhizal symbiosis can improve quality of lettuce and may allow restrict irrigation without reducing production.

  16. Improved electroanalytical characteristics for flumetralin determination in the presence of surface active compound.

    Science.gov (United States)

    Guziejewski, Dariusz; Smarzewska, Sylwia; Metelka, Radovan; Nosal-Wiercińska, Agnieszka; Ciesielski, Witold

    2017-01-01

    The use of square wave voltammetry (SWV) and square wave adsorptive stripping voltammetry (SWAdSV) in conjunction with a cyclic renewable silver amalgam film electrode for the determination of flumetralin is presented. Poor separation of two overlapped reduction peaks is significantly improved when hexadecyltrimethylammonium bromide is used as a component of the supporting electrolyte solution (together with BR buffer pH 9.5). The SW technique parameters were investigated and found optimal as follows: frequency 50 Hz, amplitude 40 mV, and step potential 5 mV. Accumulation time and potential were studied to select the optimal conditions in adsorptive voltammetry. The analytical curve was linear for the flumetralin concentration range from 1.0 × 10(-6) to 1.0 × 10(-5) mol dm(-3) and from 5.0 × 10(-9) to 1.0 × 10(-7) mol dm(-3) for SWV and SWAdSV, respectively. Detection limit of 6.5 × 10(-10) mol dm(-3) was calculated for accumulation time 60 s at -0.2 V. The repeatability of the method was determined at a flumetralin concentration level equal to 5.0 × 10(-9) mol dm(-3) and expressed as %RSD = 5.0% (n = 6). The proposed method was applied and validated successfully by studying the recovery of herbicide content in spiked environmental samples.

  17. Hypothesis: Co-transfer of genuine embryos and implantation-promoting compounds via artificial containers improve endometrium receptivity.

    Science.gov (United States)

    Celik, Onder; Acet, Mustafa; Celik, Sudenaz; Sahin, Levent; Koc, Onder; Celik, Nilufer

    2017-06-01

    As with other organs endometrial functions are altered with the advancing age. Age related decrease in reproductive functions leads to decline in the number of oocytes retrieved and the synthesis of endometrial receptivity molecules. Despite the significant improvement in assisted reproductive technologies we do not have so many options to enhance endometrial receptivity. Due to lack of drugs having endometrium receptivity enhancement properties, oocyte donation seems to be the only solution for women with implantation failure. The euploid oocytes come from young and healthy donors may overcome age associated endometrial receptivity defect. Nevertheless, many reasons restrict us from using oocyte donation in women with implantation failure. We, therefore, hypothesized that by mimicking a young blastocyst's effect on endometrium, the transfer of genuine embryos and implantation-promoting compounds together might be the new treatment option for infertile women with recurrent implantation failure. Artificial beads, MI or GV oocytes, and empty zona can be used as a container for intrauterine replacement of implantation-promoting compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Endothelial replacement: the limbal pocket approach.

    Science.gov (United States)

    Terry, Mark A

    2003-03-01

    The limbal pocket approach to endothelial replacement shows extraordinary promise in fulfilling the ideal goals of surgical treatment for endothelial dysfunction. From its inception, DLEK surgery has demonstrated that, by preserving the limbus and eliminating surface corneal incisions and sutures, the corneal topography can be stabilized with little change from preoperative measurements of astigmatism and corneal power. The surgical dissection planes of DLEK surgery are inherently stronger than that of PK or any other form of endothelial replacement, allowing early stability of the refraction and making the eye safer from blunt trauma over the long term. Further work with DLEK must be performed in perfecting the optical properties of the stromal interface before this technique can be used widely; however, as technology and techniques improve, DLEK surgery holds the promise of being the ideal method for endothelial replacement in the 21st century.

  19. Reducing Visit-To-Visit Variability in Systolic Blood Pressure for Improving the Progression of Carotid Atherosclerosis and Endothelial Dysfunction in Patients with Hypertension Management.

    Science.gov (United States)

    Song, Hongbin; Liu, Zhendong; Zhao, Yingxin; Ye, Lin; Lu, Fanghong; Zhang, Hua; Diao, Yutao; Xu, Jianchao

    2014-06-01

    Visit-to-visit variability (VVV) in blood pressure (BP) creates challenges to hypertension control and was independent associated with increased all-cause mortality in hypertensive patients. The major goal of the present study was to investigate the association of VVV in systolic (S)BP with progression of carotid atherosclerosis and en-dothelial dysfunction in on-treated hypertensive patients. Overall, 356 hypertensive patients were enrolled and completed the trial. Clinic BP was measured at baseline and at 3 monthly thereafter. Carotid artery ultrasound and endothelial function were evaluated at baseline and annually follow-up visit. VVV in BP was assessed by standard deviation (SD) and coefficient of variation (CV) of serial follow-up BP measurements. The patients were divided into low, middle, and high group by tertile of SD in SBP. Decrease percentage of maximum intima-media thickness (IMT) and stiffness index β and increase percentage of brachial flow-mediated dilation (FMD) and nitric oxide (NO) in lower groups were significant greater than in higher groups (P < 0.05). Change percentage of stiffness index β and endothelin-1 positively, and change percentage of FMD and NO negatively correlated with SD, CV, maximum, and delta of SBP (P < 0.05). SD and CV of SBP were risk factors for change percentage of IMT, stiffness index β, FMD, NO, and endothelin-1 independently of other influential factors, such as age, and mean SBP. Excessive VVV in SBP maybe increase carotid atherosclerosis and impair endothelial function in on-treated hypertensive patients. Reducing VVV in SBP is benefit for patients with hypertension management.

  20. Protein hydrolysate from canned sardine and brewing by-products improves TNF-α-induced inflammation in an intestinal-endothelial co-culture cell model.

    Science.gov (United States)

    Vieira, Elsa F; Van Camp, John; Ferreira, Isabel M P L V O; Grootaert, Charlotte

    2017-07-17

    The anti-inflammatory activity of sardine protein hydrolysates (SPH) obtained by hydrolysis with proteases from brewing yeast surplus was ascertained. For this purpose, a digested and desalted SPH fraction with molecular weight lower than 10 kDa was investigated using an endothelial cell line (EA.hy926) as such and in a co-culture model with an intestinal cell line (Caco-2). Effects of SPH SPH SPH SPH SPH to be used as a functional food with anti-inflammatory properties.

  1. Polyphenols in preventing endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Sylwia Biegańska-Hensoldt

    2017-03-01

    Full Text Available One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions.Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS and increased production of nitric oxide (NO and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules – sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.

  2. Strategies to reverse endothelial dysfunction in diabetic nephropathy

    OpenAIRE

    Badal, Shawn S.; Danesh, Farhad R.

    2012-01-01

    Endothelial dysfunction underlies the basic pathophysiology of microvascular complications of diabetes. Endothelial dysfunction is associated with impaired nitric oxide (NO) availability. Since NO production is tightly regulated by endothelial nitric oxide synthase (eNOS), several therapeutic strategies have been investigated and proposed to improve eNOS bioavailability in the vasculature. The findings of Cheng et al. suggest that increased availability of eNOS may be an effective strategy in...

  3. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.

    Science.gov (United States)

    Grassi, Davide; Draijer, Richard; Schalkwijk, Casper; Desideri, Giovambattista; D'Angeli, Anatolia; Francavilla, Sandro; Mulder, Theo; Ferri, Claudio

    2016-11-16

    (1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p tea consumption counteracted FMD impairment (p tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

  4. Daming capsule restores endothelial dysfunction induced by high-fat diet

    Directory of Open Access Journals (Sweden)

    Zhang Rong

    2012-03-01

    Full Text Available Abstract Background Daming capsule (DMC, a traditional Chinese formula, has a lipid-modulating action with reduced adverse side effects as compared with other lipid lowering compounds. Since endothelial dysfunction often accompanies the hyperlipidemic state, we hypothesize that DMC might restore endothelial dysfunction produced by a high-fat (HF diet. Importantly, we also investigate possible mechanisms involved in mediating the effects of DMC on vascular reactivity. Methods Rats were divided into four groups: control, HF diet, HF mixed DMC diet, HF mixed atorvastatin (ATV diet. After 30 days, the thoracic cavity was exposed to remove the thoracic aorta for (i histological examination; (ii measurement of endothelial nitric oxide synthase (eNOS by western blot; and (iii tension study of thoracic aortic ring. Results HF diet induced significant attenuation in the contraction and relaxation of rat aortic rings. Treatment with DMC significantly improved the relaxation of the aortic rings as compared with those from HF rats (P + channels (KATP on the structure and/or function. DMC exerted the same protective effect as ATV, a positive control drug, on vascular injury produced by HF diet. Conclusion DMC partially protects the aorta from HF-induced endothelial dysfunction via upregulation of the expression of eNOS.

  5. New continuous air pumping technique to improve clinical outcomes of descemet-stripping automated endothelial keratoplasty in asian patients with previous ahmed glaucoma valve implantation.

    Directory of Open Access Journals (Sweden)

    Chang-Min Liang

    Full Text Available BACKGROUND: To evaluate the outcomes of Descemet-stripping automated endothelial keratoplasty (DSAEK with the use of continuous air pumping technique in Asian eyes with previous Ahmed glaucoma valve implantation. METHODS: The DSAEK procedure was modified in that complete air retention of the anterior chamber was maintained for 10 min using continuous air pumping at 30 mm Hg. The primary outcome measurement was graft survival, and postoperative clinical features including, rate of graft detachment, endothelial cell count, intraocular pressure (IOP, surgical time and cup/disc ratio were also recorded. RESULTS: A total of 13 eyes of 13 patients which underwent modified DSAEK and 6 eyes of 6 patients which underwent conventional DSAEK were included. There was a significant difference in graft survival curves between two groups (P = 0.029; the 1-year graft survival rates were estimated as 100% and 66.7% for patients with modified DSAEK and those with traditional DSAEK, respectively. The rate of graft detachment were 0% and 33.3% for the modified DSAEK and conventional DSAEK groups, respectively (P = 0.088. The significantly lowered surgical time for air tamponade was noted in the modified DSAEK group compared to that in the conventional DSAEK group [median (IQR: 10.0 (10.0, 10.0 min vs. 24.5 (22.0, 27.0 min; P<0.001] Postoperatively, patients in the modified DSAEK group had significantly lower IOP as compared to the conventional DSAEK group [12.0 (11.0, 15.0 mm Hg vs. 16.0 (15.0, 18.0 mm Hg; P = 0.047]. Modified DSAEK patients had higher endothelial cell counts as compared to conventional DSAEK patients [2148.0 (1964.0, 2218.0 vs. 1529.0 (713.0, 2014.0], but the difference did not reach statistical significance (P = 0.072. CONCLUSIONS: New continuous air pumping technique in DSAEK can be performed safely and effectively in patients with prior GDDs placement who have corneal failure.

  6. Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities

    OpenAIRE

    Aman, Jurjan; Weijers, Ester M.; Geerten P van Nieuw Amerongen; Malik, Asrar B.; van Hinsbergh, Victor W.M.

    2016-01-01

    Despite considerable progress in the understanding of endothelial barrier regulation and the identification of approaches that have the potential to improve endothelial barrier function, no drug- or stem cell-based therapy is presently available to reverse the widespread vascular leak that is observed in acute respiratory distress syndrome (ARDS) and sepsis. The translational gap suggests a need to develop experimental approaches and tools that better mimic the complex environment of the micr...

  7. Targeted endothelial nanomedicine for common acute pathological conditions.

    Science.gov (United States)

    Shuvaev, Vladimir V; Brenner, Jacob S; Muzykantov, Vladimir R

    2015-12-10

    Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal

  8. Dietary proteins improve endothelial function under fasting conditions but not in the postprandial state, with no effects on markers of low-grade inflammation.

    Science.gov (United States)

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; Schalkwijk, Casper G; van Baak, Marleen A

    2015-12-14

    Endothelial dysfunction (ED) and low-grade inflammation (LGI) have a role in the development of CVD. The two studies reported here explored the effects of dietary proteins and carbohydrates on markers of ED and LGI in overweight/obese individuals with untreated elevated blood pressure. In the first study, fifty-two participants consumed a protein mix or maltodextrin (3×20 g/d) for 4 weeks. Fasting levels and 12 h postprandial responses of markers of ED (soluble intercellular adhesion molecule 1 (sICAM), soluble vascular cell adhesion molecule 1 (sVCAM), soluble endothelial selectin and von Willebrand factor) and markers of LGI (serum amyloid A, C-reactive protein and sICAM) were evaluated before and after intervention. Biomarkers were also combined into mean Z-scores of ED and LGI. The second study compared 4 h postprandial responses of ED and LGI markers in forty-eight participants after ingestion of 0·6 g/kg pea protein, milk protein and egg-white protein. In addition, postprandial responses after maltodextrin intake were compared with a protein mix and sucrose. The first study showed significantly lower fasting ED Z-scores and sICAM after 4 weeks on the high-protein diet (P≤0·02). The postprandial studies found no clear differences of ED and LGI between test meals. However, postprandial sVCAM decreased more after the protein mix compared with maltodextrin in both studies (P≤0·04). In conclusion, dietary protein is beneficial for fasting ED, but not for fasting LGI, after 4 weeks of supplementation. On the basis of Z-scores, postprandial ED and LGI were not differentially affected by protein sources or carbohydrates.

  9. You're Only as Old as Your Arteries: Translational Strategies for Preserving Vascular Endothelial Function with Aging

    Science.gov (United States)

    Kaplon, Rachelle E.; Gioscia-Ryan, Rachel A.; LaRocca, Thomas J.

    2014-01-01

    Endothelial dysfunction develops with age and increases the risk of age-associated vascular disorders. Nitric oxide insufficiency, oxidative stress, and chronic low-grade inflammation, induced by upregulation of adverse cellular signaling processes and imbalances in stress resistance pathways, mediate endothelial dysfunction with aging. Healthy lifestyle behaviors preserve endothelial function with aging by inhibiting these mechanisms, and novel nutraceutical compounds that favorably modulate these pathways hold promise as a complementary approach for preserving endothelial health. PMID:24985329

  10. Inhibition of SREBP transcriptional activity by a boron-containing compound improves lipid homeostasis in diet-induced obesity.

    Science.gov (United States)

    Zhao, Xiaoping; Xiaoli; Zong, Haihong; Abdulla, Arian; Yang, Ellen S T; Wang, Qun; Ji, Jun-Yuan; Pessin, Jeffrey E; Das, Bhaskar C; Yang, Fajun

    2014-07-01

    Dysregulation of lipid homeostasis is intimately associated with obesity, type 2 diabetes, and cardiovascular diseases. Sterol regulatory-element binding proteins (SREBPs) are the master regulators of lipid biosynthesis. Previous studies have shown that the conserved transcriptional cofactor Mediator complex is critically required for the SREBP transcriptional activity, and recruitment of the Mediator complex to the SREBP transactivation domains (TADs) is through the MED15-KIX domain. Recently, we have synthesized several boron-containing small molecules. Among these novel compounds, BF175 can specifically block the binding of MED15-KIX to SREBP1a-TAD in vitro, resulting in an inhibition of the SREBP transcriptional activity and a decrease of SREBP target gene expression in cultured hepatocytes. Furthermore, BF175 can improve lipid homeostasis in the mouse model of diet-induced obesity. Compared with the control, BF175 treatment decreased the expression of SREBP target genes in mouse livers and decreased hepatic and blood levels of lipids. These results suggest that blocking the interaction between SREBP-TADs and the Mediator complex by small molecules may represent a novel approach for treating diseases with aberrant lipid homeostasis. © 2014 by the American Diabetes Association.

  11. Bioavailability of Heavy Metals in Soil: Impact on Microbial Biodegradation of Organic Compounds and Possible Improvement Strategies

    Directory of Open Access Journals (Sweden)

    Balakrishna Pillay

    2013-05-01

    Full Text Available Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation, treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals.

  12. Bioavailability of Heavy Metals in Soil: Impact on Microbial Biodegradation of Organic Compounds and Possible Improvement Strategies

    Science.gov (United States)

    Olaniran, Ademola O.; Balgobind, Adhika; Pillay, Balakrishna

    2013-01-01

    Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation), treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals. PMID:23676353

  13. Bioavailability of heavy metals in soil: impact on microbial biodegradation of organic compounds and possible improvement strategies.

    Science.gov (United States)

    Olaniran, Ademola O; Balgobind, Adhika; Pillay, Balakrishna

    2013-05-15

    Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation), treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals.

  14. Olive oil bioactive compounds increase body weight, and improve gut health and integrity in gilthead sea bream (Sparus aurata).

    Science.gov (United States)

    Gisbert, Enric; Andree, Karl B; Quintela, José C; Calduch-Giner, Josep A; Ipharraguerre, Ignacio R; Pérez-Sánchez, Jaume

    2017-02-01

    An olive oil bioactive extract (OBE) rich in bioactive compounds like polyphenols, triterpenic acids, long-chain fatty alcohols, unsaturated hydrocarbons, tocopherols and sterols was tested (0, 0·08, 0·17, 0·42 and 0·73 % OBE) in diets fed to sea bream (Sparus aurata) (initial weight: 5·4 (sd 1·2) g) during a 90-d trial (four replicates). Fish fed diets containing 0·17 and 0·42 % OBE were 5 % heavier (61·1 (sd 1·6) and 60·3 (sd 1·1) g, respectively) than those of the control group (57·0 (sd 0·7) g), although feed conversion ratio and specific feed intake did not vary. There were no differences in lipid peroxidation (LPO) levels, catalase, glutathione reductase and glutathione S-transferase activities in the intestine and liver, although there was a tendency of lower intestinal and hepatic LPO levels in fish fed OBE diets. No differences in villus size were found among treatments, whereas goblet cell density in the control group was on average14·3 % lower than in fish fed OBE diets. The transcriptomic profiling of intestinal markers, covering different biological functions like (i) cell differentiation and proliferation, (ii) intestinal permeability, (iii) enterocyte mass and epithelial damage, (iv) IL and cytokines, (v) pathogen recognition receptors and (vi) mitochondria function, indicated that among the eighty-eight evaluated genes, twenty-nine were differentially expressed (0·17 % OBE diet), suggesting that the additive has the potential of improving the condition and defensive role of the intestine by enhancing the maturation of enterocytes, reducing oxidative stress, improving the integrity of the intestinal epithelium and enhancing the intestinal innate immune function, as gene expression data indicated.

  15. A diet enriched with mackerel (Scomber scombrus)-derived products improves the endothelial function in a senior population (Prevención de las Enfermedades Cardiovasculares: Estudio Santoña--PECES project).

    Science.gov (United States)

    de Berrazueta, J R; Gómez de Berrazueta, J M; Amado Señarís, J A; Peña Sarabia, N; Fernández Viadero, C; García-Unzueta, M T; Sáez de Adana, M; Sanchez Ovejero, C J; Llorca, J

    2009-03-01

    Regular consumption of fish reduces cardiovascular risks. Here, we investigate if the consumption of products with mackerel (Scomber scombrus) with 8.82 g of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) content per 100 g of product improves parameters of endothelial function in a controlled population. Subjects maintained a 12-week diet with products with mackerel. The population consisted of 58 senior subjects (12 withdrawals, 25 women), aged 82.08 +/- 8.13 years (Group A). Twenty-three senior subjects (13 women) on a regular diet were used as the control group (Group B). Subjects of Group A received 57 portions throughout 12 weeks (four to five portions a week of products with a mean EPA + DHA content of 2.5 g a day). A continuous follow-up and a final evaluation were performed to determine the level of consumption. Plasma samples were stored at -70 degrees C for a biochemical study. Endothelial function was analysed by reactive hyperemia with a mercury strain gauge plethysmography with measurement of blood flow in the forearm, both baseline and at the end of the 12-week diet. Endothelium-dependent vasodilatation significantly increased in Group A subjects (P < 0.001). No changes were found in Group B. The subgroup analyses showed that improvements were produced in Group A subjects without cardiovascular disease (P < 0.001). Nitrites/nitrates and von Willebrand factor plasma concentrations were higher in participants after the 12-week diet. The consumption of mackerel meat products improves endothelium-dependent, flow-mediated vasodilatation in a senior population. This finding might explain some of the cardioprotective effects of fish consumption.

  16. Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.

    Directory of Open Access Journals (Sweden)

    Ikechukwu Okoli

    Full Text Available Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans-C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay.

  17. An extract from medical leech improve the function of endothelial cells in vitro and attenuates atherosclerosis in ApoE null mice by reducing macrophages in the lesions.

    Science.gov (United States)

    Wang, Yao; Zhao, Xin; Wang, Yun-Shan; Song, Shu-Liang; Liang, Hao; Ji, Ai-Guo

    2014-12-05

    Medicinal leech has been widely used as a traditional Chinese medicine in cardiovascular diseases. However, its pharmaceutical effect is not fully revealed. The goal of this study was to determine whether a leech extract has the effect of anti-atherosclerosis in ApoE −/− mice and the mechanism of this effect. In vivo experiments: ApoE −/− mice fed on high-cholesterol diet were separated into 5 groups. Control group was administrated with normal water; leech extract of low dose treatment group was given a leech extract of 0.02 g/kg/d; leech extract of medium dose treatment group was given a leech extract of 0.1 g/kg/d; leech extract of high dose treatment group was given a leech extract of 0.5 g/kg/d; simvastatin group was given simvastatin of 10 mg/kg/d. Leech extract significantly reduced atherosclerotic lesions in aortic root compared with control group. And the number of macrophage in or around the atherosclerosis plaque is significantly reduced in the leech extract groups compared with control group. In vitro experiments: human endothelial cell line, EA.hy926, was induced with TNF-α to perform endothelial dysfunction. Control group: EA.hy926 cells with no special treatment; TNF-α group: EA.hy926 cells were induced by 10 ng/ml TNF-α for 6 h; leech extract only group: EA.hy926 cells were treated with 200 mg/ml leech extract only; leech extract and TNF-α group: 200 mg/ml leech extract was applied before TNF-α induction. Protein and mRNA level were detected in each group, leech extract can decrease the expression of intercellular adhesion factor (ICAM-1) and monocyte chemotactic protein (MCP-1) compared with TNF-α group. Furthermore, it showed less adhesion and migration of THP-1 cells to EA.hy926 cells in the adhesion assay and transwell assay. The NF-κB translation to nucleus was blocked by leech extract in the NF-κB translocation assay. Leech extract could obviously attenuate the area of atherosclerosis lesion in ApoE −/− mice. And this

  18. Increased leukocyte rho kinase (ROCK) activity and endothelial dysfunction in cigarette smokers

    OpenAIRE

    Hidaka, Takayuki; Hata, Takaki; Soga, Junko; Fujii, Yuichi; Idei, Naomi; Fujimura, Noritaka; Kihara, Yasuki; Noma, Kensuke; Liao, James K.; Higashi, Yukihito

    2010-01-01

    Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. Although smoking is associated with endothelial dysfunction and ROCK inhibitors improve endothelial function in smokers, it is not known whether ROCK activity is increased in smokers and whether this correlates with endothelial dysfunction. The purpose of this study was to evaluate the relationship between ROCK activity and endothelial function in smokers. We evaluated flow-mediated vasodilat...

  19. Pulse seed germination improves antioxidative activity of phenolic compounds in stripped soybean oil-in-water emulsions.

    Science.gov (United States)

    Xu, Minwei; Jin, Zhao; Peckrul, Allen; Chen, Bingcan

    2018-06-01

    The purpose of this study was to investigate antioxidative activity of phenolic compounds extracted from germinated pulse seed including chickpeas, lentils and yellow peas. Phenolic compounds were extracted at different germination time and total phenolic content was examined by Folin Ciocalteu's reaction. Antioxidative activity of extracts was characterized by in vitro assay including 2, 2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH), oxygen radical absorbance capacity (ORAC), iron-binding assay, and in stripped soybean oil-in-water emulsions. The results suggested that germination time is critical for phenolic compounds production. The form variation of phenolic compounds influenced the antioxidative activity of phenolic compounds both in vitro assay and in emulsion systems. Soluble bound phenolic compounds showed higher antioxidative ability in emulsion system with the order of chickpea > yellow pea > lentil. On the basis of these results, soluble bound phenolic compounds may be considered as a promising natural antioxidant to prevent lipid oxidation in foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

    Science.gov (United States)

    Boon, Evan A J; Croft, Kevin D; Shinde, Sujata; Hodgson, Jonathan M; Ward, Natalie C

    2017-09-20

    A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

  1. An improved colorimetric method for the determination of proline in the presence of other ninhydrin-positive compounds

    Science.gov (United States)

    Wren, J. J.; Wiggall, P. H.

    1965-01-01

    1. The conditions required for sensitive and specific colorimetric determination of proline with acidified ninhydrin were investigated. 2. A method applicable to protein samples was developed. 3. The only compound found to interfere appreciably was a hydroxyproline. PMID:14342233

  2. Overexpression of Jagged1 Ameliorates Aged Rat-Derived Endothelial Progenitor Cell Functions and Improves Its Transfusion Efficiency for Rat Balloon-Induced Arterial Injury.

    Science.gov (United States)

    Zhu, Guangxu; Wang, Jinxiang; Song, Mingbao; Zhou, Fang; Fu, Dagan; Ruan, Guangping; Bai, Yingying; Yu, Zhengping; Zhang, Leilei; Zhu, Xiangqing; Huang, Lan; Pang, Rongqing; Pan, Xinghua

    2017-05-01

    Endothelial progenitor cell (EPC) has significant age-dependent alterations in properties, but the role of Jagged1 in aging-induced decline of EPC functions remains unclear. 2- and 20-month old healthy male Sprague-Dawley rats were used in present study. Jagged1 gene transfection was performed in EPC isolated from aged (AEPC) and young rats (YEPC), respectively. Experiments were divided into 4 groups: (1) pIRES2-EGFP (PE) group, (2) PE-combined N-[N-(3, 5-difluoro-phenacetyl)-1- alany1]-S-phenyglycine t-butyl ester (DAPT) (PE + D) group, (3) pIRES2 EGFP-Jagged1 (PEJ) group, and (4) PEJ combined DAPT (PEJ + D) group. Notch molecules were detected by real-time quantitative polymerase chain reaction or Western blotting. CD34, CD133, CD45, and KDR markers were detected by flow cytometry. EPC migration and proliferation were detected with a modified Boyden chamber and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, respectively; the tube formation ability was assayed by in vitro angiogenesis kit; EPC transfusion after Jagged1 gene transfection was performed in rat carotid artery injury models. Jagged1 gene transfection effectively activates notch-signaling pathway. Compared with PE groups, overexpression of Jagged1 significantly promoted AEPC functions including proliferation, migration, the tube formation ability, and cell differentiation, these effects could be reasonably diminished by DAPT. In vivo study demonstrated that Jagged1 overexpressing also significantly promoted AEPC homing to the vascular injury sites and decreases the neointima formation after vascular injury. Overexpression of Jagged1 ameliorates aged rat-derived EPC functions and increases its transfusion efficiency for balloon-induced rat arterial injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The endothelial border to health

    DEFF Research Database (Denmark)

    Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

    2017-01-01

    by hyperglycemic events because the endothelium transduces “high glucose” signaling into significant pathophysiological phenomena leading to reduced endothelial barrier function, compromised vascular tone regulation and inflammation (e.g., cytokine secretion and RAGE activation). In addition, endothelial...

  4. Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.

    Science.gov (United States)

    Zhao, Fei; Deng, Jiangshan; Yu, Xiaoyan; Li, Dawei; Shi, Hong; Zhao, Yuwu

    2015-08-01

    Hypoglycemia is a common and serious problem among patients with type 1 diabetes receiving treatment with insulin. Clinical studies have demonstrated that hypoglycemic edema is involved in the initiation of hypoglycemic brain damage. However, the mechanisms of this edema are poorly understood. Vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, has been observed an important candidate hormone induced by hypoglycemia to protect neurons by restoring plasma glucose. Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown. To investigate the effects of hypoglycemia on cerebral microvascular endothelial cells and assess the protective effect of exogenous VEGF on endothelial cells during hypoglycemia, confluent monolayers of the brain endothelial cell line bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM glucose) medium or hypoglycemic medium in the presence of VEGF. The results clearly showed that hypoglycemia significantly downregulated the expression of claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and distribution. Besides, transendothelial permeability significantly increased under hypoglycemic conditions compared to that under control conditions. Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial permeability via the inhibition of claudin-5 degradation and improved hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1) and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken together, hypoglycemia can significantly increase paraendocellular permeability by downregulating claudin-5 expression. We further showed that VEGF protected brain endothelial cells against hypoglycemia by enhancing glucose passage, reducing endothelial cell death, and ameliorating paraendocellular permeability.

  5. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan; Tan, Ren-Xiang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  6. Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.

    Science.gov (United States)

    Westphal, Sabine; Luley, Claus

    2011-09-01

    Consumption of flavanols improves chronic endothelial dysfunction. We investigated whether it can also improve acute lipemia-induced endothelial dysfunction. In this randomized, placebo-controlled, double-blind, crossover trial, 18 healthy subjects received a fatty meal with cocoa either rich in flavanols (918 mg) or flavanol-poor. Flow-mediated dilation (FMD), triglycerides, and free fatty acids were then determined over 6 h. After the flavanol-poor fat loading, the FMD deteriorated over 4 h. The consumption of flavanol-rich cocoa, in contrast, improved this deterioration in hours 2, 3, and 4 without abolishing it completely. Flavanols did not have any influence on triglycerides or on free fatty acids. Flavanol-rich cocoa can alleviate the lipemia-induced endothelial dysfunction, probably through an improvement in endothelial NO synthase.

  7. Improving GC-PPC-SAFT equation of state for LLE of hydrocarbons and oxygenated compounds with water

    DEFF Research Database (Denmark)

    Nguyen, Thanh-Binh; Jean-Charles, De Hemptinne; Creton, Benoit

    2014-01-01

    , uαβ, and wαβ are fitted on mutual solubilities of water and organic compounds. The regressed values which are obtained for each chemical family, are subsequently used for predicting infinite dilution activity coefficient in water and n-octanol/water partition coefficient.In general, the results......The GC-PPC-SAFT model has been shown to be useful for predicting the liquid-liquid phase split with water [Nguyen-Huynh et al. Ind. Eng. Chem. Res. 50 (2011) 7467-7483]. In order to extend the use of this model to oxygenated compounds for a large number of families (aliphatic ethers, aldehydes......, ketones, formates, acetates, propionates/butyrates, n-aliphatic acids), it is proposed to consider cross-association in addition to a binary interaction parameter lij on the combining rules for the cross-segment diameter between water and the investigated compound.The binary interaction parameters lij...

  8. Endothelial cells are essential for ovarian stromal tissue restructuring after xenotransplantation of isolated ovarian stromal cells

    National Research Council Canada - National Science Library

    Dath, C; Dethy, A; Van Langendonckt, A; Van Eyck, A S; Amorim, C A; Luyckx, V; Donnez, J; Dolmans, M M

    2011-01-01

    .... To help improve the grafting technique, we investigated whether short-term xenografting of a suspension containing ovarian stromal and endothelial cells without follicles could enhance graft survival...

  9. Short-Term Administration of Alibernet Red Wine Extract Failed To Affect Blood Pressure and To Improve Endothelial Function in Young Normotensive and Spontaneously Hypertensive Rats

    National Research Council Canada - National Science Library

    P Balis; A Púzserová; P Slezák; N Sestáková; O Pechánová; I Bernátová

    2013-01-01

      As wine polyphenols were shown to possess many positive effects in mammals, including improvement of vascular function, this study investigated the effect of the Slovak Alibernet red wine extract (AWE...

  10. Effects of Notch signalling pathway on the relationship between vascular endothelial dysfunction and endothelial stromal transformation in atherosclerosis.

    Science.gov (United States)

    Mao, Yong-Zhong; Jiang, Ling

    2017-06-16

    At present, with the improvement of living standards and population aging, the incidence of cardiovascular and cerebrovascular disease is on the rise and has been a serious threat to human health. Statistics show that the current death caused by cardiovascular and cerebrovascular disease has become the first cause of death has been increasing year by year. Therefore, studies on coronary heart disease and atherosclerosis (AS) have become a hot topic in clinical and basic research. In this study, the question of the effect of Notch signalling pathway on the relationship between endothelial dysfunction and endothelial stromal transformation in AS was studied in depth. Based on our results, we drew conclusions as follows. First, the Notch signalling pathway was activated in the atherosclerotic model; secondly, the Notch signalling pathway was demonstrated to enhance AS by promoting vascular endothelial dysfunction; thirdly, it was demonstrated that the Notch signalling pathway was mediated by promoting endothelial and to enhance AS; finally, we confirmed the endothelial function through the Notch signalling pathway to affect the transformation of endothelial stroma to achieve synergistic AS effect. The results of this study have a good guiding significance for the important role of Notch signalling in AS and indicate the ability to influence endothelial function and endothelial stromal transformation by intervening Notch signalling pathway and can affect the relationship between them, and thus eventually achieve the treatment of AS.

  11. Effects of N-acetyl-cysteine on endothelial function and inflammation in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    David J. Cohen

    2009-04-01

    Full Text Available Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flow-mediated vasodilation (FMD of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high-sensitivity C-reactive protein (CRP were measured at all four visits. At baseline, FMD was moderately impaired (3.7±2.9%. There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1±3.6% vs. 1.2±4.2%. Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04, while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross-over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation.

  12. Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

    Science.gov (United States)

    Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

    2016-02-01

    Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5

  13. Improved high-performance liquid chromatographic determination of guanidino compounds by precolumn dervatization with ninhydrin and fluorescence detection.

    Science.gov (United States)

    Buchberger, Wolfgang; Ferdig, Matthias

    2004-11-01

    Ninhydrin has been investigated as a pre-column derivatization reagent for guanidino compounds. The reaction takes place under strongly alkaline conditions, followed by a second step at low pH and elevated temperature. This procedure yields derivatives with favourable fluorescence properties (excitation at 390 nm, emission at 470 nm). Amino acids do not react with ninhydrin under these conditions so that the method can easily be used for biological samples. Reversed-phase HPLC separations of the derivatives of several representative guanidino compounds in human blood have been achieved with gradients consisting of aqueous formic acid and methanol. Fluorescence detection yields quantification limits of about 20 microg L(-1). Hyphenation with electrospray mass spectrometry has been used to confirm the identity of the derivatives.

  14. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Geferson Fischer

    2010-11-01

    Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

  15. Improving oxidative stability of echium oil emulsions fabricated by Microfluidics: Effect of ionic gelation and phenolic compounds.

    Science.gov (United States)

    Comunian, Talita A; Ravanfar, Raheleh; de Castro, Inar Alves; Dando, Robin; Favaro-Trindade, Carmen S; Abbaspourrad, Alireza

    2017-10-15

    Echium oil is rich in omega-3 fatty acids, which are important because of their benefits to human health; it is, however, unstable. The objective of this work was the coencapsulation of echium oil and quercetin or sinapic acid by microfluidic and ionic gelation techniques. The treatments were analyzed utilizing optical and scanning electron microscopy, encapsulation yield, particle size, thermogravimetry, Fourier transform infrared spectroscopy, stability under stress conditions, and oil oxidative/phenolic compound stability for 30days at 40°C. High encapsulation yield values were obtained (91-97% and 77-90% for the phenolic compounds and oil) and the encapsulated oil was almost seven times more stable than the non-encapsulated oil (0.34 vs 2.42mgMDA/kg oil for encapsulated and non-encapsulated oil, respectively). Encapsulation was shown to promote oxidative stability, allowing new vehicles for the application of these compounds in food without the use of solvents and high temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T

    2012-01-01

    through cleavage of big ET1 by endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). METHOD: We investigated whether the dual NEP/ECE inhibitor SOL1 improves resistance artery function and structure in 12 weeks old spontaneously hypertensive rats (SHRs) and whether arterial structural...

  17. Nanomedicines for Endothelial Disorders

    OpenAIRE

    Chung, Bomy Lee; Toth, Michael J.; Kamaly, Nazila; Sei, Yoshitaka J.; Becraft, Jacob; Mulder, Willem J. M.; Fayad, Zahi A; Farokhzad, Omid C.; Kim, YongTae; Langer, Robert

    2015-01-01

    The endothelium lines the internal surfaces of blood and lymphatic vessels and has a critical role in maintaining homeostasis. Endothelial dysfunction is involved in the pathology of many diseases and conditions, including disorders such as diabetes, cardiovascular diseases, and cancer. Given this common etiology in a range of diseases, medicines targeting an impaired endothelium can strengthen the arsenal of therapeutics. Nanomedicine – the application of nanotechnology to healthcare – prese...

  18. Lonidamine Causes Inhibition of Angiogenesis-Related Endothelial Cell Functions

    Directory of Open Access Journals (Sweden)

    Donatella Del Bufalo

    2004-09-01

    Full Text Available The aim of this study was to assess whether lonidamine (LND interferes with some steps in angiogenesis progression. We report here, for the first time, that LND inhibited angiogenic-related endothelial cell functions in a dose-dependent manner (1-50 μg/ml. In particular, LND decreased proliferation, migration, invasion, and morphogenesis on matrigel of different endothelial cell lines. Zymographic and Western blot analysis assays showed that LND treatment produced a reduction in the secretion of matrix metalloproteinase-2 and metalloproteinase-9 by endothelial cells. Vessel formation in a matrigel plug was also reduced by LND. The viability, migration, invasion, and matrix metalloproteinase production of different tumor cell lines were not affected by low doses of LND (1-10 μg/ml, whereas 50 μg/ml LND, which corresponds to the dose used in clinical management of tumors, triggered apoptosis both in endothelial and tumor cells. Together, these data demonstrate that LND is a compound that interferes with endothelial cell functions, both at low and high doses. Thus, the effect of LND on endothelial cell functions, previously undescribed, may be a significant contributor to the antitumor effect of LND observed for clinical management of solid tumors.

  19. Human iPSC-Derived Endothelial Cell Sprouting Assay in ...

    Science.gov (United States)

    Activation of vascular endothelial cells (ECs) by growth factors initiates a cascade of events in vivo consisting of EC tip cell selection, sprout formation, EC stalk cell proliferation, and ultimately vascular stabilization by support cells. Although EC functional assays can recapitulate one or more aspects of angiogenesis in vitro, they are often limited by a lack of definition to the substratum and lack of dependence on key angiogenic signaling axes. Here, we designed and characterized a chemically-defined model of endothelial sprouting behavior in vitro using human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs). Thiol-ene photopolymerization was used to rapidly encapsulate iPSC-ECs at high density in poly(ethylene glycol) (PEG) hydrogel spheres and subsequently to rapidly encapsulate iPSC-EC-containing hydrogel spheres in a cell-free over-layer. The hydrogel sprouting array here maintained pro-angiogenic phenotype of iPSC-ECs and supported growth factor-dependent proliferation and sprouting behavior. The sprouting model responded appropriately to several reference pharmacological angiogenesis inhibitors, which suggests the functional role of vascular endothelial growth factor, NF-κB, matrix metalloproteinase-2/9, protein kinase activity, and β-tubulin in endothelial sprouting. A blinded screen of 38 putative vascular disrupting compounds (pVDCs) from the US Environmental Protection Agency’s ToxCast library identified five compounds th

  20. Validation of determination of plasma metabolites derived from thyme bioactive compounds by improved liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Rubió, Laura; Serra, Aida; Macià, Alba; Borràs, Xenia; Romero, Maria-Paz; Motilva, Maria-José

    2012-09-15

    In the present study, a selective and sensitive method, based on microelution solid-phase extraction (μSPE) plate and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was validated and applied to determine the plasma metabolites of the bioactive compounds of thyme. For validation process, standards of the more representative components of the phenolic and monoterpene fractions of thyme were spiked in plasma samples and then the quality parameters of the method were studied. Extraction recoveries (%R) of the studied compounds were higher than 75%, and the matrix effect (%ME) was lower than 18%. The LODs ranged from 1 to 65 μg/L, except for the thymol sulfate metabolite, which was 240 μg/L. This method was then applied for the analysis of rat plasma obtained at different times, from 0 to 6h, after an acute intake of thyme extract (5 g/kg body weight). Different thyme metabolites were identified and were mainly derived from rosmarinic acid (coumaric acid sulfate, caffeic acid sulfate, ferulic acid sulfate, hydroxyphenylpropionic acid sulfate, dihydroxyphenylpropionic acid sulfate and hydroxybenzoic acid) and thymol (thymol sulfate and thymol glucuronide). The most abundant thyme metabolites generated were hydroxyphenylpropionic acid sulfate and thymol sulfate, their respective concentrations in plasma being 446 and 8464 μM 1h after the intake of the thyme extract. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Improving the On-Line Extraction of Polar Compounds by IT-SPME with Silica Nanoparticles Modified Phases

    Directory of Open Access Journals (Sweden)

    Pascual Serra-Mora

    2018-02-01

    Full Text Available In the present work the extraction efficiency of in-tube solid-phase microextraction (IT-SPME for polar herbicides has been evaluated using extractive capillaries coated with different polymeric sorbents. For this purpose, aqueous solutions of herbicides with a wide range of polarities, including some highly polar compounds (log Kow < 1, have been directly processed by IT-SPME coupled on-line to capillary liquid chromatography with UV-diode array detection. For extraction, commercially available capillary columns coated with polydimethylsiloxane (PDMS and polyetilenglicol (PEG-based phases have been used, and the results have been compared with those obtained with a synthesized tetraethyl orthosilicate (TEOS-trimethoxyethylsilane (MTEOS polymer, as well as the same polymer reinforced with silica nanoparticles (SiO2 NPs. The SiO2 NPs functionalized TEOS-MTEOS coating provided the best results for most herbicides, especially for the most polar compounds. On the basis of the results obtained, conditions for the quantification of the herbicides tested are described using a SiO2 NPs reinforced TEOS-MTEOS coated capillary. The proposed method provided satisfactory linearity up to concentrations of 200 μg/L. The precision was also suitable, with relative standard deviations (RSDs values ≤9% (n = 3, and the limits of detection (LODs were within the 0.5–7.5 µg/L range. The method has been applied to different water samples and the extract obtained from an agricultural soil.

  2. Towards improving sterile insect technique: Exposure to orange oil compounds increases sexual signalling and longevity in Ceratitis capitata males of the Vienna 8 GSS

    Science.gov (United States)

    Gerofotis, Christos D.; Ioannou, Charalampos S.; Iliadis, Ioannis V.; Papadopoulos, Nikos T.; Koveos, Dimitris S.

    2017-01-01

    The Mediterranean fruit fly (medfly), Ceratitis capitata, is a notorious insect pest causing huge economic losses worldwide. The sterile insect technique (SIT) is widely used for its control. Using sexually mature sterilized males of the Vienna 8 (tsl) strain in the laboratory, we explored whether exposure of males to citrus compounds (separately or in a mixture) affects their sexual behaviour and if nutritional conditions and age modulate those effects. Exposed males exhibited increased sexual signalling compared to unexposed ones, particularly when fed a rich adult diet. Interestingly, and for the first time reported in medfly, exposure of Vienna 8 males to a mixture of citrus compounds increases longevity under poor adult diet conditions. We discuss the possible associated mechanisms and provide some practical implications of our results towards improving the effectiveness of SIT. PMID:29190755

  3. Towards improving sterile insect technique: Exposure to orange oil compounds increases sexual signalling and longevity in Ceratitis capitata males of the Vienna 8 GSS.

    Directory of Open Access Journals (Sweden)

    Nikos A Kouloussis

    Full Text Available The Mediterranean fruit fly (medfly, Ceratitis capitata, is a notorious insect pest causing huge economic losses worldwide. The sterile insect technique (SIT is widely used for its control. Using sexually mature sterilized males of the Vienna 8 (tsl strain in the laboratory, we explored whether exposure of males to citrus compounds (separately or in a mixture affects their sexual behaviour and if nutritional conditions and age modulate those effects. Exposed males exhibited increased sexual signalling compared to unexposed ones, particularly when fed a rich adult diet. Interestingly, and for the first time reported in medfly, exposure of Vienna 8 males to a mixture of citrus compounds increases longevity under poor adult diet conditions. We discuss the possible associated mechanisms and provide some practical implications of our results towards improving the effectiveness of SIT.

  4. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  5. A role for diallyl trisulfide in mitochondrial antioxidative stress contributes to its protective effects against vascular endothelial impairment.

    Science.gov (United States)

    Liu, Li-Li; Yan, Li; Chen, Yuan-Hong; Zeng, Guo-Hua; Zhou, Ying; Chen, He-Ping; Peng, Wei-Jie; He, Ming; Huang, Qi-Ren

    2014-02-15

    Persistent hyperglycemia increases a systemic oxidative stress, causing the onset of vascular endothelial dysfunction and atherosclerosis. Diallyl trisulfide (DAT), a natural organosulfur compound in garlic, has been reported to have actions of dilating blood vessels and antibacteria, etc. In this study, models of obese diabetic rat in vivo and high glucose concentration (HG)-induced endothelial cell injury in vitro were used to investigate the protective effects of DAT on vascular endothelial injury and its underlying mechanisms. In the in vivo model, the obese diabetic rats were injected venously with DAT (5.0 mg kg(-1)d(-1)) and Vitamin E (1.0 mg kg(-1)d(-1)) respectively, once daily for 7 consecutive days. In the in vitro model, HG-injured HUVEC were treated with or without DAT (25 µmol L(-1), 50 µmol L(-1), 100 µmol L(-1)) or Vitamin E (25 µmol L(-1)) respectively for 24h. The extents of vascular endothelial injury and protective effects of DAT were evaluated. The results both in vivo and in vitro displayed that DAT-treatment significantly attenuated the endothelial cell impairments. Besides, DAT-treatment markedly decreased the levels of malondialdehyde (MDA) and reactive oxygen species, whereas elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondrium. Moreover, DAT-treatment considerably improved mitochondrial respiration function. Taken together, our results suggest that DAT protects vascular endothelium from HG or hyperglycemia induced-injury by reducing mitochondrial oxidative stress. The findings provide a novel insight for DAT to potentially treat the oxidative stress diseases, i.e., atherosclerosis, diabetes, and neurodegenerative diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. An improved high performance liquid chromatography-fluorescence detection method for the analysis of major phenolic compounds in cigarette smoke and smokeless tobacco products.

    Science.gov (United States)

    Wu, Jingcun; Rickert, William S; Masters, Andrew

    2012-11-16

    An improved HPLC method has been developed for the determination of major phenolic compounds in cigarette smoke. A novel reversed phase column with a pentafluorophenylpropyl (PFP) ligand in the stationary phase was chosen to separate the positional isomers (p-, m-, and o-cresols). Methanol instead of acetonitrile was used as the organic mobile phase component to improve the separation of the isomers and cope with the crisis of global acetonitrile shortage in 2009. A shorter analytical column with smaller particle size was used to further increase separation efficiency and reduces solvent consumption. These improvements have led to a new HPLC method that is simpler and faster than the GC-MS method and more sensitive, selective and efficient than the widely used traditional HPLC method. The limit of detection (LOD) and limit of quantification (LOQ) of this method are at the ng/mL level for most of the phenols with good linearity (R(2) ≥ 0.999) and precision (RSDcigarette smoke yields of phenolic compounds obtained by this method are comparable to those obtained by traditional HPLC method with the advantage that p-, m-, and o-cresols can be determined and reported separately by the new method. The method can also be applied for analysis of phenols in smokeless tobacco product. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Magnetizable stent-grafts enable endothelial cell capture

    Energy Technology Data Exchange (ETDEWEB)

    Tefft, Brandon J. [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Uthamaraj, Susheil [Division of Engineering, Mayo Clinic, Rochester, MN (United States); Harburn, J. Jonathan [School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees (United Kingdom); Hlinomaz, Ota [Department of Cardioangiology, St. Anne' s University Hospital, Brno (Czech Republic); Lerman, Amir [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Dragomir-Daescu, Dan [Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN (United States); Sandhu, Gurpreet S., E-mail: sandhu.gurpreet@mayo.edu [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States)

    2017-04-01

    Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance. - Highlights: • Magnetic stent-grafts were made from 2205 steel stents and polyurethane nanofibers. • Stent-grafts remained patent and formed a thin and uniform neointima when implanted. • Stent-grafts captured endothelial cells labeled with magnetic nanoparticles.

  8. In Vitro Endothelialization Test of Biomaterials Using Immortalized Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Ken Kono

    Full Text Available Functionalizing biomaterials with peptides or polymers that enhance recruitment of endothelial cells (ECs can reduce blood coagulation and thrombosis. To assess endothelialization of materials in vitro, primary ECs are generally used, although the characteristics of these cells vary among the donors and change with time in culture. Recently, primary cell lines immortalized by transduction of simian vacuolating virus 40 large T antigen or human telomerase reverse transcriptase have been developed. To determine whether immortalized ECs can substitute for primary ECs in material testing, we investigated endothelialization on biocompatible polymers using three lots of primary human umbilical vein endothelial cells (HUVEC and immortalized microvascular ECs, TIME-GFP. Attachment to and growth on polymer surfaces were comparable between cell types, but results were more consistent with TIME-GFP. Our findings indicate that TIME-GFP is more suitable for in vitro endothelialization testing of biomaterials.

  9. Endothelial RIG-I activation impairs endothelial function.

    Science.gov (United States)

    Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2012-03-30

    Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5'end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: role of NADPH oxidase.

    Science.gov (United States)

    López-Sepúlveda, Rocío; Gómez-Guzmán, Manuel; Zarzuelo, Maria José; Romero, Miguel; Sánchez, Manuel; Quintela, Ana María; Galindo, Pilar; O'Valle, Francisco; Tamargo, Juan; Pérez-Vizcaíno, Francisco; Duarte, Juan; Jiménez, Rosario

    2011-04-01

    RWPs (red wine polyphenols) exert antihypertensive effects and improve endothelial function by reducing the plasma levels of ET-1 (endothelin-1) and the subsequent vascular production of O(2)(•-) (superoxide anion). Our present study was designed to evaluate whether RWPs act directly in the vascular wall improving endothelial dysfunction and O(2)(•-) production induced by ET-1 and to analyse the compounds responsible for these protective effects. We incubated rat isolated aortic rings in the presence or absence of ET-1 (10 nM) and RWPs (10(-4) to 10(-2) g/l) or catechin (0.2 μM), epicatechin (10 μM) and resveratrol (0.1 μM). ET-1 reduced the relaxant responses to acetylcholine, increased intracellular O(2)(•-) production, NADPH oxidase activity and protein expression of NADPH oxidase subunit p47phox. All these changes were prevented by RWPs. The preventive effects of RWPs were unaffected by co-incubation with either ICI-182780, an ER (oestrogen receptor) antagonist, or GW9662, a PPARγ (peroxisome-proliferator-activated receptor γ) antagonist. RWPs inhibited the phosphorylation of the mitogen-activated protein kinase, ERK1/2 (extracellular signal-regulated kinase 1/2), a key regulator of p47phox expression in response to ET-1. When the isolated polyphenols were tested, at the concentrations found in 10(-2) g/l RWPs, only epicatechin prevented endothelial dysfunction and all biochemical changes induced by ET-1 in the vascular wall. Taken together, these results indicate that RWPs prevent ET-1-induced vascular O(2)(•-) production by reducing overexpression of p47phox and the subsequent increased NADPH oxidase activity, leading to improvement in endothelial function. The effects of RWPs appear to be independent of ER and PPARγ activation and are related to ERK1/2 inhibition.

  11. A novel approach to emission modelling of biogenic volatile organic compounds in Europe: improved seasonality and land-cover

    Science.gov (United States)

    Oderbolz, D. C.; Aksoyoglu, S.; Keller, J.; Barmpadimos, I.; Steinbrecher, R.; Skjøth, C. A.; Plaß-Dülmer, C.; Prévôt, A. S. H.

    2012-08-01

    Biogenic volatile organic compounds (BVOC) emitted from vegetation are important for the formation of secondary pollutants such as ozone and secondary organic aerosols (SOA) in the atmosphere. Therefore, BVOC emission are an important input for air quality models. To model these emissions with high spatial resolution, the accuracy of the underlying vegetation inventory is crucial. We present a BVOC emission model that accommodates different vegetation inventories and uses satellite-based measurements of greenness instead of pre-defined vegetation periods. This approach to seasonality implicitly treats effects caused by water or nutrient availability, altitude and latitude on a plant stand. Additionally, we test the influence of proposed seasonal variability in enzyme activity on BVOC emissions. In its present setup, the emission model calculates hourly emissions of isoprene, monoterpenes, sesquiterpenes and the oxygenated volatile organic compounds (OVOC) methanol, formaldehyde, formic acid, ethanol, acetaldehyde, acetone and acetic acid. In this study, emissions based on three different vegetation inventories are compared with each other and diurnal and seasonal variations in Europe are investigated for the year 2006. Two of these vegetation inventories require information on tree-cover as an input. We compare three different land-cover inventories (USGS GLCC, GLC2000 and Globcover 2.2) with respect to tree-cover. The often-used USGS GLCC land-cover inventory leads to a severe reduction of BVOC emissions due to a potential miss-attribution of broad-leaved trees and reduced tree-cover compared to the two other land-cover inventories. To account for uncertainties in the land-cover classification, we introduce land-cover correction factors for each relevant land-use category to adjust the tree-cover. The results are very sensitive to these factors within the plausible range. For June 2006, total monthly BVOC emissions decreased up to -27% with minimal and increased

  12. A comprehensive emission inventory of biogenic volatile organic compounds in Europe: improved seasonality and land-cover

    Science.gov (United States)

    Oderbolz, D. C.; Aksoyoglu, S.; Keller, J.; Barmpadimos, I.; Steinbrecher, R.; Skjøth, C. A.; Plaß-Dülmer, C.; Prévôt, A. S. H.

    2013-02-01

    Biogenic volatile organic compounds (BVOC) emitted from vegetation are important for the formation of secondary pollutants such as ozone and secondary organic aerosols (SOA) in the atmosphere. Therefore, BVOC emission are an important input for air quality models. To model these emissions with high spatial resolution, the accuracy of the underlying vegetation inventory is crucial. We present a BVOC emission model that accommodates different vegetation inventories and uses satellite-based measurements of greenness instead of pre-defined vegetation periods. This approach to seasonality implicitly treats effects caused by water or nutrient availability, altitude and latitude on a plant stand. Additionally, we test the influence of proposed seasonal variability in enzyme activity on BVOC emissions. In its present setup, the emission model calculates hourly emissions of isoprene, monoterpenes, sesquiterpenes and the oxygenated volatile organic compounds (OVOC) methanol, formaldehyde, formic acid, ethanol, acetaldehyde, acetone and acetic acid. In this study, emissions based on three different vegetation inventories are compared with each other and diurnal and seasonal variations in Europe are investigated for the year 2006. Two of these vegetation inventories require information on tree-cover as an input. We compare three different land-cover inventories (USGS GLCC, GLC2000 and Globcover 2.2) with respect to tree-cover. The often-used USGS GLCC land-cover inventory leads to a severe reduction of BVOC emissions due to a potential miss-attribution of broad-leaved trees and reduced tree-cover compared to the two other land-cover inventories. To account for uncertainties in the land-cover classification, we introduce land-cover correction factors for each relevant land-use category to adjust the tree-cover. The results are very sensitive to these factors within the plausible range. For June 2006, total monthly BVOC emissions decreased up to -27% with minimal and increased

  13. A comprehensive emission inventory of biogenic volatile organic compounds in Europe: improved seasonality and land-cover

    Directory of Open Access Journals (Sweden)

    D. C. Oderbolz

    2013-02-01

    Full Text Available Biogenic volatile organic compounds (BVOC emitted from vegetation are important for the formation of secondary pollutants such as ozone and secondary organic aerosols (SOA in the atmosphere. Therefore, BVOC emission are an important input for air quality models. To model these emissions with high spatial resolution, the accuracy of the underlying vegetation inventory is crucial. We present a BVOC emission model that accommodates different vegetation inventories and uses satellite-based measurements of greenness instead of pre-defined vegetation periods. This approach to seasonality implicitly treats effects caused by water or nutrient availability, altitude and latitude on a plant stand. Additionally, we test the influence of proposed seasonal variability in enzyme activity on BVOC emissions. In its present setup, the emission model calculates hourly emissions of isoprene, monoterpenes, sesquiterpenes and the oxygenated volatile organic compounds (OVOC methanol, formaldehyde, formic acid, ethanol, acetaldehyde, acetone and acetic acid. In this study, emissions based on three different vegetation inventories are compared with each other and diurnal and seasonal variations in Europe are investigated for the year 2006. Two of these vegetation inventories require information on tree-cover as an input. We compare three different land-cover inventories (USGS GLCC, GLC2000 and Globcover 2.2 with respect to tree-cover. The often-used USGS GLCC land-cover inventory leads to a severe reduction of BVOC emissions due to a potential miss-attribution of broad-leaved trees and reduced tree-cover compared to the two other land-cover inventories. To account for uncertainties in the land-cover classification, we introduce land-cover correction factors for each relevant land-use category to adjust the tree-cover. The results are very sensitive to these factors within the plausible range. For June 2006, total monthly BVOC emissions decreased up to −27% with

  14. Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

    Science.gov (United States)

    Gonzalez, Eric J.; Merrill, Liana

    2014-01-01

    Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

  15. Initial results of small incision deep lamellar endothelial keratoplasty (DLEK).

    Science.gov (United States)

    Fogla, Rajesh; Padmanabhan, Prema

    2006-02-01

    To evaluate the results of replacing the posterior stroma and endothelium, using small incision deep lamellar endothelial keratoplasty (DLEK) surgical technique, in patients with corneal endothelial dysfunction. Noncomparative case series. Fifteen eyes of 15 patients (six males and nine females) with endothelial dysfunction were included in this study. Through a 5-mm scleral incision, a deep lamellar pocket was created across the cornea, followed by excision of an 8.0-mm disk of posterior lamellar corneal tissue. Same size lamellar donor disk was prepared and placed in position without the need of suture fixation. Best spectacle-corrected visual acuity (BSCVA), refraction, endothelial cell density, corneal topography, and corneal thickness were analyzed. Average BSCVA preoperative was 20/200 (range 20/40 to hand movements (HM)), improving to 20/50 (range 20/20 to 20/120) at a mean follow-up of 7.2 months. Average refractive astigmatism at last follow-up was 1.46+/-1.21 diopters (range, 0 to 4 diopters). Preoperative average donor endothelial cell density was 2047+/-311 cells/mm2, and that at last follow-up was 1732+/-514 cells/mm2. Preoperative average pachymetry was 801.4+/-211.3 microm, improving to 553+/-90.4 microm at last follow-up. Initial results with small incision DLEK procedure indicate that it is a safe procedure that provides healthy donor endothelial cell count and function postoperatively, with encouraging visual results.

  16. [Medical significance of endothelial glycocalyx].

    Science.gov (United States)

    Frati-Munari, Alberto C

    2013-01-01

    Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. It has several physiological roles: shear stress mechanotransduction to the endothelial cells, regulation of fluids and macromolecules vascular permeability, of coagulation cascade activation and fibrinolysis, and protects the endothelium from platelets and leukocytes adhesion. In general, glycocalyx protects vascular wall against pathogenic insults. The glycocalyx may be damaged by abnormal shear stress, reactive oxygen species, hypernatremia, hyperglycemia, hypercholesterolemia and inflammatory molecules, resulting in endothelial dysfunction, enhanced vascular permeability, lipoproteins leakage to subendothelial space, activation of plasma coagulation, and increased adherence of platelets and leukocytes to the endothelial cells. Shredding of glycocalyx appears as an important initial step in the pathophysiology of vascular diseases. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  17. Improvement of selenium determination in water by inductively coupled plasma mass spectrometry through use of organic compounds as matrix modifiers

    Science.gov (United States)

    Llorente, I.; Gómez, M.; Cámara, C.

    1997-10-01

    The effect of organic modifiers such as monofunctional alcohols, polyalcohols and organic acids on selenium response intensity and on polyatomic interferences by inductively coupled plasma-mass spectrometry (ICP-MS) has been evaluated and the possible mechanisms discussed. It has been proved that the addition of small amounts (sugar, ethylene glycol and tartaric acid, in combination with instrumental adjustments, significantly improves the Se/polyatomic interference signal ratio. The 40Ar 37Cl + interference is significantly alleviated by addition of 4% lactic acid or 4% glycerol, the Se/ArCl ratio with the latter being even higher than in the absence of chloride. Se sensitivity and detection limits are improved about two-to six-fold by addition of the appropriate modifier and selecting the optimum working conditions. The proposed methods for Se determination in environmental samples, even those containing high chloride concentrations, are very promising and have been applied to some certified samples.

  18. Volatile Compound Profiling by HS-SPME/GC-MS-FID of a Core Olive Cultivar Collection as a Tool for Aroma Improvement of Virgin Olive Oil

    Directory of Open Access Journals (Sweden)

    Lourdes García-Vico

    2017-01-01

    Full Text Available Virgin olive oil (VOO is the only food product requiring official sensory analysis to be classified in commercial categories, in which the evaluation of the aroma plays a very important role. The selection of parents, with the aim of obtaining new cultivars with improved oil aroma, is of paramount importance in olive breeding programs. We have assessed the volatile fraction by headspace-solid-phase microextraction/gas chromatography-mass spectrometry-flame ionization detection (HS-SPME/GC-MS-FID and the deduced aroma properties of VOO from a core set of olive cultivars (Core-36 which possesses most of the genetic diversity found in the World Olive Germplasm Collection (IFAPA Alameda del Obispo located in Cordoba, Spain. The VOO volatile fractions of Core-36 cultivars display a high level of variability. It is mostly made of compounds produced from polyunsaturated fatty acids through the lipoxygenase pathway, which confirms to be a general characteristic of the olive species (Olea europaea L.. The main group of volatile compounds in the oils was six straight-chain carbon compounds derived from linolenic acid, some of them being the main contributors to the aroma of the olive oils according to their odor activity values (OAV. The high level of variability found for the volatile fraction of the oils from Core-36 and, therefore, for the aroma odor notes, suggest that this core set may be a very useful tool for the choice of optimal parents in olive breeding programs in order to raise new cultivars with improved VOO aroma.

  19. Volatile Compound Profiling by HS-SPME/GC-MS-FID of a Core Olive Cultivar Collection as a Tool for Aroma Improvement of Virgin Olive Oil.

    Science.gov (United States)

    García-Vico, Lourdes; Belaj, Angjelina; Sánchez-Ortiz, Araceli; Martínez-Rivas, José M; Pérez, Ana G; Sanz, Carlos

    2017-01-14

    Virgin olive oil (VOO) is the only food product requiring official sensory analysis to be classified in commercial categories, in which the evaluation of the aroma plays a very important role. The selection of parents, with the aim of obtaining new cultivars with improved oil aroma, is of paramount importance in olive breeding programs. We have assessed the volatile fraction by headspace-solid-phase microextraction/gas chromatography-mass spectrometry-flame ionization detection (HS-SPME/GC-MS-FID) and the deduced aroma properties of VOO from a core set of olive cultivars (Core-36) which possesses most of the genetic diversity found in the World Olive Germplasm Collection (IFAPA Alameda del Obispo) located in Cordoba, Spain. The VOO volatile fractions of Core-36 cultivars display a high level of variability. It is mostly made of compounds produced from polyunsaturated fatty acids through the lipoxygenase pathway, which confirms to be a general characteristic of the olive species (Olea europaea L.). The main group of volatile compounds in the oils was six straight-chain carbon compounds derived from linolenic acid, some of them being the main contributors to the aroma of the olive oils according to their odor activity values (OAV). The high level of variability found for the volatile fraction of the oils from Core-36 and, therefore, for the aroma odor notes, suggest that this core set may be a very useful tool for the choice of optimal parents in olive breeding programs in order to raise new cultivars with improved VOO aroma.

  20. Lactic Acid Fermentation Improved Textural Behaviour, Phenolic Compounds and Antioxidant Activity of Chia 
(Salvia hispanica L.) Dough.

    Science.gov (United States)

    Bustos, Ana Yanina; Gerez, Carla Luciana; Mohtar Mohtar, Lina Goumana; Paz Zanini, Verónica Irene; Nazareno, Mónica Azucena; Taranto, María Pía; Iturriaga, Laura Beatriz

    2017-09-01

    In this work, autochthonous lactic acid bacteria (LAB) were isolated from chia (Salvia hispanica L.) dough and selected on the basis of the kinetics of acidification and proteolytic activity. Strain no. C8, identified as Lactobacillus plantarum C8, was selected and used as starter to obtain chia sourdough. Lactic acid fermentation increased the organic acid mass fractions (lactic, acetic and phenyl lactic acids to 12.3 g, 1.0 g and 23.8 µg per kg of dough respectively), and antioxidant activities, which increased by approx. 33-40% compared to unfermented chia flour dough. In addition, total phenolic content increased 25% and its composition was strongly modified after 24 h of fermentation by L. plantarum C8. Chlorogenic acid was only found in the fermented dough (2.5 mg/g), while ferulic acid was detected from the beginning of fermentation, being 32% higher in chia sourdough (5.6 mg/g). The use of fermented chia sourdough improved the overall characteristics of white bread, including physical (e.g. reduced hardness and chewiness of the crumb) and antioxidant properties (25% on average), compared to the white bread. These results indicate that the use of chia sourdough could be a promising alternative to improve the technological and antioxidant properties of wheat bread. In addition, this work has shown, for the first time, that lactic acid bacterium is able to ferment chia dough, improving its overall characteristics.

  1. Lactic Acid Fermentation Improved Textural Behaviour, Phenolic Compounds and Antioxidant Activity of Chia (Salvia hispanica L. Dough

    Directory of Open Access Journals (Sweden)

    Ana Yanina Bustos

    2017-01-01

    Full Text Available In this work, autochthonous lactic acid bacteria (LAB were isolated from chia (Salvia hispanica L. dough and selected on the basis of the kinetics of acidifi cation and proteolytic activity. Strain no. C8, identifi ed as Lactobacillus plantarum C8, was selected and used as starte r to obtain chia sourdough. Lactic acid fermentation increased the organic acid mass fractions (lactic, acetic and phenyl lactic acids to 12.3 g, 1.0 g and 23.8 μg per kg of dough respectively, and antioxidant activities, which increased by approx. 33–40 % compared to unfermented chia fl our dough. In addition, total phenolic content increased 25 % and its composition was strongly modifi ed aft er 24 h of fermentation by L. plantarum C8. Chlorogenic acid was only found in the fermented dough (2.5 mg/g, while ferulic acid was detected from the beginning of fermentation, being 32 % higher in chia sourdough (5.6 mg/g. The use of fermented chia sourdough improved the overall characteristics of white bread, including physical (e.g. reduced hardness and chewiness of the crumb and antioxidant properties (25 % on average, compared to the white bread. These results indicate that the use of chia sourdough could be a promising alternative to improve the technological and antioxidant properties of wheat bread. In addition, this work has shown, for the fi rst time, that lactic acid bacterium is able to ferment chia dough, improving its overall characteristics.

  2. Improvement of a headspace solid phase microextraction-gas chromatography/mass spectrometry method for the analysis of wheat bread volatile compounds.

    Science.gov (United States)

    Raffo, Antonio; Carcea, Marina; Castagna, Claudia; Magrì, Andrea

    2015-08-07

    An improved method based on headspace solid phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME/GC-MS) was proposed for the semi-quantitative determination of wheat bread volatile compounds isolated from both whole slice and crust samples. A DVB/CAR/PDMS fibre was used to extract volatiles from the headspace of a bread powdered sample dispersed in a sodium chloride (20%) aqueous solution and kept for 60min at 50°C under controlled stirring. Thirty-nine out of all the extracted volatiles were fully identified, whereas for 95 other volatiles a tentative identification was proposed, to give a complete as possible profile of wheat bread volatile compounds. The use of an array of ten structurally and physicochemically similar internal standards allowed to markedly improve method precision with respect to previous HS-SPME/GC-MS methods for bread volatiles. Good linearity of the method was verified for a selection of volatiles from several chemical groups by calibration with matrix-matched extraction solutions. This simple, rapid, precise and sensitive method could represent a valuable tool to obtain semi-quantitative information when investigating the influence of technological factors on volatiles formation in wheat bread and other bakery products. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. EFFECT OF HIGH-INTENSITY EXERCISE ON ENDOTHELIAL FUNCTION IN PATIENTS WITH T2DM

    OpenAIRE

    Silva, Carlos Alberto da; Lopes Vasconcelos-Filho, Francisco Sérgio; Serafim, Marcus; Botura, Edson; Rocha-e-Silva, Roberta Cristina da; Pacheco, Christina; Marques, Fernando Antônio Oliveira; Melo, Sebastião Iberes Lopes

    2016-01-01

    Introduction: Diabetes mellitus is the most common metabolic disease worldwide. Endothelial dysfunction characteristic of these patients is one of the major risk factors for atherosclerosis. Early diagnosis of endothelial dysfunction is essential for the treatment especially of non-invasive manner, such as flow mediated dilation. Physical exercise is capable of generating beneficial adaptations may improve endothelial function. Objective: Identify the effect of physical exercise, using the...

  4. Improvement of physicochemical properties and phenolic compounds bioavailability by concentrating dietary fiber of peach (Prunus persica) juice by-product.

    Science.gov (United States)

    Rodríguez-González, Sarahí; Pérez-Ramírez, Iza F; Castaño-Tostado, Eduardo; Amaya-Llano, Silvia; Rodríguez-García, Mario E; Reynoso-Camacho, Rosalía

    2017-12-06

    This study aimed to concentrate dietary fiber (DF) from peach (Prunus persica) juice by-product (PJBP), to improve its functional properties, and its polyphenols bioavailability. The dietary fiber concentrates (DFC) were obtained from PJBP using water/ethanol treatments (100:0, 20:80, 50:50, 80:20, and 0:100, v/v) at 1:5 ratio (wet weight/solvent, w/v) for 5 and 20 min at 21 °C. All treatments concentrated condensed tannins, total and insoluble DF, founding the highest content with 100% H2O treatment. The major polyphenols of DFC were 4-O-caffeoylquinic, chlorogenic, and 1,5-Di-O-caffeoylquinic acids. Water and oil retention capacity and maximum glucose diffusion rate were improved mainly with 100% H2O treatment. Healthy rats were fed with standard diet supplemented with 8% of PJBP, DFC obtained with 100% H2O for 5 min, or DFC obtained with 20% EtOH for 5 min. Gastrointestinal digesta weight and viscosity were increased in animals supplemented with 100% H2O DFC. Moreover, the urinary excretion of polyphenol metabolites, mainly glucuronide and sulfate conjugates, was increased with this treatment, indicating a greater bioavailability of PJBP polyphenols, which was associated with an increased dietary fiber porosity. Water treatment could be used to potentiate PJBP functional properties and polyphenols bioavailability. This article is protected by copyright. All rights reserved.

  5. Observational study: daily treatment with a new compound “tradamixina” plus serenoa repens for two months improved the lower urinary tract symptoms

    Science.gov (United States)

    2012-01-01

    Background Lower urinary tract symptoms (LUTS) are associated with great emotional costs to individuals and substantial economic costs to society. This study seeks to evaluate the effect of a new natural compound “Tradamixina plus Serenoa Repens” in order to improve lower urinary tract symptoms. Methods 100 patients (≥45years) who had had LUTS/BPH for >6 mo at screening and with IPSS -The international Prostate symptom scores- ≥13 and maximum urinary flow rate (Qmax) ≥4 to ≤15 ml/s. were recruited. The compound “Tradamixina plus Serenoa Repens” (80 mg of Alga Ecklonia Bicyclis, 100 mg of Tribulus Terrestris and 100 mg of D-Glucosamine and N-Acetyl-D-Glucosamine plus 320 mg of Serenoa Repens) was administered daily for 2 months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical urological history, clinical examination, laboratory investigations (total PSA), and instrumental examination like urolfowmetry. Efficacy measures included IPSS-International Prostate Sympto, BPH Impact Index (BII), Quality-of-Life (QoL) Index. Measures were assessed at baseline and end point (12 wk or end of therapy) and also at screening, 1 and 4 wk for IPSS, and 4 wk for BII. Statistical significance was interpreted only if the results of the preceding analysis were significant at the 0.05 level. Results After 2 months of treatment the change from baseline to week 12 relative to “Tradamixina plus Seronea Repens” in total IPSS and Qol was statistically significant. Differences from baseline in BII were statistically significant for “Tradamixina plus Seronea Repens” above all differences in BII were also significant at 4 wk (LSmean ± SE: -0.8 ± 0.2). In the distribution of subjects over the PGI-I and CGI-I response categories were significant for”Tradamixina plus Seronea Repens” (PGI-I: p = 0.001; CGI-I). We also observed a decrease of total PSA. Conclusion The daily treatment with a new compound “Tradamixina plus

  6. Observational study: daily treatment with a new compound "Tradamixina" plus serenoa repens for two months improved the lower urinary tract symptoms.

    Science.gov (United States)

    Iacono, Fabrizio; Prezioso, Domenico; Illiano, Ester; Ruffo, Antonio; Romeo, Giuseppe; Amato, Bruno

    2012-01-01

    Lower urinary tract symptoms (LUTS) are associated with great emotional costs to individuals and substantial economic costs to society. This study seeks to evaluate the effect of a new natural compound "Tradamixina plus Serenoa Repens" in order to improve lower urinary tract symptoms. 100 patients (≥ 45 years) who had had LUTS/BPH for >6 mo at screening and with IPSS -The international Prostate symptom scores- ≥ 13 and maximum urinary flow rate (Qmax) ≥ 4 to ≤ 15 ml/s. were recruited. The compound "Tradamixina plus Serenoa Repens" (80 mg of Alga Ecklonia Bicyclis, 100 mg of Tribulus Terrestris and 100 mg of D-Glucosamine and N-Acetyl-D-Glucosamine plus 320 mg of Serenoa Repens) was administered daily for 2 months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical urological history, clinical examination, laboratory investigations (total PSA), and instrumental examination like urolfowmetry. Efficacy measures included IPSS-International Prostate Sympto, BPH Impact Index (BII), Quality-of-Life (QoL) Index. Measures were assessed at baseline and end point (12 wk or end of therapy) and also at screening, 1 and 4 wk for IPSS, and 4 wk for BII. Statistical significance was interpreted only if the results of the preceding analysis were significant at the 0.05 level. After 2 months of treatment the change from baseline to week 12 relative to "Tradamixina plus Seronea Repens" in total IPSS and Qol was statistically significant. Differences from baseline in BII were statistically significant for "Tradamixina plus Seronea Repens" above all differences in BII were also significant at 4 wk (LSmean ± SE: -0.8 ± 0.2). In the distribution of subjects over the PGI-I and CGI-I response categories were significant for"Tradamixina plus Seronea Repens" (PGI-I: p = 0.001; CGI-I). We also observed a decrease of total PSA. The daily treatment with a new compound "Tradamixina plus Serenoa Repens" for 2 months improved the male sexual

  7. Reversibility of endothelial dysfunction in diabetes: role of polyphenols.

    Science.gov (United States)

    Suganya, N; Bhakkiyalakshmi, E; Sarada, D V L; Ramkumar, K M

    2016-07-01

    The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

  8. Rapid flow-induced responses in endothelial cells

    Science.gov (United States)

    Stamatas, G. N.; McIntire, L. V.

    2001-01-01

    Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

  9. A strain of Saccharomyces cerevisiae evolved for fermentation of lignocellulosic biomass displays improved growth and fermentative ability in high solids concentrations and in the presence of inhibitory compounds

    Directory of Open Access Journals (Sweden)

    Hawkins Gary M

    2011-11-01

    Full Text Available Abstract Background Softwoods are the dominant source of lignocellulosic biomass in the northern hemisphere, and have been investigated worldwide as a renewable substrate for cellulosic ethanol production. One challenge to using softwoods, which is particularly acute with pine, is that the pretreatment process produces inhibitory compounds detrimental to the growth and metabolic activity of fermenting organisms. To overcome the challenge of bioconversion in the presence of inhibitory compounds, especially at high solids loading, a strain of Saccharomyces cerevisiae was subjected to evolutionary engineering and adaptation for fermentation of pretreated pine wood (Pinus taeda. Results An industrial strain of Saccharomyces, XR122N, was evolved using pretreated pine; the resulting daughter strain, AJP50, produced ethanol much more rapidly than its parent in fermentations of pretreated pine. Adaptation, by preculturing of the industrial yeast XR122N and the evolved strains in 7% dry weight per volume (w/v pretreated pine solids prior to inoculation into higher solids concentrations, improved fermentation performance of all strains compared with direct inoculation into high solids. Growth comparisons between XR122N and AJP50 in model hydrolysate media containing inhibitory compounds found in pretreated biomass showed that AJP50 exited lag phase faster under all conditions tested. This was due, in part, to the ability of AJP50 to rapidly convert furfural and hydroxymethylfurfural to their less toxic alcohol derivatives, and to recover from reactive oxygen species damage more quickly than XR122N. Under industrially relevant conditions of 17.5% w/v pretreated pine solids loading, additional evolutionary engineering was required to decrease the pronounced lag phase. Using a combination of adaptation by inoculation first into a solids loading of 7% w/v for 24 hours, followed by a 10% v/v inoculum (approximately equivalent to 1 g/L dry cell weight into 17

  10. Effects of Parietaria judaica pollen extract on human microvascular endothelial cells.

    Science.gov (United States)

    Taverna, Simona; Flugy, Anna; Colomba, Paolo; Barranca, Marilisa; De Leo, Giacomo; Alessandro, Riccardo

    2008-08-08

    Pollinosis from Parietaria judaica is one of the main causes of allergy in the Mediterranean area. The present study is designed to assess if P. judaica pollens contain bioactive compounds able to elicit a functional response in endothelial cells. We have demonstrated that addition of pollen extract to human lung microvascular endothelial cells (HMVEC-L) induces a modification of cell morphology, actin cytoskeletal rearrangements and an increase in endothelial cell permeability. We further showed that the treatment of endothelial cells with pollen extract causes an increase of E-selectin and VCAM-1 protein levels as well as an increase of IL-8 production. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of polymorphonuclear cells (PMNs) to HMVEC-L monolayer. Our results suggest for the first time that pollen affect directly endothelial cells (EC) modulating critical functions related to the inflammatory response.

  11. Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities.

    Science.gov (United States)

    Aman, Jurjan; Weijers, Ester M; van Nieuw Amerongen, Geerten P; Malik, Asrar B; van Hinsbergh, Victor W M

    2016-08-01

    Despite considerable progress in the understanding of endothelial barrier regulation and the identification of approaches that have the potential to improve endothelial barrier function, no drug- or stem cell-based therapy is presently available to reverse the widespread vascular leak that is observed in acute respiratory distress syndrome (ARDS) and sepsis. The translational gap suggests a need to develop experimental approaches and tools that better mimic the complex environment of the microcirculation in which the vascular leak develops. Recent studies have identified several elements of this microenvironment. Among these are composition and stiffness of the extracellular matrix, fluid shear stress, interaction of endothelial cells (ECs) with pericytes, oxygen tension, and the combination of toxic and mechanic injurious stimuli. Development of novel cell culture techniques that integrate these elements would allow in-depth analysis of EC biology that closely approaches the (patho)physiological conditions in situ. In parallel, techniques to isolate organ-specific ECs, to define EC heterogeneity in its full complexity, and to culture patient-derived ECs from inducible pluripotent stem cells or endothelial progenitor cells are likely to advance the understanding of ARDS and lead to development of therapeutics. This review 1) summarizes the advantages and pitfalls of EC cultures to study vascular leak in ARDS, 2) provides an overview of elements of the microvascular environment that can directly affect endothelial barrier function, and 3) discusses alternative methods to bridge the gap between basic research and clinical application with the intent of improving the translational value of present EC culture approaches. Copyright © 2016 the American Physiological Society.

  12. Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

    Directory of Open Access Journals (Sweden)

    Yumiko Mitome-Mishima

    Full Text Available After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.

  13. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  14. Physical inactivity causes endothelial dysfunction in healthy young mice.

    Science.gov (United States)

    Suvorava, Tatsiana; Lauer, Nadine; Kojda, Georg

    2004-09-15

    We sought to determine if physical inactivity affects endothelial function in young healthy individuals. Recent studies have linked exercise training to increased bioavailability of vascular nitric oxide (NO) and to improved endothelial function in patients with cardiovascular disorders. The effects of physical inactivity on normal vascular endothelial function are not known. Healthy young male C57Bl/6 mice living in groups of five in large cages, where they were running, climbing, and fighting during their active cycle, were randomly assigned to stay there or to live alone in small cages where they were predominantly resting. After five and nine weeks citrate synthase activity (a measure of mitochondrial respiratory chain activity), heart weight/body weight ratio, vascular reactivity, and protein expression of endothelial nitric oxide synthase (eNOS) were assessed. Singularized mice showed a reduction of citrate synthase activity (p effect on aortic eNOS expression. In young healthy individuals physical inactivity induces endothelial dysfunction, which is completely reversible by a short period of moderate exercise training. We suggest that physical inactivity, the so-called sedentary lifestyle, increases cardiovascular risk in young healthy individuals by inducing endothelial dysfunction.

  15. The influence of biomaterials on endothelial cell thrombogenicity

    Science.gov (United States)

    McGuigan, Alison P.; Sefton, Michael V.

    2007-01-01

    Driven by tissue engineering and regenerative medicine, endothelial cells are being used in combination with biomaterials in a number of applications for the purpose of improving blood compatibility and host integration. Endothelialized vascular grafts are beginning to be used clinically with some success in some centers, while endothelial seeding is being explored as a means of creating a vasculature within engineered tissues. The underlying assumption of this strategy is that when cultured on artificial biomaterials, a confluent layer of endothelial cells maintain their non-thrombogenic phenotype. In this review the existing knowledge base of endothelial cell thrombogenicity cultured on a number of different biomaterials is summarized. The importance of selecting appropriate endpoint measures that are most reflective of overall surface thrombogenicity is the focus of this review. Endothelial cells inhibit thrombosis through three interconnected regulatory systems (1) the coagulation cascade (2) the cellular components of the blood such as leukocytes and platelets and (3) the complement cascade, and also through effects on fibrinolysis and vascular tone, the latter which influences blood flow. Thus, in order to demonstrate the thromobgenic benefit of seeding a biomaterial with EC, the conditions under which EC surfaces are more likely to exhibit lower thrombogenicity than unseeded biomaterial surfaces need to be consistent with the experimental context. The endpoints selected should be appropriate for the dominant thrombotic process that occurs under the given experimental conditions. PMID:17316788

  16. Vascular endothelial growth factor overexpression in ischemic skeletal muscle enhances myoglobin expression in vivo

    NARCIS (Netherlands)

    van Weel, Vincent; Deckers, Martine M. L.; Grimbergen, Jos M.; van Leuven, Kees J. M.; Lardenoye, JanWillem H. P.; Schlingemann, Reinier O.; van Nieuw Amerongen, Geerten P.; van Bockel, J. Hajo; van Hinsbergh, Victor W. M.; Quax, Paul H. A.

    2004-01-01

    Therapeutic angiogenesis using vascular endothelial growth factor ( VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for

  17. Prediction and characterization of an Mg-Al intermetallic compound with potentially improved ductility via orbital-free and Kohn-Sham density functional theory

    Science.gov (United States)

    Zhuang, Houlong L.; Chen, Mohan; Carter, Emily A.

    2017-10-01

    Magnesium-aluminum (Mg-Al) intermetallic compounds that form as precipitates can significantly influence the mechanical properties of Mg-Al alloys. A computational evaluation of known and unknown Mg-Al intermetallic compounds could help design new Mg-Al alloy microstructures with optimal properties. Here, we employ the cluster-expansion method with energies efficiently calculated with orbital-free density functional theory (OFDFT) and predict a new, metastable intermetallic compound Mg3Al with a D019 hexagonal structure that is slightly more stable than an alternative L12 cubic structure. We apply Kohn-Sham DFT (KSDFT) to accurately evaluate various metastability criteria for D019 and L12 Mg3Al, including Born’s criterion and phonon dispersion. We show that both Mg3Al crystalline phases satisfy the metastability criteria and hence should be at least metastable. We further compare ductility metrics for D019 and L12 Mg3Al to that of hexagonal-close-packed Mg by computing Pugh’s ratio and generalized stacking fault energies. The ductility is predicted to follow the order: D019 Mg3Al > L12 Mg3Al > Mg, based on the highest Pugh’s ratio and the lowest unstable stacking and twinning fault energies of D019 Mg3Al compared to that of Mg. We also predict a very low antiphase boundary energy for Mg3Al and therefore expect D019 Mg3Al to be beneficial for improving the ductility of Mg-rich Mg-Al alloys. A computational design of Mg-Al alloy microstructures may become possible by combining the strengths of both OFDFT and KSDFT, i.e., the efficiency of the former and the accuracy of the latter, as demonstrated here.

  18. Endothelial progenitor cells in vascular health: focus on lifestyle.

    Science.gov (United States)

    Van Craenenbroeck, Emeline M; Conraads, Viviane M

    2010-05-01

    Endothelial dysfunction, which is considered the functional equivalent of a disrupted balance between endothelial injury and repair, precedes overt atherosclerosis by many years. Although this phenomenon is part of the normal aging process, prevention of early and progressive endothelial dysfunction has become an important therapeutic target. Evidence has accumulated to show that endothelial progenitor cells (EPC), contribute substantially to preservation of a structurally and functionally intact endothelium. There has been considerable progress in our understanding of the various cell types that were in the past all covered by the term "EPC." EPC home to sites of endothelial injury and ischemia, where they proliferate, differentiate and integrate into the endothelial layer or exert a paracrine function by producing vascular growth factors. Although more emphasis has been put on the pharmacological approach of endothelial dysfunction, the effect of a healthy lifestyle, via mobilization and functional improvement of EPC, is increasingly recognized. This review will focus on successful lifestyle interventions that aim to maintain vascular health through beneficial actions on cell populations with vasculogenic potential ("EPC"). The role of physical activity and dietary recommendations, which are considered essential elements of a healthy lifestyle, will be particularly emphasized. A thorough understanding of the physiology of endothelial benefits, derived from such interventions, may help to implement these measures on top of classical drug therapy, but also provides a solid basis for primary prevention. The effects of additional elements of a comprehensive lifestyle advice, such as smoking cessation, weight and stress reduction, also comprise a modulation of EPC function and circulating numbers and are therefore included in this review as well. Copyright 2009 Elsevier Inc. All rights reserved.

  19. Descemet membrane endothelial keratoplasty and refractive surgery.

    Science.gov (United States)

    Tong, C Maya; Baydoun, Lamis; Melles, Gerrit R J

    2017-07-01

    Descemet membrane endothelial keratoplasty (DMEK) has become a first-line treatment in corneal endothelial diseases because of its exceptional clinical outcomes and low complication rates. Because of its improved refractive predictability, DMEK is now also considered for managing cases with endothelial decompensation following previous refractive procedures, or in combination with those. This article reviews the clinical outcomes in these cases and discusses the possibility of refractive interventions following DMEK. DMEK has been successfully performed in eyes after laser in-situ keratomileusis, eyes after anterior chamber intraocular lens (IOL) implantation and aphakic eyes. Often, DMEK is combined with cataract surgery (triple-DMEK). Initial reports on reducing the refractive cylinder by toric IOL implantation are available. Although there are some reports on phacoemulsification and IOL implantation after phakic DMEK, reports on laser refractive procedures following DMEK are lacking. In contrast to earlier keratoplasty techniques, DMEK induces on average only mild refractive shifts owing to the 'natural' restoration of the cornea. As such, DMEK may be ideal in managing corneal decompensation in refractive patients. However, further studies are required to assess the safety and efficacy of DMEK after refractive treatment and of refractive procedures following DMEK.

  20. Doinseunggitang Ameliorates Endothelial Dysfunction in Diabetic Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jung Joo Yoon

    2013-01-01

    Full Text Available Atherosclerosis, a chronic and progressive disease characterized by vascular inflammation, is a leading cause of death in diabetes patients. Doinseunggitang (DYSGT, traditional prescription, has been used for promoting blood circulation to remove blood stasis. The aim of this study was to investigate the beneficial effects of DYSGT on endothelial dysfunction in diabetic atherosclerosis animal model. Apolipoprotein E knockout (ApoE KO mice fed on a Western diet were treated with DYSGT (200 mg/kg/day. DYSGT significantly lowered blood glucose level and glucose tolerance as well as systolic blood pressure. Metabolic parameter showed that DYSGT markedly decreased triglyceride and LDL-cholesterol levels. In the thoracic aorta, the impairment of vasorelaxation response to acetylcholine and atherosclerotic lesion was attenuated by DYSGT. Furthermore, DYSGT restored the reduction of endothelial nitric oxide synthase (eNOS expression, leading to the inhibition of intracellular adhesion molecule-1 (ICAM-1 and endothelin-1 (ET-1 expression. In conclusion, DYSGT improved the development of diabetic atherosclerosis via attenuation of the endothelial dysfunction, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation. Therefore, these results suggest that Korean traditional prescription Doinseunggitang may be useful in the treatment and prevention of diabetic vascular complications.

  1. Thrombospondin-1 signaling through CD47 inhibits cell cycle progression and induces senescence in endothelial cells.

    Science.gov (United States)

    Gao, Qi; Chen, Kexin; Gao, Lu; Zheng, Yang; Yang, Yong-Guang

    2016-09-08

    CD47 signaling in endothelial cells has been shown to suppress angiogenesis, but little is known about the link between CD47 and endothelial senescence. Herein, we demonstrate that the thrombospondin-1 (TSP1)-CD47 signaling pathway is a major mechanism for driving endothelial cell senescence. CD47 deficiency in endothelial cells significantly improved their angiogenic function and attenuated their replicative senescence. Lack of CD47 also suppresses activation of cell cycle inhibitors and upregulates the expression of cell cycle promoters, leading to increased cell cycle progression. Furthermore, TSP1 significantly accelerates replicative senescence and associated cell cycle arrest in a CD47-dependent manner. These findings demonstrate that TSP1-CD47 signaling is an important mechanism driving endothelial cell senescence. Thus, TSP1 and CD47 provide attractive molecular targets for treatment of aging-associated cardiovascular dysfunction and diseases involving endothelial dysregulation.

  2. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    Science.gov (United States)

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-08-01

    Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

  3. Systematic evaluation of supported liquid extraction in reducing matrix effect and improving extraction efficiency in LC-MS/MS based bioanalysis for 10 model pharmaceutical compounds.

    Science.gov (United States)

    Jiang, Hongliang; Cao, Huachuan; Zhang, Yang; Fast, Douglas M

    2012-04-01

    In past a few years, there has been a large increase in the application of supported liquid extraction (SLE) for LC-MS/MS based bioanalysis due to its distinct practical advantage in reduced time cost, ease of operation and the feasibility for automation. The main purpose of this study was to systematically evaluate supported liquid extraction in reducing matrix effect and improving extraction efficiency/recovery under various extraction conditions with 10 model pharmaceutical compounds in liquid chromatography coupled to electrospray tandem mass spectrometry (LC-ESI-MS/MS) analysis. Selected compounds have diverse physicochemical properties where logP ranges from 0.1 to 6.24 and pK(a) ranges from 4.0 to 11.1. The factors that may have the impact on the recovery of analytes and phospholipids (PL) were assessed. Over 75% recovery was achieved for every analyte under its respectively optimized extraction conditions where the selection of the polarity of extraction solvent and buffered pH can be critical for efficient recovery. Furthermore, the matrix effect was assessed by postextraction spike and postcolumn infusion method. The matrix effect was considerably reduced for all analytes under most extraction conditions evaluated for SLE, compared with protein precipitation (PPT) method. The correlation between matrix effect and residual phospholipids in sample extract was clearly shown. Although analyte-dependent matrix effect was observed prominently in sample extract prepared by PPT, it was minimized by SLE sample preparation process that effectively removes the majority of phospholipids. Sample extracted by ethyl acetate contained more phospholipids and demonstrated stronger matrix effect than by other organic solvents. Water-miscible organic content, such as methanol and acetonitrile in samples prior to loading has significant impact on PL recovery when eluting with methyl tert-butyl ether. However, isopropanol does not enhance the recovery of PL when adding to

  4. Endothelial-regenerating cells: an expanding universe.

    Science.gov (United States)

    Steinmetz, Martin; Nickenig, Georg; Werner, Nikos

    2010-03-01

    Atherosclerosis is the most common cause for cardiovascular diseases and is based on endothelial dysfunction. A growing body of evidence suggests the contribution of bone marrow-derived endothelial progenitor cells, monocytic cells, and mature endothelial cells to vessel formation and endothelial rejuvenation. To this day, various subsets of these endothelial-regenerating cells have been identified according to cellular origin, phenotype, and properties in vivo and in vitro. However, the definition and biology, especially of endothelial progenitor cells, is complex and under heavy debate. In this review, we focus on current definitions of endothelial progenitor cells, highlight the clinical relevance of endothelial-regenerating cells, and provide new insights into cell-cell interactions involved in endothelial cell rejuvenation.

  5. Evaluation of the use of performance reference compounds in an Oasis-HLB adsorbent based passive sampler for improving water concentration estimates of polar herbicides in freshwater.

    Science.gov (United States)

    Mazzella, Nicolas; Lissalde, Sophie; Moreira, Sylvia; Delmas, François; Mazellier, Patrick; Huckins, James N

    2010-03-01

    Passive samplers such as the Polar Organic Chemical Integrative Sampler (POCIS) are useful tools for monitoring trace levels of polar organic chemicals in aquatic environments. The use of performance reference compounds (PRC) spiked into the POCIS adsorbent for in situ calibration may improve the semiquantitative nature of water concentration estimates based on this type of sampler. In this work, deuterium labeled atrazine-desisopropyl (DIA-d5) was chosen as PRC because of its relatively high fugacity from Oasis HLB (the POCIS adsorbent used) and our earlier evidence of its isotropic exchange. In situ calibration of POCIS spiked with DIA-d5 was performed, and the resulting time-weighted average concentration estimates were compared with similar values from an automatic sampler equipped with Oasis HLB cartridges. Before PRC correction, water concentration estimates based on POCIS data sampling rates from a laboratory calibration exposure were systematically lower than the reference concentrations obtained with the automatic sampler. Use of the DIA-d5 PRC data to correct POCIS sampling rates narrowed differences between corresponding values derived from the two methods. Application of PRCs for in situ calibration seems promising for improving POCIS-derived concentration estimates of polar pesticides. However, careful attention must be paid to the minimization of matrix effects when the quantification is performed by HPLC-ESI-MS/MS.

  6. Endothelial dysfunction associated with obesity and the effect of weight loss interventions.

    Science.gov (United States)

    Kerr, S M P; Livingstone, M B E; McCrorie, T A; Wallace, J M W

    2011-11-01

    Endothelial damage is central to the initiation and progression of atherosclerosis, while in addition vascular endothelial cells secrete several anti-atherogenic substances including the potent vasodilator nitric oxide. Increased adhesion molecule expression, in response to pathophysiological stimuli is perhaps the earliest indicator of compromised endothelial integrity. Obesity and adiposity are associated with an increased risk of CVD, influencing disease progression via a number of mechanisms, including enhanced endothelial activation. This review discusses possible mechanisms linking adiposity and more specifically regional fat depots with endothelial function and evaluates studies investigating the effect of weight loss on endothelial function, assessed by biochemical and physiological measurements. Overall, the research to date suggests that visceral adiposity is a stronger predictor of endothelial activation than overall adiposity, possibly mediated via the action of NEFA in circulation. While in general there is a suggestion that weight loss is associated with significant improvements in endothelial function, this is not apparent in all interventions and published literature to date provides less than convincing evidence for the effects of weight loss on endothelial activation.

  7. Expansion and cryopreservation of porcine and human corneal endothelial cells.

    Science.gov (United States)

    Marquez-Curtis, Leah A; McGann, Locksley E; Elliott, Janet A W

    2017-08-01

    Impairment of the corneal endothelium causes blindness that afflicts millions worldwide and constitutes the most often cited indication for corneal transplants. The scarcity of donor corneas has prompted the alternative use of tissue-engineered grafts which requires the ex vivo expansion and cryopreservation of corneal endothelial cells. The aims of this study are to culture and identify the conditions that will yield viable and functional corneal endothelial cells after cryopreservation. Previously, using human umbilical vein endothelial cells (HUVECs), we employed a systematic approach to optimize the post-thaw recovery of cells with high membrane integrity and functionality. Here, we investigated whether improved protocols for HUVECs translate to the cryopreservation of corneal endothelial cells, despite the differences in function and embryonic origin of these cell types. First, we isolated endothelial cells from pig corneas and then applied an interrupted slow cooling protocol in the presence of dimethyl sulfoxide (Me 2 SO), with or without hydroxyethyl starch (HES). Next, we isolated and expanded endothelial cells from human corneas and applied the best protocol verified using porcine cells. We found that slow cooling at 1 °C/min in the presence of 5% Me 2 SO and 6% HES, followed by rapid thawing after liquid nitrogen storage, yields membrane-intact cells that could form monolayers expressing the tight junction marker ZO-1 and cytoskeleton F-actin, and could form tubes in reconstituted basement membrane matrix. Thus, we show that a cryopreservation protocol optimized for HUVECs can be applied successfully to corneal endothelial cells, and this could provide a means to address the need for off-the-shelf cryopreserved cells for corneal tissue engineering and regenerative medicine. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction.

    Science.gov (United States)

    Yu, Xuhua; Xu, Jiajun; Huang, Guoyang; Zhang, Kun; Qing, Long; Liu, Wenwu; Xu, Weigang

    2017-01-01

    Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects of bubble

  9. Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction.

    Directory of Open Access Journals (Sweden)

    Xuhua Yu

    Full Text Available Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects

  10. Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells

    Directory of Open Access Journals (Sweden)

    Maria Magdalena eMontt-Guevara

    2015-07-01

    Full Text Available Estetrol (E4 is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO is a key player for vascular function and disease during pregnancy and throughout ageing in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS in cultured human umbilical vein endothelial cells (HUVEC. E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2 and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use.

  11. Endothelial cells, fibroblasts and vasculitis.

    Science.gov (United States)

    Buckley, Christopher D; Rainger, G Ed; Nash, Gerard B; Raza, Karim

    2005-07-01

    One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-alpha and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-alpha and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.

  12. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.

    2014-03-01

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  13. Endothelial function in vasovagal syncope.

    Science.gov (United States)

    Pietrucha, Artur Z

    2014-12-01

    Vasovagal syncope (VVS) is a common form of fainting. The pathophysiology of VVS is complex and involves changes in the autonomic and vascular tone, resulting in reflex bradycardia with marked hypotension. Paradoxical peripheral vasodilation caused by endothelial dysfunction may also play a key role in inappropriate hypotension during VVS. Endothelial hyperactivity due to up regulation of nitric oxide synthase leads to profound vasodilation, much stronger than vasodilation caused by adrenergic stimulation in response to orthostatic stress alone. Studies have reported significantly higher flow-mediated dilation and higher plasma nitric oxide concentration in people with vasovagal syndrome. Patients with VVS showed decreased vasoconstrictive agent endothelin-1 levels during orthostatic stress. Coagulation and fibrinolysis activity also play important roles in endothelial function in syncopal patients. The response of the endothelium to orthostatic stress is similar to the reaction to haemorrhagic stress and is likely to be a remnant from the evolutionary adaptation of primates.

  14. Endothelial keratoplasty: evolution and horizons

    Directory of Open Access Journals (Sweden)

    Gustavo Teixeira Grottone

    2012-12-01

    Full Text Available Endothelial keratoplasty has been adopted by corneal surgeons worldwide as an alternative to penetrating keratoplasty (PK in the treatment of corneal endothelial disorders. Since the first surgeries in 1998, different surgical techniques have been used to replace the diseased endothelium. Compared with penetrating keratoplasty, all these techniques may provide faster and better visual rehabilitation with minimal change in refractive power of the transplanted cornea, minimal induced astigmatism, elimination of suture-induced complications and late wound dehiscence, and a reduced demand for postoperative care. Translational research involving cell-based therapy is the next step in work on endothelial keratoplasty. The present review updates information on comparisons among different techniques and predicts the direction of future treatment.

  15. Applications of anterior chamber paracentesis with improved compound trabeculectomy for persistent state of high IOP in patients with acute angle-closure glaucoma

    Directory of Open Access Journals (Sweden)

    Hai-Jia Xu

    2016-05-01

    Full Text Available AIM:To investigate the effect of anterior chamber paracentesis combined with improved compound trabeculectomy for persistent state of high intraocular press(IOPin patients with acute angle-closure glaucoma(AACGfailed in drug control. METHODS:Thirty-seven AACG patients(37 eyeswith persistent state of high IOP admitted in our hospital from June 2011 to June 2015 were selected. Vision:there was light perception in 2 eyes, hand movement in 3 eyes, finger count in 6 eyes, 0.01 in 8 eyes, 0.05 in 6 eyes, 0.1 in 5 eyes, 0.2 in 3 eyes, 0.25 in 2 eyes, 0.3 in 2 eyes; IOP:40-50 mmHg in 14 eyes, 51-60 mmHg in 11 eyes, 61-70 mmHg in 7 eyes, 71-80mmHg in 5 eyes; Anterior chamber:29 patients gotⅡ grade shallow anterior chamber and 8 patients got Ⅲ grade. After 24-72h of comprehensive ocular hypotensive medications failed to control IOP, paracentesis was applied. At 1-2d after IOP dropped to 21mmHg or less, patients received trabeculectomy combined with goniosynechialysis and mitomycin(MMC. Postoperative systemic and topical anti-inflammatory, anti-infection, symptomatic treatments were applied. RESULTS:Postoperative vision was 0.1-0.2 in 3 eyes, 0.25 in 4 eyes, 0.3 in 6 eyes, 0.4 in 8 eyes, 0.5 in 7 eyes, 0.6 in 6 eyes and 0.8 or more in 3 eyes. Postoperative IOP was controlled within 10-21mmHg without medication in 26 eyes, within 23-27mmHg with 1-2 kinds of anti-glaucoma medications in 8 eyes, 3 eyes failed in drug decompression with 2-3 medications and remained high IOP of 30-38mmHg at last underwent surgery again. The chamber grading was grade Ⅰ in 28 eyes, grade Ⅱ in 6 eyes, Ⅲ grade in 3 eyes. Filtering bleb type was type Ⅰ of functional filtering bleb in 21 eyes, type Ⅱ functional filtering bleb in 13 eyes, type Ⅲ of non-functional filtering bleb in 2 eyes, type Ⅳ of non-functional filtering bleb in 1 eyes. No case occurred complications such as fulminant choroidal hemorrhage, vitreous loss or postoperative malignant glaucoma. There

  16. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

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

  17. HA/TCP compounding of a porous CaP biomaterial improves bone formation and scaffold degradation--a long-term histological study.

    Science.gov (United States)

    Schopper, Christian; Ziya-Ghazvini, Farzad; Goriwoda, Walter; Moser, Doris; Wanschitz, Felix; Spassova, Else; Lagogiannis, Georgios; Auterith, Alexandra; Ewers, Rolf

    2005-07-01

    In the present study, two biphasic calcium phosphate biomaterials (BCP) with HA/TCP ratios of 50/50 and 30/70 were obtained from a pure HA biomaterial. The biomaterials which showed the same three-dimensional geometry were implanted into corticocancellous costal defects of sheep. In the specimens of all three biomaterials, abundant bone formation, mineral dissolution from the biomaterial scaffolds, and active cellular resorption of the scaffolds was present after 6 and 12 months. Backscattered electron microscopy showed bone invasion into the pores of the scaffolds and micromechanical interlocking at the bone/biomaterial interface without intervening soft tissue. The pattern of bone formation and scaffold resorption was different for cortical and cancellous bone. No time-based effect, however, was observed. Overall, the BCP biomaterials had formed significantly more bone than the HA biomaterial. Also, scaffold resorption, which was followed by a replacement with newly formed bone, was significantly higher in the BCP biomaterials. Although no significant differences were observed between both BCP biomaterials, the present study had confirmed the assumption that HA/TCP compounding was suitable to improve bone formation and scaffold resorption in the investigated biomaterials and at the same time maintain the osteoconductive properties of the scaffolds. Copyright 2005 Wiley Periodicals, Inc.

  18. Magnetizable stent-grafts enable endothelial cell capture

    Science.gov (United States)

    Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

    2017-04-01

    Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

  19. Precut tissue for Descemet's stripping automated endothelial keratoplasty: vision, astigmatism, and endothelial survival.

    Science.gov (United States)

    Terry, Mark A; Shamie, Neda; Chen, Edwin S; Phillips, Paul M; Hoar, Karen L; Friend, Daniel J

    2009-02-01

    To report 6 and 12 month results using precut tissue for Descemet's stripping automated endothelial keratoplasty (DSAEK) and correlate donor characteristics with clinical outcomes. Prospective, noncomparative, interventional case series. We reviewed 100 donor corneas precut for 100 eyes of 90 DSAEK patients. Our first 100 consecutive cases of DSAEK with precut tissue were entered into a prospective protocol. Donor characteristics and the visual, refractive, topographic, and specular microscopy results at 6 and 12 months were analyzed. Correlation analysis comparing donor characteristics with clinical outcomes was performed. Six- and 12-month postoperative best spectacle-corrected visual acuity (BSCVA), refractive astigmatism, topographic keratometry (K), and specular endothelial cell densities (ECD) were measured prospectively and then compared with preoperative values. Donor characteristics analyzed included death to preservation time, death to surgery time, precutting resection to surgery time, and graft thickness. Six months after DSAEK surgery, BSCVA improved from 20/83 to 20/38. (P/=20/40 at 6 months and 20% obtained > or =20/20. Astigmatism changed an average of 0.09 diopters (D) and K changed by +0.09 D, both of which were not significant and were stable to 12 months. The postoperative mean ECD (n = 65) was 1918 cells/mm(2) at 6 months, and represented a 31% cell loss from preoperatively (Pastigmatism. Donor endothelial cell loss from 6 to 12 months is stable and is comparable with reports involving tissue that is cut intraoperatively. Proprietary or commercial disclosures may be found after the references.

  20. Evaluation of endothelial function in exogenous subclinical hyperthyroidism and the effect of treatment

    Directory of Open Access Journals (Sweden)

    Sayed Mohammad Hosseini

    2016-01-01

    Conclusions: This study demonstrated that FMD decreased in exogenous subclinical hyperthyroid patients which could be partially restored by treatment. These findings suggest that treatment of subclinical hyperthyroid state could improve endothelial dysfunction and at the end decreased the cardiovascular complications.

  1. Topographic characteristics after Descemet's membrane endothelial keratoplasty and Descemet's stripping automated endothelial keratoplasty.

    Directory of Open Access Journals (Sweden)

    Takahiko Hayashi

    Full Text Available To investigate the topographic characteristics of the posterior corneal surface after Descemet's endothelial membrane keratoplasty (DMEK and Descemet's stripping automated endothelial keratoplasty (DSAEK and their effects on postoperative visual acuity.Nineteen eyes of 19 patients after DMEK, 23 eyes of 23 patients after DSAEK, and 18 eyes of 18 control subjects were retrospectively analyzed. Best spectacle-corrected visual acuity (BSCVA, aberration factors (higher-order aberrations [HOAs], spherical aberrations [SAs], and coma aberrations [Comas] at 6.0 mm were evaluated preoperatively and at 1, 3, and 6 months postoperatively. The posterior refractive pattern of the topography map was classified into 5 grades (0-5 (posterior color grade using anterior segment optical coherence tomography. Correlations between BSCVA and some factors (abbreviation factors, posterior color grade were analyzed.BSCVA was significantly better after DMEK than after DSAEK (P < 0.001. Posterior HOAs, SAs, and Comas after each type of endothelial keratoplasty were significantly greater compared to control (P < 0.01. Posterior HOAs, total/anterior/posterior SAs, and posterior color grade were significantly lower in the DMEK group than in the DSAEK group at 3 months (P < 0.024 [posterior HOAs], P = 0.047 [total SA], P < 0.001 [anterior SAs], P = 0.021 [posterior SAs], and P < 0.001 [posterior color grade] and 6 months postoperatively (P = 0.034 [posterior HOAs], P < 0.001 [total SAs], P < 0.001 [anterior SAs], P = 0.013 [posterior SAs], and P = 0.004 [posterior color grade]. BSCVA was significantly correlated with HOAs, SAs, and posterior color grade (P < 0.001 for all except anterior HOAs [P = 0.004].High posterior color grades were associated with larger aberration factors and had a negative effect on visual function after endothelial keratoplasty. Rapid improvement of visual function after DMEK may be attributed to less change at the posterior surface.

  2. Smoking Counteracts the Favorable Effect of Exercise Training on Endothelial Function in Patients with Type 2 Diabetes

    OpenAIRE

    Sato, Shinji; Nakayama, Noriko; Otsuki, Shingo; Tanaka, Shiro; Nakamura, Hajime; Koshiyama, Hiroyuki; Nohara, Ryuji

    2013-01-01

    Background Exercise training can improve endothelial function in patients with diabetes. We hypothesized that the favorable effect of exercise training on endothelial function in patients with diabetes is counteracted by cigarette smoking. Purpose: To assess whether there is a difference in the effect of exercise on endothelial function in smokers and non-smokers with type 2 diabetes. Methods: We performed a 3-month controlled trial in 27 never-smoking and 17 smoking individuals with type 2 d...

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

    Science.gov (United States)

    Choi, Eun-Yong; Lee, Hansongyi; Woo, Jong Shin; Jang, Hyun Hee; Hwang, Seung Joon; Kim, Hyun Soo; Kim, Woo-Sik; Kim, Young-Seol; Choue, Ryowon; Cha, Yong-Jun; Yim, Jung-Eun; Kim, Weon

    2015-09-01

    Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. Medium-term administration of OPE an improvement in FMD and circulating EPCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Comparative angioprotective effects of magnesium compounds.

    Science.gov (United States)

    Kharitonova, Maria; Iezhitsa, Igor; Zheltova, Anastasia; Ozerov, Alexander; Spasov, Alexander; Skalny, Anatoly

    2015-01-01

    Magnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which was accompanied by a reduced concentration of eNOs and increased levels of endothelin-1 level in the serum and impaired endothelium-dependent vasodilatation. These effects increased the concentration of proinflammatory molecules, such as VCAM-1, TNF-α, IL-6 and CRP, indicating the development of systemic inflammation and endothelial dysfunction. The increased total NO level, which estimated from the sum of the nitrate and nitrite concentrations in the serum, may also be considered to be a proinflammatory marker. Two weeks of Mg supplementation partially or fully normalised the ability of the vascular wall to effect adequate endothelium-dependent vasodilatation and reversed the levels of most endothelial dysfunction and inflammatory markers (except CRP) to the mean values of the control group. Mg sulphate had the smallest effect on the endothelin-1, TNF-α and VCAM-1 levels. Mg N-acetyltaurate was significantly more effective in restoring the level of eNOS compared to all other studied compounds, except for Mg oxybutyrate. Taken together, the present findings demonstrate that all Mg compounds equally alleviate endothelial dysfunction and inflammation caused by Mg deficiency. Mg sulphate tended to be the least effective compound. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jingshan Zhao

    Full Text Available The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL, a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF signaling and angiogenesis in endothelial cells (ECs. We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.

  6. Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.

    Science.gov (United States)

    Zhao, Jingshan; Niu, Honglin; Li, Aiying; Nie, Lei

    2016-01-01

    The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL), a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF) signaling and angiogenesis in endothelial cells (ECs). We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day) recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.

  7. Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy.

    Science.gov (United States)

    Nanavaty, Mayank A; Wang, Xue; Shortt, Alex J

    2014-02-14

    Fuchs endothelial dystrophy (FED) is a condition in which there is premature degeneration of corneal endothelial cells. When the number of endothelial cells is reduced to a significant degree, fluid begins to accumulate within the cornea. As a result, the cornea loses its transparency and the individual suffers a reduction in vision. The only successful surgical treatment for this condition is replacement of part or all of the cornea with healthy tissue from a donor. The established procedure, penetrating keratoplasty (PKP), has been used for many years and its safety and efficacy are well known. Endothelial keratoplasty (EK) techniques are relatively new surgical procedures and their safety and efficacy relative to PKP are uncertain. The objective of this review was to compare the benefits and complications related to two surgical methods (EK and PKP) of replacing the diseased endothelial layer of the cornea with a healthy layer in people with FED. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1950 to January 2014), EMBASE (January 1980 to January 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 27 January 2014. We included all randomised controlled trials (RCTs) comparing EK versus PKP for people (of any age and gender) who had been clinically diagnosed with FED. Two authors independently screened the search results, assessed trial quality and extracted data using the standard methodological procedures expected by The Cochrane Collaboration. We included three RCTs that enrolled a total of 139 eyes of 136 participants and analysed 123 (88%) eyes. Two RCTs

  8. Evaluation of a static stretching intervention on vascular endothelial function and arterial stiffness.

    Science.gov (United States)

    Shinno, Hiromi; Kurose, Satoshi; Yamanaka, Yutaka; Higurashi, Kyoko; Fukushima, Yaeko; Tsutsumi, Hiromi; Kimura, Yutaka

    2017-06-01

    Maintenance and enhancement of vascular endothelial function contribute to the prevention of cardiovascular disease and prolong a healthy life expectancy. Given the reversible nature of vascular endothelial function, interventions to improve this function might prevent arteriosclerosis. Accordingly, we studied the effects of a 6-month static stretching intervention on vascular endothelial function (reactive hyperaemia peripheral arterial tonometry index: RH-PAT index) and arterial stiffness (brachial-ankle pulse wave velocity: baPWV) and investigated the reversibility of these effects after a 6-month detraining period following intervention completion. The study evaluated 22 healthy, non-smoking, premenopausal women aged ≥40 years. Subjects were randomly assigned to the full-intervention (n = 11; mean age: 48.6 ± 2.8 years) or a half-intervention that included a control period (n = 11; mean age: 46.9 ± 3.6 years). Body flexibility and vascular endothelial function improved significantly after 3 months of static stretching. In addition to these improvements, arterial stiffness improved significantly after a 6-month intervention. However, after a 6-month detraining period, vascular endothelial function, flexibility, and arterial stiffness all returned to preintervention conditions, demonstrating the reversibility of the obtained effects. A 3-month static stretching intervention was found to improve vascular endothelial function, and an additional 3-month intervention also improved arterial stiffness. However, these effects were reversed by detraining.

  9. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

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

  10. The involvement of endothelial mediators in leprosy.

    Science.gov (United States)

    Nogueira, Maria Renata Sales; Latini, Ana Carla Pereira; Nogueira, Maria Esther Salles

    2016-10-01

    Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

  11. Acute oral tetrahydrobiopterin administration ameliorates endothelial dysfunction in systemic sclerosis.

    Science.gov (United States)

    Machin, Daniel R; Clifton, Heather L; Richardson, Russell S; Wray, D Walter; Donato, Anthony J; Frech, Tracy M

    2017-01-01

    Systemic sclerosis (SSc) is a rare, autoimmune disease characterised by endothelial dysfunction, which is associated with peripheral vasculopathy, such as digital ulcers (DU). We sought to determine if acute oral administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase, would augment endothelial function in patients with SSc. Twelve SSc patients, of whom a majority had a history of DU, were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design. There were no differences in blood markers of oxidative stress and brachial artery blood pressure, diameter, blood velocity, shear rate, or blood flow at rest between placebo and BH4 (p>0.05). Whereas, after a 5 minute suprasystolic forearm cuff occlusion, brachial artery peak reactive hyperemia (placebo: 313±30 vs. BH4: 347±37 ml/min, pacute BH4 administration, indicating an improvement in endothelial function. To determine if the vasodilatory effects of BH4 were specific to the vascular endothelium, brachial artery blood flow and vasodilation in response to sublingual nitroglycerin were assessed, and were found to be unaffected by BH4 (p>0.05). These findings indicate that acute BH4 administration ameliorates endothelial dysfunction in patients with SSc. Given that endothelial dysfunction is known to be associated with DU in SSc patients, this study provides a proof-of-concept for the potential therapeutic benefits of BH4 in the prevention or treatment of DU in this population.

  12. Organic neem compounds inhibit soft‐rot fungal growth and improve the strength of anthracite bricks bound with collagen and lignin for use in iron foundry cupolas

    National Research Council Canada - National Science Library

    Kelsey, D.J; Nieto‐Delgado, C; Cannon, F.S; Brennan, R.A

    2015-01-01

    To examine organic neem compounds for their effective growth inhibition of saprotrophic soft-rot fungi on anthracite bricks bound with collagen and lignin for use in iron foundry cupolas as an alternative fuel source...

  13. Endothelial dysfunction: a comprehensive appraisal

    Directory of Open Access Journals (Sweden)

    Vilariño Jorge O

    2006-02-01

    Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

  14. Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients.

    Science.gov (United States)

    Horn, Patrick; Amabile, Nicolas; Angeli, Franca S; Sansone, Roberto; Stegemann, Berthold; Kelm, Malte; Springer, Matthew L; Yeghiazarians, Yerem; Schroeter, Hagen; Heiss, Christian

    2014-04-14

    Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144⁺ and CD31⁺/41⁻ EMP were inversely correlated with FMD (r -0.67, P=0.01 and r -0.59, P=0.01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31⁺/41⁻ and CD144⁺ EMP decreased (-25 and -23%, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity.

  15. Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition

    Directory of Open Access Journals (Sweden)

    Takio Inatomi

    2017-12-01

    Full Text Available Lactogenic immunity transferred to piglets after inoculation of a live vaccine to pregnant sows was proved limited to control porcine epidemic diarrhea (PED. Hence, here we evaluated the efficacy of administration of a probiotic compound containing Bacillus mesentericus, Clostridium butyricum, and Enterococcus faecalis together with a commercial live-attenuated PED vaccine (Nisseiken PED Live Vaccine, Nisseiken, Tokyo, Japan to improve the health and reproductive performance of PED-infected sows. Twenty pregnant sows in a PED-positive farm were equally divided into probiotics-administered (VP and control (VC sow groups. A commercial live-attenuated vaccine was injected as per the manufacturer’s instruction. The probiotic compound (15 g/day was orally administered to VP from 6 weeks pre-parturition to 7 days post-parturition (ppd7. VP had a significantly higher body weight at ppd7 than VC (191 vs 186 kg; P < 0.05. At day 3 post-parturition (ppd3 (4.18 vs 3.63 kg/day and ppd7 (5.14 vs 4.34 kg/day, milk produced by VP was significantly (P < 0.05 greater than that by VC. Total immunoglobulin (IgA and IgG concentrations at day 0 were significantly (P < 0.05 higher in whey of VP (1.9 and 6.6 g/dL, respectively than in that of VC (1.7 and 6.1 g/dL, respectively. However, total IgG concentration in whey of VP and VC at ppd3 and ppd7 did not differ. Antibody titer was significantly higher at day 0 in serum of VP than it was that of VC (60 vs 37 in geometric mean; P < 0.05. Likewise, the antibody titer in whey of VP and VC was found to be similar at day 0 (416 vs 208 in geometric mean; P = 0.13. Consequently, VP had fewer days between weaning and return to estrus than did VC (7 vs 10 days; P < 0.05. Moreover, piglets of VP had a significantly (P < 0.05 higher litter weight at birth (9,252 g/litter and a lower mortality (12% during suckling than those of VC (8,686 g/litter and 28%, respectively. In

  16. Human Induced Pluripotent Stem Cell-Derived Endothelial Cells for Three-Dimensional Microphysiological Systems.

    Science.gov (United States)

    Kurokawa, Yosuke K; Yin, Rose T; Shang, Michael R; Shirure, Venktesh S; Moya, Monica L; George, Steven C

    2017-08-01

    Microphysiological systems (MPS), or "organ-on-a-chip" platforms, aim to recapitulate in vivo physiology using small-scale in vitro tissue models of human physiology. While significant efforts have been made to create vascularized tissues, most reports utilize primary endothelial cells that hinder reproducibility. In this study, we report the use of human induced pluripotent stem cell-derived endothelial cells (iPS-ECs) in developing three-dimensional (3D) microvascular networks. We established a CDH5-mCherry reporter iPS cell line, which expresses the vascular endothelial (VE)-cadherin fused to mCherry. The iPS-ECs demonstrate physiological functions characteristic of primary endothelial cells in a series of in vitro assays, including permeability, response to shear stress, and the expression of endothelial markers (CD31, von Willibrand factor, and endothelial nitric oxide synthase). The iPS-ECs form stable, perfusable microvessels over the course of 14 days when cultured within 3D microfluidic devices. We also demonstrate that inhibition of TGF-β signaling improves vascular network formation by the iPS-ECs. We conclude that iPS-ECs can be a source of endothelial cells in MPS providing opportunities for human disease modeling and improving the reproducibility of 3D vascular networks.

  17. Multipurpose Compound

    Science.gov (United States)

    1983-01-01

    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  18. Challenges in pediatric endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Vikas Mittal

    2014-01-01

    Full Text Available We performed endothelial keratoplasty (EK in three eyes of two siblings (2.5 years, male and 3.5 years, female with congenital hereditary endothelial dystrophy (CHED and report the intraoperative and postoperative difficulties. Repeated iris prolapse, apprehension of crystalline lens touch due to positive vitreous pressure, and need for frequent air injections to attach the graft were intraoperative challenges in all three eyes. These were addressed by use of Sheet′s glide instead of Busin′s glide during graft insertion and suturing of main and side ports before air injection. One eye had graft dislocation on second postoperative day due to eye rubbing by the child. Graft was repositioned with air and a venting incision was created. Postoperative examination required repeated general anesthesia. Corneal edema resolved completely in all three eyes. Present case series highlights the possible intraoperative and postoperative challenges and their solutions in pediatric EK for CHED.

  19. Flow-Mediated Endothelial Mechanotransduction

    Science.gov (United States)

    Davies, Peter F.

    2011-01-01

    Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed. PMID:7624393

  20. Infectious endotheliitis: a rare case of presumed mycotic origin

    Directory of Open Access Journals (Sweden)

    Zapata LF

    2013-07-01

    Full Text Available Luis Fernando Zapata,1 José David Paulo,1 Carlos A Restrepo,1 Luis Fernando Velásquez,2 Andrés E Toro Montoya,2 Melissa A Zapata21Department of Ophthalmology Hospital Pablo Tobón Uribe; 2School of Medicine, Universidad Pontificia Bolivariana, Medellín, ColombiaPurpose: To report an interesting case of infectious endotheliitis of presumed mycotic origin.Methods: A case report of a 56-year-old male farmer who sought medical attention after a month-long evolution of irritative symptoms in his right eye, accompanied by visual acuity (VA impairment. The patient received topical and oral broad-spectrum antibiotic treatment with no improvement before being referred to a cornea specialist, where he was found to have VA of 20/150 and was noted on biomicroscopy to have endothelial feathery coalescent lesions. The patient was admitted to the hospital for an aqueous humor sample and intravenous voriconazole.Results: The microbiological studies did not isolate any micro-organisms. However, clinical evidence of improvement was confirmed after 5 days of antimycotic intravenous therapy. Complete clinical resolution was achieved at 1 month after treatment completion with oral voriconazole, as evidenced by VA of 20/20 and disappearance of endothelial lesions.Conclusion: Endothelial involvement by fungi is a rare condition. In this case, no microbes were isolated, but the characteristic morphology of the lesions, the history of onychomycosis, and the spectacular response to voriconazole turn this case into a valid presumptive diagnosis.Keywords: endotheliitis, mycotic, keratitis, voriconazole

  1. Mesoionic Compounds

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 10. Mesoionic Compounds - An Unconventional Class of Aromatic Heterocycles. Bharati V Badami. General Article Volume 11 Issue 10 October 2006 pp 40-48. Fulltext. Click here to view fulltext PDF. Permanent link:

  2. Mesoionic Compounds

    Indian Academy of Sciences (India)

    Sydnone, the representative mesoionic compound has been extensively studied because of its unusual structure, chemi- cal properties and synthetic utility. Sydnone is used as a versatile synthon in heterocyclic synthesis. This article gives a brief account of the comparative studies of the structural features of mesoionic ...

  3. Allicin inhibits lymphangiogenesis through suppressing activation of vascular endothelial growth factor (VEGF) receptor.

    Science.gov (United States)

    Wang, Weicang; Du, Zheyuan; Nimiya, Yoshiki; Sukamtoh, Elvira; Kim, Daeyoung; Zhang, Guodong

    2016-03-01

    Allicin, the most abundant organosulfur compound in freshly crushed garlic tissues, has been shown to have various health-promoting effects, including anticancer actions. A better understanding of the effects and mechanisms of allicin on tumorigenesis could facilitate development of allicin or garlic products for cancer prevention. Here we found that allicin inhibited lymphangiogenesis, which is a critical cellular process implicated in tumor metastasis. In primary human lymphatic endothelial cells, allicin at 10 μM inhibited capillary-like tube formation and cell migration, and it suppressed phosphorylation of vascular endothelial growth factor receptor 2 and focal adhesion kinase. Using a Matrigel plug assay in mice, addition of 10 μg allicin in Matrigel plug inhibited 40-50% of vascular endothelial growth factor-C-induced infiltration of lymphatic endothelial cells and leukocytes. S-Allylmercaptoglutathione, a major cellular metabolite of allicin, had no effect on lymphangiogenic responses in lymphatic endothelial cells. Together, these results demonstrate the antilymphangiogenic effect of allicin in vitro and in vivo, suggesting a novel mechanism for the health-promoting effects of garlic compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction.

    Science.gov (United States)

    Bharat, Divya; Cavalcanti, Rafaela Ramos Mororo; Petersen, Chrissa; Begaye, Nathan; Cutler, Brett Ronald; Costa, Marcella Melo Assis; Ramos, Renata Kelly Luna Gomes; Ferreira, Marina Ramos; Li, Youyou; Bharath, Leena P; Toolson, Emma; Sebahar, Paul; Looper, Ryan E; Jalili, Thunder; Rajasekaran, Namakkal S; Jia, Zhenquan; Symons, J David; Pon Velayutham, Anandh Babu

    2017-10-12

    Lipotoxicity-induced endothelial dysfunction is an important vascular complication associated with diabetes. Clinical studies support the vascular benefits of blueberry anthocyanins, but the underlying mechanism is unclear. We tested the hypothesis that metabolites of blueberry anthocyanins attenuate lipotoxicity-induced endothelial dysfunction. Human aortic endothelial cells (HAECs) were treated for 6 h with either: (i) the parent anthocyanins (malvidin-3-glucoside and cyanidin-3-glucoside); or (ii) the blueberry metabolites (hydroxyhippuric acid, hippuric acid, benzoic acid-4-sulfate, isovanillic acid-3-sulfate, and vanillic acid-4-sulfate), at concentrations known to circulate in humans following blueberry consumption. For the last 5 h HAECs were treated with palmitate or vehicle. HAECs treated with palmitate displayed elevated reactive oxygen species generation, increased mRNA expression of Nox4, chemokines, adhesion molecules, and IκBα, exaggerated monocyte binding, and suppressed nitric oxide production. Of note, the damaging effects of palmitate were ameliorated in HAECs treated with blueberry metabolites but not parent anthocyanins. Further, important translational relevance of these results was provided by our observation that palmitate-induced endothelial dysfunction was lessened in arterial segments that incubated concurrently with blueberry metabolites. Our findings indicate that the vascular benefits of blueberry anthocyanins are mediated by their metabolites. Blueberries might complement existing therapies to improve vascular complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Endothelial safety of radiological contrast media: why being concerned.

    Science.gov (United States)

    Scoditti, Egeria; Massaro, Marika; Montinari, Maria Rosa

    2013-01-01

    Iodinated radiocontrast media have been the most widely used pharmaceuticals for intravascular administration in diagnostic and interventional angiographic procedures. Although they are regarded as relatively safe drugs and vascular biocompatibility of contrast media has been progressively improved, severe adverse reactions may occur, among which acute nephropathy is one of the most clinically significant complications after intravascular administration of contrast media and a powerful predictor of poor early and long-term outcomes. Since radiocontrast media are given through the arterial or the venous circulation in vascular procedures, morphological and functional changes of the microvascular and macrovascular endothelial cells substantially contribute to the pathogenesis of organ-specific and systemic adverse reactions of contrast media. Endothelial toxicity of contrast media seems to be the result of both direct proapoptotic effects and morphological derangements, as well as endothelial dysfunction and induction of inflammation, oxidative stress, thrombosis, and altered vasomotor balance, with predominant vasoconstrictive response in atherosclerotic coronary arteries and kidney microcirculation. Further understanding of pathogenetic mechanisms underlying contrast media-induced adverse reactions in cellular targets, including endothelial cells, will hopefully lead to the development of novel preventive strategies appropriately curbing the pathogenesis of contrast media vasotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Coniferyl Aldehyde Ameliorates Radiation Intestine Injury via Endothelial Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ye Ji; Jung, Myung Gu; Lee, Yoonjin; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yunsil [Ewha Woman' s Univ., Seoul (Korea, Republic of); Ko, Younggyu [Korea Univ., Seoul (Korea, Republic of)

    2014-05-15

    Cancer treatments related gastrointestinal toxicity has also been recognized as a significant economic burden. Especially, extensive apoptosis of microvascular endothelial cell of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Coniferyl aldehyde (CA) is phenolic compounds isolated from cork stoppers, and one of the major pyrolysis products of lignin. Shi H. was support for the empirical use of CA as a medicinal food for cardiovascular diseases. CA has positive effect in broad way but there is no consequence in radiation induced intestine damage. Here, we investigate effect of CA on small intestine after abdominal IR to mice in this study. In this study, CA increased the survival rate in C3H mice against 13.5 Gy abdominal IR. We found CA protects small intestine via preventing endothelial cell apoptosis and enhancing their angiogenic activity. CA also showed protective effect on crypt cell survival. Endothelial cell survival may affect crypt cell protection against IR. From this data, we concluded that CA is effective for protection against abdominal radiation injury. CA could ameliorate side-effect of radiation therapy.

  7. Cataract surgery after Descemet stripping endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Sunita Chaurasia

    2012-01-01

    Full Text Available Management of endothelial dysfunction in phakic patients is sometimes a dilemma for corneal surgeons. Phakic patients with visually significant cataract and endothelial dysfunction are preferably managed by performing combined cataract surgery with endothelial keratoplasty. However, combined surgery may be deferred in eyes with early incipient cataract, younger age and where anterior chamber is poorly visualized. As cataract formation may be accelerated after endothelial keratoplasty, these eyes may need cataract surgery subsequently. Surgical intervention in eyes with endothelial keratoplasty is of concern as this may affect the graft adversely and threaten graft survival. In this report, we describe the intraoperative surgical details and postoperative clinical course of a patient who underwent phacoemulsification with intraocular lens implantation after Descemet stripping automated endothelial keratoplasty (DSAEK.

  8. Endothelial cell loss after autologous rotational keratoplasty.

    Science.gov (United States)

    Birnbaum, Florian; Reinhard, Thomas; Böhringer, Daniel; Sundmacher, Rainer

    2005-01-01

    To investigate whether it may be possible to ascertain the influence of immunological factors on chronic endothelial cell loss by comparing chronic endothelial cell loss after autologous rotational penetrating keratoplasty and after homologous penetrating keratoplasty. For six patients who had undergone autologous rotational penetrating keratoplasty the relative annual loss of endothelial cells was calculated by means of an exponential regression analysis. The findings were compared with those in a homogeneous historical control group (53 patients undergoing homologous penetrating keratoplasty for keratoconus). After autologous rotational keratoplasty relative annual loss of endothelial cells was 1.1%+/-2.6% (mean +/- standard deviation). Relative annual loss of endothelial cells in the control-group was 16.7%+/-20.8%. The results of the study lead to the assumption that immunological influences might be the main cause for chronic endothelial cell loss after homologous penetrating keratoplasty.

  9. Herpes Simplex Virus endotheliitis following descemet‘s membrane endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Siamak Zarei-Ghanavati1

    2015-01-01

    Conclusion:HSV endotheliitis may occur in the early postoperative period after DMEK and manifest as endothelial dysfunction leading to donor detachment. Anti-viral medication may help treat the acute phase and reduce the risk of recurrence.

  10. Preventive Effects of a Three-month Yoga Intervention on Endothelial Function in Patients with Migraine

    OpenAIRE

    Hajar Naji-Esfahani; Mahsa Zamani; Seyed Mohamad Marandi; Vahid Shaygannejad; Shaghayegh Haghjooy Javanmard

    2014-01-01

    Background: Migraine is a neurovascular disorder and any interventions improving endothelial function may contribute to its treatment and prevention of vascular complications like ischemic stroke. Yoga has been shown to have several beneficial effects on cardiovascular systems. However, no randomized controlled studies to date have investigated its effects on endothelial function of migraineurs. Methods: A total of 42 women patients with migraine were enrolled and randomized into either a...

  11. Endothelial Dysfunction and Its Correction in Patients with Essential Hypertension and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    A.S. Shalimova

    2014-03-01

    Full Text Available The article provides the results of studying the effectiveness of α-lipoic acid impact as a part of complex therapy on endothelial dysfunction in patients with essential hypertension and type 2 diabetes mellitus. There were revealed a significant improvement in metabolic homeostasis, decreased severity of endothelial dysfunction, reduced levels of inflammatory cytokines under additional use of α-lipoic acid compared with standard therapy.

  12. Effect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysis.

    Science.gov (United States)

    Pearson, M J; Smart, N A

    2017-03-15

    Endothelial dysfunction contributes to the development and progression of cardiovascular disease and heart failure (HF) and is associated with an increased risk of mortality. Flow-mediated dilation (FMD) is widely utilised to assess endothelial function and is improved with exercise training in heart failure patients. The aim of this meta-analysis is to quantify the effect of exercise training in patients with heart failure. A large number of studies now exist that have examined endothelial function in patients with heart failure. We sought to add to the current literature by quantifying the effect of exercise training on endothelial function. We conducted database searches (PubMed, EMBASE, PROQUEST and Cochrane Trials Register to June 2016) for exercise based rehabilitation trials in heart failure, using search terms exercise training, endothelial function, flow-mediated dilation (FMD) and endothelial progenitor cells (EPCs). The 16 included studies provided a total of 529 participants, 293 in an intervention and 236 in controls groups. FMD was improved with exercise training in exercise vs. control, SMD of 1.08 (95%CI 0.70 to 1.46, ptraining improved endothelial function, assessed via FMD, and endothelial progenitor cells in heart failure patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  13. Role of Lipotoxicity in Endothelial Dysfunction

    OpenAIRE

    Kim, Jeong-a; Montagnani, Monica; Chandrasekran, Sruti; Quon, Michael J.

    2012-01-01

    Lipotoxicity, caused in large part by overnutrition, directly leads to endothelial dysfunction. Excess lipids in both the circulation and at the tissue level contribute to endothelial dysfunction that underlies much of the pathophysiology of both metabolic disease, including obesity and diabetes and their CV complications. Direct lipotoxic effects on other organs as well as secondary insults from endothelial dysfunction synergize to cause substantial morbidity and mortality. Lifestyle interve...

  14. Phenolic Molding Compounds

    Science.gov (United States)

    Koizumi, Koji; Charles, Ted; de Keyser, Hendrik

    Phenolic Molding Compounds continue to exhibit well balanced properties such as heat resistance, chemical resistance, dimensional stability, and creep resistance. They are widely applied in electrical, appliance, small engine, commutator, and automotive applications. As the focus of the automotive industry is weight reduction for greater fuel efficiency, phenolic molding compounds become appealing alternatives to metals. Current market volumes and trends, formulation components and its impact on properties, and a review of common manufacturing methods are presented. Molding processes as well as unique advanced techniques such as high temperature molding, live sprue, and injection/compression technique provide additional benefits in improving the performance characterisitics of phenolic molding compounds. Of special interest are descriptions of some of the latest innovations in automotive components, such as the phenolic intake manifold and valve block for dual clutch transmissions. The chapter also characterizes the most recent developments in new materials, including long glass phenolic molding compounds and carbon fiber reinforced phenolic molding compounds exhibiting a 10-20-fold increase in Charpy impact strength when compared to short fiber filled materials. The role of fatigue testing and fatigue fracture behavior presents some insight into long-term reliability and durability of glass-filled phenolic molding compounds. A section on new technology outlines the important factors to consider in modeling phenolic parts by finite element analysis and flow simulation.

  15. Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Santangelo, C.; Filesi, C.; Varì, R.; Scazzocchio, B.; Filardi, T.; Fogliano, V.; D’Archivio, M.; Giovannini, C.; Lenzi, A.; Morano, S.; Masella, R.

    2016-01-01

    Aim: Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic

  16. USING OF Agrobacterium-MEDIATED TRANSFORMATION FOR THE BIOTECHNOLOGICAL IMPROVEMENT OF COMPOSITAE PLANTS. ІІ. SYNTHESIS OF BIOACTIVE COMPOUNDS IN TRANSGENIC PLANTS AND «HAIRY» ROOTS

    Directory of Open Access Journals (Sweden)

    N. A. Matvieieva

    2015-04-01

    Full Text Available The review focused on the data concerning current state in the field of Compositae “hairy” roots and transgenic plants construction using A.tumefaciens- and A. rhizogenes-mediated transformation to obtain biologically active compounds, including recombinant proteins. The article presents data on the results of genetic transformation of Cichorium intybus, Lactuca sativa, Artemisia annua, Artemisia vulgaris, Calendula officinalis, Withania somnifera and other Compositae plants as well as studies on the artemisinin, flavonoids, polyphenols, fructans and other compounds accumulation in transgenic plants and roots. The data show that the use of biotechnological approaches for construction of "hairy" roots and transgenic plants with new features are of great interest. The possibility of increase in the accumulation of naturally synthesized bioactive compounds and recombinant proteins production via A. tumefaciens and A. rhizogenes-mediated transformation have been shown. In vitro cultivation of transgenic plants characterized by high level of bioactive compounds accumulation and synthesis of recombinant proteins makes it possible to obtain guaranteed pure raw material. Using of biotechnological approaches preserved natural populations of plants is particularly important for rare and endangered plant species.

  17. Fast Etching of Molding Compound by an Ar/O2/CF4 Plasma and Process Improvements for Semiconductor Package Decapsulation

    NARCIS (Netherlands)

    Tang, J.; Gruber, D.; Schelen, J.B.J.; Funke, H.J.; Beenakker, C.I.M.

    2012-01-01

    Decapsulation of a SOT23 semiconductor package with 23 um copper wire bonds is conducted with an especially designed microwave induced plasma system. It is found that a 30%-60% CF4 addition in the O2/CF4 etchant gas results in high molding compound etching rate. Si3N4 overetching which is

  18. Compound odontoma

    Directory of Open Access Journals (Sweden)

    Monica Yadav

    2012-01-01

    Full Text Available Odontomas have been extensively reported in the dental literature, and the term refers to tumors of odontogenic origin. Though the exact etiology is still unknown, the postulated causes include: local trauma, infection, inheritance and genetic mutation. The majority of the lesions are asymptomatic; however, may be accompanied with pain and swelling as secondary complaints in some cases. Here, we report a case of a compound odontome in a 14 year old patient.

  19. Ecscr regulates insulin sensitivity and predisposition to obesity by modulating endothelial cell functions.

    Science.gov (United States)

    Akakabe, Yoshiki; Koide, Masahiro; Kitamura, Youhei; Matsuo, Kiyonari; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Miyata, Keishi; Oike, Yuichi; Ikeda, Koji

    2013-01-01

    Insulin resistance is closely associated with obesity and is one of the earliest symptoms of type-2 diabetes. Endothelial cells are involved in the pathogenesis of insulin resistance through their role in insulin delivery and adipose tissue angiogenesis. Here we show that Ecscr (endothelial cell surface expressed chemotaxis and apoptosis regulator; also known as ARIA), the transmembrane protein that regulates endothelial cell signalling, is highly expressed in white and brown adipose tissues, and regulates energy metabolism and glucose homeostasis by modulating endothelial cell functions. Ecscr-deficient mice fed a normal chow show improved glucose tolerance and enhanced insulin sensitivity. We demonstrate that Ecscr deletion enhances the insulin-mediated Akt/endothelial nitric oxide synthase activation in endothelial cells, which increases insulin delivery into the skeletal muscle. Ecscr deletion also protects mice on a high-fat diet from obesity and obesity-related metabolic disorders by enhancing adipose tissue angiogenesis. Conversely, targeted activation of Ecscr in endothelial cells impairs glucose tolerance and predisposes mice to diet-induced obesity. Our results suggest that the inactivation of Ecscr enhances insulin sensitivity and may represent a new therapeutic strategy for treating metabolic syndrome.

  20. A novel mechanism of diabetic vascular endothelial dysfunction: Hypoadiponectinemia-induced NLRP3 inflammasome activation.

    Science.gov (United States)

    Zhang, Jinglong; Xia, Linying; Zhang, Fen; Zhu, Di; Xin, Chao; Wang, Helin; Zhang, Fuyang; Guo, Xian; Lee, Yan; Zhang, Ling; Wang, Shan; Guo, Xiong; Huang, Chong; Gao, Feng; Liu, Yi; Tao, Ling

    2017-06-01

    It has been well documented that hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. However, the exact molecular mechanism which mediates this process has not been fully described. The current study aimed to investigate the role of hypoadiponectinemia-induced NLRP3 inflammasome activation in diabetic vascular endothelial dysfunction and its molecular mechanism. Male adult adiponectin knockout mice and wild type mice were fed with a high fat diet to establish a type 2 diabetic mellitus model. In addition, human umbilical vein endothelial cells (HUVECs) were cultured and subjected to high glucose/high fat (HG/HF). The NLRP3 inflammasome activation was increased in type 2 diabetic mice and treatment of diabetic aortic segments with MCC950, a potent selective inhibitor of NLRP3 inflammasome ex vivo improved endothelial-dependent vasorelaxation. NLRP3 inflammasome activation and vascular endothelial injury were significantly increased in APN-KO mice compared with WT mice in diabetes and MCC950 decreased diabetic vascular endothelial dysfunction to comparable levels in APN-KO mice and WT mice. Adiponectin could decrease NLRP3 inflammasome activation and attenuate endothelial cell injury, which was abolished by NLRP3 inflammasome overexpression. Inhibition of peroxynitrite formation preferentially attenuated NLRP3 inflammasome activation in APN-KO diabetic mice. The current study demonstrated for the first time that hypoadiponectinemia-induced NLRP3 inflammasome activation was a novel mechanism of diabetic vascular endothelial dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hermann, Thomas S; Li, Weijie; Dominguez, Helena

    2005-01-01

    OBJECTIVE: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects...... and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism. METHODS: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation...... occlusion plethysmography. Gene expression was measured by real-time PCR. RESULTS: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0...

  2. Maternal biomarkers of endothelial dysfunction and preterm delivery.

    Directory of Open Access Journals (Sweden)

    Xinhua Chen

    Full Text Available Endothelial dysfunction is key to the development of atherosclerosis. Preterm delivery foreshadows later maternal cardiovascular disease (CVD, but it is not known if endothelial dysfunction also occurs. We prospectively measured circulating biomarkers of endothelial dysfunction in pregnant women with preterm or term delivery.We conducted a case-control study nested within a large prospective epidemiological study of young, generally healthy pregnant women. Women who delivered preterm (<37 completed weeks gestation, n = 240 and controls who delivered at term (n = 439 were included. Pregnancies complicated by preeclampsia were analyzed separately. Circulating endothelial dysfunction biomarkers included soluble intercellular adhesion molecule-1 (sICAM-1, vascular cell adhesion molecule-1 (sVCAM-1 and soluble E-selectin (sE-selectin.Elevated levels of sICAM-1 and sVCAM-1 were positively associated with preterm delivery independent of usual risk factors. At entry (∼16 wks, the adjusted odds ratio (AOR was 1.73 (95% confidence interval (CI 1.09-2.74 for the highest quartile of sICAM-1 versus the lowest quartile and for sVCAM-1 the AOR was 2.17 (95% CI 1.36-3.46. When analysis was limited to cases with a spontaneous preterm delivery, the results were unchanged. Similar results were obtained for the 3rd trimester (∼30 wks. Elevated sE-selectin was increased only in preterm delivery complicated by preeclampsia; risk was increased at entry (AOR 2.32, 95% CI 1.22-4.40 and in the 3rd trimester (AOR 3.37, 95% CI 1.78-6.39.Impaired endothelial function as indicated by increased levels of soluble molecules commonly secreted by endothelial cells is a pathogenic precursor to CVD that is also present in women with preterm delivery. Our findings underscore the need for follow-up studies to determine if improving endothelial function prevents later CVD risk in women.

  3. Nebivolol: impact on cardiac and endothelial function and clinical utility

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2012-03-01

    Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

  4. Imaging tumor endothelial marker 8 using an {sup 18}F-labeled peptide

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Qimeng [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Shanghai Jiaotong University, Department of Radiology, Shanghai First People' s Hospital, Shanghai (China); Yang, Min; Gao, Haokao; Zhu, Lei; Lin, Xin; Guo, Ning; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Zhang, Guixiang [Shanghai Jiaotong University, Department of Radiology, Shanghai First People' s Hospital, Shanghai (China); Eden, Henry S. [National Institutes of Health, Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Niu, Gang [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); National Institutes of Health, Imaging Sciences Training Program, Radiology and Imaging Sciences, Clinical Center and National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2011-10-15

    Tumor endothelial marker 8 (TEM8) has been reported to be upregulated in both tumor cells and tumor-associated endothelial cells in several cancer types. TEM8 antagonists and TEM8-targeted delivery of toxins have been developed as effective cancer therapeutics. The ability to image TEM8 expression would be of use in evaluating TEM8-targeted cancer therapy. A 13-meric peptide, KYNDRLPLYISNP (QQM), identified from the small loop in domain IV of protective antigen of anthrax toxin was evaluated for TEM8 binding and labeled with {sup 18}F for small-animal PET imaging in both UM-SCC1 head-and-neck cancer and MDA-MB-435 melanoma models. A modified ELISA showed that QQM peptide bound specifically to the extracellular vWA domain of TEM8 with an IC{sub 50} value of 304 nM. Coupling 4-nitrophenyl 2-{sup 18}F-fluoropropionate with QQM gave almost quantitative yield and a high specific activity (79.2 {+-} 7.4 TBq/mmol, n = 5) of {sup 18}F-FP-QQM at the end of synthesis. {sup 18}F-FP-QQM showed predominantly renal clearance and had significantly higher accumulation in TEM8 high-expressing UM-SCC1 tumors (2.96 {+-} 0.84 %ID/g at 1 h after injection) than TEM8 low-expressing MDA-MB-435 tumors (1.38 {+-} 0.56 %ID/g at 1 h after injection). QQM peptide bound specifically to the extracellular domain of TEM8. {sup 18}F-FP-QQM peptide tracer would be a promising lead compound for measuring TEM8 expression. Further efforts to improve the affinity and specificity of the tracer and to increase its metabolic stability are warranted. (orig.)

  5. Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

    Science.gov (United States)

    Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

    2016-03-01

    The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

  6. Improvement effect of corn silk, perilla leaf and grape stem extract mixture against UVB-induced skin damage and compound 48/80-induced pruritus

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Byoung Ok; Shin, Jae Young; Che, Denis Nchang; Hwang, Young Min; Lee, Hyun Seo; Choi, Ji Won; Jang, Seon Il [Jeonju University, Jeonju (Korea, Republic of); Ryu, Cheol [Hyangmiwon Corporation, Gimje (Korea, Republic of)

    2017-02-15

    This study was conducted to evaluate the synergistic protective effects of mixtures of corn silk, perilla leaf and grape stem extract (CPG mixture) against UVB-induced skin damage and compound 48/80-induced pruritus in mice. The results showed that treatment with CPG mixture exhibited much stronger suppressive effect on erythema and melanin index as well as melanin formation than treatment with ascorbic acid (AA) in UVB-irradiated mice. Moreover, the treatment with CPG mixture showed ameliorative effect on immune cell infiltration and collagen fiber destruction in UV-irradiated mice. The treatment with CPG mixture inhibited glutathione (GSH) depletion, lipid peroxidation and production of pro-inflammatory cytokines in UVB-irradiated mice. Furthermore, the treatment with CPG mixture inhibited compound 48/80-induced scratching behavior and histological changes in mice. Taken together, these results indicated that CPG mixture has potentials as functional and therapeutic materials against skin damage and itch-related skin diseases.

  7. Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

    Science.gov (United States)

    Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

    2015-07-15

    The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

  8. Protection by simvastatin on hyperglycemia-induced endothelial dysfunction through inhibiting NLRP3 inflammasomes.

    Science.gov (United States)

    Lv, Zhen-Huan; Phuong, Trinh Anh; Jin, Shi-Jie; Li, Xiao-Xue; Xu, Ming

    2017-10-31

    Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal elements to initiate inflammatory responses and plays an important role in the dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents vascular endothelial dysfunction from inflammasome invasion contributing to reduce cardiovascular risk. However, Whether or not the simvastatin improves vascular endothelial barrier function through inhibiting the activation of NLRP3 inflammasome pathway remains unknown. Here, we explored the role and mechanisms of simvastatin in the activation of NLRP3 inflammasome which are involved in vascular endothelial hyperpermeability causing by the disruption of tight junction protein ZO-1 and adherens junction protein VE-Cadherin, an early initiation of cardiovascular complication. Our results found that high glucose significantly induced the formation and activation of NLRP3 inflammasome through NADPH oxidase-dependent reactive oxygen species (ROS) formation, associated with vascular endothelial hyperpermeability causing by ZO-1 and VE-Cadherin disruption in the rat aortic endothelial cells (RAECs). Simvastatin treatment remarkably abolished vascular endothelial hyperpermeability and enhanced the protein expression of ZO-1 and VE-Cadherin through NLRP3 inflammasome. Mechanistically, the inhibitory role of simvastatin endothelial hyperpermeability is attributed to the decreased release of cytoplasmic high mobility group box protein-1 (HMGB1) derived from endothelial NLRP3 inflammasome activation. We further confirm the protective role of simvastatin on vascular leakage in the heart of diabetic rats injected with Evans blue dye, which was associated with HMGB1 release in the serum. Collectively, the mechanism of simvastatin treatment alleviating vascular endothelial permeability dysfunction may be through inhibiting the NLRP3 inflammasome-dependent HMGB1 release in RAECs.

  9. The Extrusion Process as an Alternative for Improving the Biological Potential of Sorghum Bran: Phenolic Compounds and Antiradical and Anti-Inflammatory Capacity

    Directory of Open Access Journals (Sweden)

    Norma Julieta Salazar Lopez

    2016-01-01

    Full Text Available Approximately 80% of sorghum phenolic compounds are linked to arabinoxylans by ester bonds, which are capable of resisting the digestion process in the upper gastrointestinal tract, compromising their bioaccessibility and biological potential. The aim of this study was to evaluate the effect of the extrusion process on the content of phenolic compounds in sorghum bran and its impact on phenolic compounds and antiradical and anti-inflammatory capacity. Results revealed that the extrusion process increased total phenol content in sorghum bran compared to nonextruded sorghum, particularly for extrusion at 180°C with 20% moisture content (2.0222±0.0157 versus 3.0729±0.0187 mg GAE/g +52%, which positively affected antiradical capacity measured by the DPPH and TEAC assays. The percentage of inhibition of nitric oxide (NO production by RAW cells due to the presence of extruded sorghum bran extract was significantly higher than that of nonextruded sorghum bran extract (90.2±1.9% versus 76.2±1.3%. The results suggest that extruded sorghum bran could be used as a functional ingredient and provide advantages to consumers by reducing diseases related to oxidative stress and inflammation.

  10. A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2017-11-01

    Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

  11. Mussel-inspired immobilization of vascular endothelial growth factor (VEGF) for enhanced endothelialization of vascular grafts.

    Science.gov (United States)

    Shin, Young Min; Lee, Yu Bin; Kim, Seok Joo; Kang, Jae Kyeong; Park, Jong-Chul; Jang, Wonhee; Shin, Heungsoo

    2012-07-09

    Most polymeric vascular prosthetic materials have low patency rate for replacement of small diameter vessels (polydopamine-mediated immobilization of growth factors on the surface of polymeric materials as a versatile tool to modify surface characteristics of vascular grafts potentially for accelerated endothelialization. Polydopamine was deposited on the surface of biocompatible poly(L-lactide-co-ε-caprolactone) (PLCL) elastomer, on which vascular endothelial growth factor (VEGF) was subsequently immobilized by simple dipping. Surface characteristics and composition were investigated by using scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Immobilization of VEGF on the polydopamine-deposited PLCL films was effective (19.8 ± 0.4 and 197.4 ± 19.7 ng/cm(2) for DPv20 and DPv200 films, respectively), and biotin-mediated labeling of immobilized VEGF revealed that the fluorescence intensity increased as a function of the concentration of VEGF solution. The effect of VEGF on adhesion of HUVECs was marginal, which may have been masked by polydopamine layer that also enhanced cell adhesion. However, VEGF-immobilized substrate significantly enhanced proliferation of HUVECs for over 7 days of in vitro culture and also improved their migration. In addition, immobilized VEGF supported robust cell to cell interactions with strong expression of CD 31 marker. The same process was effective for immobilization of basic fibroblast growth factor, demonstrating the robustness of polydopamine layer for secondary ligation of growth factors as a simple and novel surface modification strategy for vascular graft materials.

  12. Magnesium compounds

    Science.gov (United States)

    Kramer, D.A.

    2007-01-01

    Seawater and natural brines accounted for about 52 percent of U.S. magnesium compounds production in 2006. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties from well brines in Michigan. Caustic-calcined magnesia was recovered from sea-water by Premier Chemicals in Florida; from well brines in Michigan by Martin Marietta and Rohm and Haas; and from magnesite in Nevada by Premier Chemicals. Intrepid Potash-Wendover and Great Salt Lake Minerals recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from brucite by Applied Chemical Magnesias in Texas, from seawater by SPI Pharma in Delaware and Premier Chemicals in Florida, and by Martin Marietta and Rohm and Haas from their operations mentioned above. About 59 percent of the magnesium compounds consumed in the United States was used for refractories that are used mainly to line steelmaking furnaces. The remaining 41 percent was consumed in agricultural, chemical, construction, environmental and industrial applications.

  13. Endothelial progenitor cell dysfunction in diabetes mellitus

    NARCIS (Netherlands)

    Loomans, Cindy Johanna Maria

    2007-01-01

    Postnatally, Endothelial Progenitor Cells are needed to maintain the integrity of the endothelium (re-endothelialization) and to augment wound healing or vascularize hypoxic areas (neovascularization). Complex networks of different signals and regulators have been identified to be involved in these

  14. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...

  15. PPAR Gamma and Angiogenesis: Endothelial Cells Perspective

    Directory of Open Access Journals (Sweden)

    Jerzy Kotlinowski

    2016-01-01

    Full Text Available We summarize the current knowledge concerning PPARγ function in angiogenesis. We discuss the mechanisms of action for PPARγ and its role in vasculature development and homeostasis, focusing on endothelial cells, endothelial progenitor cells, and bone marrow-derived proangiogenic cells.

  16. Vitamin D Receptor Activation Mitigates the Impact of Uremia on Endothelial Function in the 5/6 Nephrectomized Rats

    Directory of Open Access Journals (Sweden)

    J. Ruth Wu-Wong

    2010-01-01

    Full Text Available Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD. This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation (−50.0±7.4% in NX rats versus −96.2±5.3% in SHAM at 30 μM acetylcholine. The endothelial-dependent relaxation was improved to –58.2±6.0%, –77.5±7.3%, and –90.5±4.0% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 μg/kg for two weeks, respectively, while paricalcitol at 0.042 μg/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.

  17. Antihypertensive methyldopa, labetalol, hydralazine, and clonidine reversed tumour necrosis factor-α inhibited endothelial nitric oxide synthase expression in endothelial-trophoblast cellular networks.

    Science.gov (United States)

    Xu, Bei; Bobek, Gabriele; Makris, Angela; Hennessy, Annemarie

    2017-03-01

    Medications used to control hypertension in pregnancy also improve trophoblast and endothelial cellular interaction in vitro. Tumour necrosis factor-α (TNF-α) inhibits trophoblast and endothelial cellular interactions and simultaneously decreases endothelial nitric oxide synthase (eNOS) expression. This study investigated whether antihypertensive medications improved these cellular interactions by modulating eNOS and inducible nitric oxide synthase (iNOS) expression. Human uterine myometrial microvascular endothelial cells (UtMVECs) were pre-incubated with (or without) low dose TNF-α (0.5 ng/mL) or TNF-α plus soluble fms-like tyrosine kinase-1 (sFlt-1) (100 ng/mL). The endothelial cells were cultured on Matrigel. After endothelial cellular networks appeared, trophoblast derived HTR-8/SVneo cells were co-cultured in the presence of clinically relevant doses of methyldopa, labetalol, hydralazine or clonidine for 24 hours. Cells were retrieved from the Matrigel to extract mRNA and eNOS and iNOS expression were examined by quantitative PCR. Methyldopa, labetalol, hydralazine and clonidine reversed the inhibitory effect of TNF-α on eNOS mRNA expression. After pre-incubating endothelial cells with TNF-α and sFlt-1, all the medications except methyldopa lost their effect on eNOS mRNA expression. In the absence of TNF-α, antihypertensive medications did not change eNOS expression. The mRNA expression of iNOS was not affected by TNF-α or any medications. This study shows that selected antihypertensive medications used in the treatment of hypertension in pregnancy increase eNOS expression in vitro when induced by the inflammatory TNF-α. The anti-angiogenic molecule sFlt-1 may antagonise the potential benefit of these medications by interfering with the NOS pathway. © 2016 John Wiley & Sons Australia, Ltd.

  18. Molecular expression in transfected corneal endothelial cells

    Science.gov (United States)

    Wang, Fan; Miao, Zhuang; Lu, Chengwei; Hao, Jilong

    2017-10-01

    To investigate the capability of human corneal endothelial cells serving as immunological cells. Expression of HLA-DP, -DQ, -DR, CD40, CD80, and CD86 was determined by immunohistochemical methods. Meanwhile, purified peripheral blood mononuclear cells were cocultured with human corneal endothelial cells which were pre-treated with and without -IFN respectively, activation of lymphocytes was determined by FACS analysis. In coculture system, T lymphocyte was activated by corneal endothelial cells, HLA-DP, -DQ, -DR and CD40 expression were increased by - IFN induction. Costimulatory molecular CD80 was shown on the endothelial cells. Human corneal endothelial cells were assumed to be involved in the corneal transplantation rejection process as potential antigen presenting cells.

  19. Evaluation of the Effects of Different Energy Drinks and Coffee on Endothelial Function.

    Science.gov (United States)

    Molnar, Janos; Somberg, John C

    2015-11-01

    Endothelial function plays an important role in circulatory physiology. There has been differing reports on the effect of energy drink on endothelial function. We set out to evaluate the effect of 3 energy drinks and coffee on endothelial function. Endothelial function was evaluated in healthy volunteers using a device that uses digital peripheral arterial tonometry measuring endothelial function as the reactive hyperemia index (RHI). Six volunteers (25 ± 7 years) received energy drink in a random order at least 2 days apart. Drinks studied were 250 ml "Red Bull" containing 80 mg caffeine, 57 ml "5-hour Energy" containing 230 mg caffeine, and a can of 355 ml "NOS" energy drink containing 120 mg caffeine. Sixteen volunteers (25 ± 5 years) received a cup of 473 ml coffee containing 240 mg caffeine. Studies were performed before drink (baseline) at 1.5 and 4 hours after drink. Two of the energy drinks (Red Bull and 5-hour Energy) significantly improved endothelial function at 4 hours after drink, whereas 1 energy drink (NOS) and coffee did not change endothelial function significantly. RHI increased by 82 ± 129% (p = 0.028) and 63 ± 37% (p = 0.027) after 5-hour Energy and Red Bull, respectively. The RHI changed after NOS by 2 ± 30% (p = 1.000) and by 7 ± 30% (p = 1.000) after coffee. In conclusion, some energy drinks appear to significantly improve endothelial function. Caffeine does not appear to be the component responsible for these differences. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Maize silk antibiotic polyphenol compounds and molecular genetic improvement of resistance to corn earworm (Helicoverpa zea Boddie) in sh2 sweet corn

    OpenAIRE

    Baozhu Guo; Ana Butrón; Brian T. Scully

    2010-01-01

    The flavor of sh2 super-sweet corn is preferred by consumers. Unfortunately, sh2 sweet corn has little genetic variation for insect resistance. In this paper we review the functions of two loci, p1 and a1. The P1 allele has a major role in sh2 sweet corn resistance to corn earworm, an allele that was lost in historical selection because of its pleiotropic effect on undesirable cob color and silk browning. The P1 allele has significant effects on biosyntheses of silk antibiotic compounds, mays...

  1. Magnesium compounds

    Science.gov (United States)

    Kramer, D.A.

    2012-01-01

    Seawater and natural brines accounted for about 57 percent of magnesium compounds produced in the United States in 2011. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties LLC from well brines in Michigan. Caustic-calcined magnesia was recovered from seawater by Premier Magnesia LLC in Florida, from well brines in Michigan by Martin Marietta and from magnesite in Nevada by Premier Magnesia. Intrepid Potash Wendover LLC and Great Salt Lake Minerals Corp. recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from seawater by SPI Pharma Inc. in Delaware and Premier Magnesia in Florida, and by Martin Marietta from its brine operation in Michigan.

  2. Bismaleimide compounds

    Science.gov (United States)

    Adams, Johnnie E.; Jamieson, Donald R.

    1986-01-14

    Bismaleimides of the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently is H, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, C1 or Br, or R.sub.1 and R.sub.2 together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R.sub.1 and R.sub.2 are not t-butyl or t-butoxy; X is O, S or Se; n is 1-3; and the alkylene bridging group, optionally, is substituted by 1-3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  3. SNAP23 Regulates Endothelial Exocytosis of von Willebrand Factor.

    Science.gov (United States)

    Zhu, Qiuyu Martin; Zhu, Qiuyu; Yamakuchi, Munekazu; Lowenstein, Charles J

    2015-01-01

    Endothelial exocytosis regulates vascular thrombosis and inflammation. The trafficking and release of endothelial vesicles is mediated by SNARE (Soluble NSF Attachment protein REceptors) molecules, but the exact identity of endothelial SNAREs has been unclear. Three SNARE molecules form a ternary complex, including isoforms of the syntaxin (STX), vesicle-associated membrane protein (VAMP), and synaptosomal-associated protein (SNAP) families. We now identify SNAP23 as the predominant endothelial SNAP isoform that mediates endothelial exocytosis of von Willebrand Factor (VWF). SNAP23 was localized to the plasma membrane. Knockdown of SNAP23 decreased endothelial exocytosis, suggesting it is important for endothelial exocytosis. SNAP23 interacted with the endothelial exocytic machinery, and formed complexes with other known endothelial SNARE molecules. Taken together, these data suggest that SNAP23 is a key component of the endothelial SNARE machinery that mediates endothelial exocytosis.

  4. Compounding in synthetic aperture imaging

    DEFF Research Database (Denmark)

    Hansen, J. M.; Jensen, J. A.

    2012-01-01

    A method for obtaining compound images using synthetic aperture data is investigated using a convex array transducer. The new approach allows spatial compounding to be performed for any number of angles without reducing the frame rate or temporal resolution. This important feature is an intrinsic...... property of how the compound images are constructed using synthetic aperture data and an improvement compared with how spatial compounding is obtained using conventional methods. The synthetic aperture compound images are created by exploiting the linearity of delay-and-sum beamformation for data collected...... from multiple spherical emissions to synthesize multiple transmit and receive apertures, corresponding to imaging the tissue from multiple directions. The many images are added incoherently, to produce a single compound image. Using a 192-element, 3.5-MHz, λ-pitch transducer, it is demonstrated from...

  5. Establishment of a porcine corneal endothelial organ culture model for research purposes.

    Science.gov (United States)

    Kunzmann, Berenike C; Hellwinkel, Olaf J C; Klameth, Christian; Wenzel, Daniel; Bartz-Schmidt, Karl U; Spitzer, Martin S; Schultheiss, Maximilian

    2017-10-27

    Human corneas usually are not available for research, as they are used for transplantation only. At the same time, scientific studies on cultured human endothelial cells can produce misleading results due to inevitable dedifferentiation. Therefore, an organ-culture model of porcine corneas-displaying endothelial cell death rates comparable to those of cultured human corneas-would be very desirable. Fresh pig eyes were prepared under sterile conditions to obtain corneoscleral buttons, corneal buttons and so called "split corneal buttons" (new preparation method) and cultivated for 15 days. Morphology of the endothelial cell layer was observed by light microscopy on day 1, 8 and 15. On day 15 staining with trypan blue and alizarin red S was performed. Photographs were evaluated in a randomized, blinded manner. Here, the morphology of the corneal endothelium and the number of endothelial cells per mm(2) were analyzed. After 15 days of cultivation the endothelial cell layer was maintained only in corneal buttons and split corneal buttons. Alizarin red S stained areas and the existence of polymorphisms like rosette figures and reformation figures were significantly less frequent in split corneal buttons than in corneal buttons. Loss of endothelial cells was significantly greater in corneal buttons [575 ± 25/250 cells/mm(2) (median ± 25%/75%-quantile); 14.8%] than in split corneal buttons [417 ± 138/179 cells/mm(2) (median ± 25%/75%-quantile); 10.2%]. The new preparation method of split corneal buttons allows the cultivation of porcine corneas for 2 weeks with cell death rates comparable to those of the corresponding human tissue in cornea banks without the need to add de-swelling additives to the media. This is therefore a simple and highly reliable method model to be applied in intervention studies on corneal endothelial cells in their natural compound.

  6. [Transplantation of corneal endothelial cells].

    Science.gov (United States)

    Amano, Shiro

    2002-12-01

    Though conventional corneal transplantation has achieved great success, it still has several drawbacks including limited availability of donor corneas, recurrent allograft rejection, and subsequent graft failure in certain cases. Reconstructing clinically usable corneas by applying the technology of regenerative medicine can offer a solution to these problems, as well as making corneal transplantation a non-emergency surgery and enabling the usage of banked corneal cells. In the present study, we focused on corneal endothelium that is critical for corneal transparency and investigated the reconstruction of cornea utilizing cultured human corneal endothelial cells (HCECs). We succeeded in steadily culturing HCECs by using culture dishes pre-coated with extracellular matrix produced by calf corneal endothelial cells and culture media that contained basic fibroblast growth factor and fetal bovine serum. We performed the following analysis utilizing these cultured HCECs. The older the donor was, the more frequently large senescent cells appeared in the passaged HCECs. The telomeres of HCECs were measured as terminal restriction fragments (TRF) by Southern blotting. HCECs, in vivo from donors in their seventies had a long TRFs of over 12 kilobases. Passaging shortened the TRFs but there was no difference in TRFs among donors of various ages. These results indicated that shortening of telomere length is not related to senescence of HCECs. We investigated the role of advanced glycation end products (AGEs) in the senescence of in vivo HCECs. The results indicated that AGE-protein in the aqueous humor is endocytosed into HCECs via AGE receptors expressed on the surface of HCECs and damages HCECs by producing reactive oxygen species and inducing apoptosis, suggesting that AGEs, at least partly, cause the senescence of HECEs. HCECs were cultured using adult human serum instead of bovine serum to get rid of bovine material that can be infected with prions. Primary and passage

  7. Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway.

    Science.gov (United States)

    Campelo, Adrián E; Cutini, Pablo H; Massheimer, Virginia L

    2012-04-01

    The aim of the present study was to investigate the effect of testosterone on the modulation of cellular events associated with vascular homeostasis. In rat aortic strips, 5-20 min treatment with physiological concentrations of testosterone significantly increased nitric oxide (NO) production. The rapid action of the steroid was suppressed by the presence of an androgen receptor antagonist (flutamide). We obtained evidence that the enhancement in NO synthesis was dependent on the influx of calcium from extracellular medium, because in the presence of a calcium channel blocker (verapamil) the effect of testosterone was reduced. Using endothelial cell (EC) cultures, we demonstrated that androgen directly acts at the endothelial level. Chelerythrine or PD98059 compound completely suppressed the increase in NO production, suggesting that the mechanism of action of the steroid involves protein kinase C and mitogen-activated protein kinase pathways. It is known that endothelial NO released into the vascular lumen serves as an inhibitor of platelet activation and aggregation. We showed that testosterone inhibited platelet aggregation and this effect was dependent on endothelial NO synthesis. Indeed, the enhancement of NO production elicited by androgen was associated with EC growth. The steroid significantly increased DNA synthesis after 24 h of treatment, and this mitogenic action was blunted in the presence of NO synthase inhibitor N-nitro-l-arginine methyl ester. In summary, testosterone modulates vascular EC growth and platelet aggregation through its direct action on endothelial NO production.

  8. Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors.

    Science.gov (United States)

    Goodman, Krista B; Bury, Michael J; Cheung, Mui; Cichy-Knight, Maria A; Dowdell, Sarah E; Dunn, Allison K; Lee, Dennis; Lieby, Jeffrey A; Moore, Michael L; Scherzer, Daryl A; Sha, Deyou; Suarez, Dominic P; Murphy, Dennis J; Harpel, Mark R; Manas, Eric S; McNulty, Dean E; Annan, Roland S; Matico, Rosalie E; Schwartz, Benjamin K; Trill, John J; Sweitzer, Thomas D; Wang, Da-Yuan; Keller, Paul M; Krawiec, John A; Jaye, Michael C

    2009-01-01

    Endothelial lipase (EL) activity has been implicated in HDL catabolism, vascular inflammation, and atherogenesis, and inhibitors are therefore expected to be useful for the treatment of cardiovascular disease. Sulfonylfuran urea 1 was identified in a high-throughput screening campaign as a potent and non-selective EL inhibitor. A lead optimization effort was undertaken to improve potency and selectivity, and modifications leading to improved LPL selectivity were identified. Radiolabeling studies were undertaken to establish the mechanism of action for these inhibitors, which were ultimately demonstrated to be irreversible inhibitors.

  9. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-10-01

    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  10. Dysfunctional Endothelial Progenitor Cells in Metabolic Syndrome

    Science.gov (United States)

    Devaraj, Sridevi; Jialal, Ishwarlal

    2012-01-01

    The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34+KDR+ phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS. PMID:21941528

  11. Preventive effect of l-carnitine and its derivatives on endothelial dysfunction and platelet aggregation.

    Science.gov (United States)

    Mohammadi, Mohammad; Hajhossein Talasaz, Azita; Alidoosti, Mohammad

    2016-10-01

    Oxidative stress plays an important role in platelet activation and endothelial dysfunction. Exogenous and endogenous reactive oxygen species are associated with platelet activation and vascular dysfunction. Antioxidants have been shown to attenuate oxidative stress and consequently endothelial dysfunction by preventing inflammation, regulating vascular tone, and promoting antiadhesive and antithrombotic properties. l-carnitine and its derivatives have been demonstrated to improve endothelial and platelet function against oxidative stress by several mechanisms, some of which cannot be found in other antioxidants. The role of l-carnitine and its derivatives in endothelial dysfunction and platelet activation will be reviewed here from the perspective of basic and clinical research. This study reviews in vitro and in vivo studies, clinical trials, and abstracts in the English language that have examined the protective effects of l-carnitine and its derivatives on endothelial dysfunction and platelet aggregation in pathological conditions. We searched experimental studies, clinical trials, and other review articles to obtain the materials. Although in vitro physiological models, animal studies on vascular and platelet function, and some human studies on these systems are in favor of the preventive effects of l-carnitine and its derivatives on endothelial dysfunction and platelet aggregation, more clinical trials are needed to clarify the clinical importance of l-carnitine as a supportive option to maintain the normal homeostatic function of the vasculature and to prevent platelet activation. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  12. Deep lamellar endothelial keratoplasty in the first United States patients: early clinical results.

    Science.gov (United States)

    Terry, M A; Ousley, P J

    2001-04-01

    To report the early clinical results of the first U.S. patients to undergo deep lamellar endothelial keratoplasty (DLEK) surgery for the treatment of endothelial dysfunction. Two patients with pseudophakia with Fuchs' endothelial dystrophy, under an Institutional Review Board-approved protocol, underwent replacement of the endothelium through a limbal, scleral pocket incision (DLEK). Their vision, pachymetry, and corneal map topography were measured in the early postoperative period and were compared with preoperative measurements. Both patients had improvement in all parameters within 1 month after surgery, and corneal topography showed no significant change from before the surgery. The first patient's vision at 6 months was 20/40 (+2) with a 0.75-diopter (D) decrease in astigmatism and a normal pachymetry of 573 microm. The second patient's vision at 6 months was 20/40 (-2) with a 0.25-D increase in astigmatism and a pachymetry of 618 microm. Graft endothelial cell counts at 6 months were 1,692 and 2,631 cells/mm2, respectively. The DLEK procedure, with its absence of corneal surface incisions and sutures, preserves the preoperative topography and demonstrates good donor endothelial cell count and function early in the postoperative period. If interface clarity can be maintained, the potential advantages over penetrating keratoplasty in the treatment of endothelial dysfunction are considerable.

  13. Role of Rutin on Nitric Oxide Synthesis in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Azizah Ugusman

    2014-01-01

    Full Text Available Nitric oxide (NO, produced by endothelial nitric oxide synthase (eNOS, is a major antiatherogenic factor in the blood vessel. Oxidative stress plays an important role in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Decreased availability of endothelial NO promotes the progression of endothelial dysfunction and atherosclerosis. Rutin is a flavonoid with multiple cardiovascular protective effects. This study aimed to investigate the effects of rutin on eNOS and NO production in cultured human umbilical vein endothelial cells (HUVEC. HUVEC were divided into four groups: control; oxidative stress induction with 180 μM H2O2; treatment with 300 μM rutin; and concomitant induction with rutin and H2O2 for 24 hours. HUVEC treated with rutin produced higher amount of NO compared to control (P<0.01. In the oxidative stress-induced HUVEC, rutin successfully induced cells’ NO production (P<0.01. Rutin promoted NO production in HUVEC by inducing eNOS gene expression (P<0.05, eNOS protein synthesis (P<0.01, and eNOS activity (P<0.05. Treatment with rutin also led to increased gene and protein expression of basic fibroblast growth factor (bFGF in HUVEC. Therefore, upregulation of eNOS expression by rutin may be mediated by bFGF. The results showed that rutin may improve endothelial function by augmenting NO production in human endothelial cells.

  14. Endothelialization of implanted cardiovascular biomaterial surfaces: the development from in vitro to in vivo.

    Science.gov (United States)

    Liu, Tao; Liu, Shihui; Zhang, Kun; Chen, Junying; Huang, Nan

    2014-10-01

    Restenosis and thrombosis formation after cardiovascular devices implantation continue to be problematic. Although various platforms and parameters of cardiovascular devices have been designed and optimized over the years, postoperative complications are hard to avoid. The native vascular endothelium always provide a nonthrombogenic surface as well as prevent intimal overproliferation, thereby, the presence of a confluent endothelial cell layer on material surfaces have been widely accepted as an ideal approach to improve the biocompatibility of implanted cardiovascular materials. Endothelialization on biomaterial surfaces is initially developed by in vitro cell seeding. However, numerous no-perfect parts of this method are existed for clinical use. The emergency of endothelial progenitor cells may provide a promising way for setting these limitations. Over the last decades, countless researches about EPCs-based in vivo induced self-endothelialization have been reported and mainly focused on cellular therapy, pharmacological therapy, materials designing, or surface biofunctional modification. This review details the development of endothelialization on cardiovascular material surfaces from in vitro to in vivo. Endothelialization progress on the basis of molecular biological level and bioinformatics theory is expected to be the key point in the coming decades. © 2013 Wiley Periodicals, Inc.

  15. Immortalized endothelial cell lines for in vitro blood-brain barrier models: A systematic review.

    Science.gov (United States)

    Rahman, Nurul Adhwa; Rasil, Alifah Nur'ain Haji Mat; Meyding-Lamade, Uta; Craemer, Eva Maria; Diah, Suwarni; Tuah, Ani Afiqah; Muharram, Siti Hanna

    2016-07-01

    Endothelial cells play the most important role in construction of the blood-brain barrier. Many studies have opted to use commercially available, easily transfected or immortalized endothelial cell lines as in vitro blood-brain barrier models. Numerous endothelial cell lines are available, but we do not currently have strong evidence for which cell lines are optimal for establishment of such models. This review aimed to investigate the application of immortalized endothelial cell lines as in vitro blood-brain barrier models. The databases used for this review were PubMed, OVID MEDLINE, ProQuest, ScienceDirect, and SpringerLink. A narrative systematic review was conducted and identified 155 studies. As a result, 36 immortalized endothelial cell lines of human, mouse, rat, porcine and bovine origins were found for the establishment of in vitro blood-brain barrier and brain endothelium models. This review provides a summary of immortalized endothelial cell lines as a guideline for future studies and improvements in the establishment of in vitro blood-brain barrier models. It is important to establish a good and reproducible model that has the potential for multiple applications, in particular a model of such a complex compartment such as the blood-brain barrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Oxidative stress effects on endothelial cells treated with different athletes' sera.

    Science.gov (United States)

    Conti, Valeria; Corbi, Graziamaria; Russomanno, Giusy; Simeon, Vittorio; Ferrara, Nicola; Filippelli, Walter; Limongelli, Francesco; Canonico, Raffaele; Grasso, Concetta; Stiuso, Paola; Dicitore, Alessandra; Filippelli, Amelia

    2012-01-01

    Exercise training is a nonpharmacological intervention that improves cardiovascular function and enhances endothelial homeostasis in patients with cardiovascular diseases. However, the amount of benefit achieved varies widely depending on the type and duration of exercise. Moreover, data about the long-term effects of physical activity are scarce. In this study, endothelial cells, exposed or not to oxidative stress, were conditioned with sera from athletes regularly participating in sports classified as "aerobic" (triathlon), "mixed aerobic-anaerobic" (soccer), and "anaerobic" (sprint running). Functional and hemodynamic variables did not differ between groups of athletes, whereas there were dramatic changes in serum markers for oxidative stress. Lipid peroxidation assessed by the thiobarbituric acid reactive substances assay and catalase activity were the lowest and nitric oxide availability was the highest in sera of triathletes. Endothelial cells cultured in serum from triathletes (T-endothelial cells) had the highest survival, evaluated by viability assay, BrdU incorporation, and senescence-associated β galactosidase assays, and preserved the endothelial appearance before and after stress in contrast to the cells grown in sera from the other athletes. T-endothelial cells also had the highest catalase messenger RNA expression and, after stress, the highest catalase activity of all the endothelial cells. Moreover, poststress activity of Sirt1, a NAD(+)-dependent deacetylase involved in cellular stress resistance and a key regulator of longevity, was significantly increased in T-endothelial cells. Different types of exercise training induced different molecular effects in terms of survival, morphology, and antioxidant system efficiency. The in vitro technique used herein may help to shed light on the molecular basis of effects of long-term physical activity in humans.

  17. FOXF1 maintains endothelial barrier function and prevents edema after lung injury.

    Science.gov (United States)

    Cai, Yuqi; Bolte, Craig; Le, Tien; Goda, Chinmayee; Xu, Yan; Kalin, Tanya V; Kalinichenko, Vladimir V

    2016-04-19

    Multiple signaling pathways, structural proteins, and transcription factors are involved in the regulation of endothelial barrier function. The forkhead protein FOXF1 is a key transcriptional regulator of embryonic lung development, and we used a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis, injury, and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1(-/-)) caused lung inflammation and edema, leading to respiratory insufficiency and death. Deletion of a single Foxf1 allele made heterozygous Pdgfb-iCreER/Foxf1(+/-)mice more susceptible to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells with homozygous FOXF1 deletion indicated reduced expression of genes critical for maintenance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, enhanced lung endothelial permeability, and increased the abundance of the mRNA and protein for sphingosine 1-phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assays demonstrated that FOXF1 directly bound to and induced the transcriptional activity of the S1pr1 promoter. Pharmacological administration of S1P to injured Pdgfb-iCreER/Foxf1(+/-)mice restored endothelial barrier function, decreased lung edema, and improved survival. Thus, FOXF1 promotes normal lung homeostasis and repair, in part, by enhancing endothelial barrier function through activation of the S1P/S1PR1 signaling pathway. Copyright © 2016, American Association for the Advancement of Science.

  18. Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Juan Pías-Peleteiro

    2017-01-01

    Full Text Available Intracerebral hemorrhage (ICH is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells (EPCs have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.

  19. Heterologous corneal endothelial cell transplantation--human corneal endothelial cell transplantation in Lewis rats.

    OpenAIRE

    Tchah, H.

    1992-01-01

    A heterologous corneal endothelial transplantation was attempted using human endothelial cells and a Lewis rat penetrating keratoplasty model. Cultured human endothelial cells were seeded to a Lewis rat cornea, which was denuded of its endothelium. When grafted into the syngeneic Lewis rat, the graft remained clear for at least five days, and then became opaque and edematous because of immune rejection reaction. In contrast, corneas denuded of their endothelium became opaque and edematous imm...

  20. Endothelial Nitric Oxide Synthase Uncoupling: A Novel Pathway in OSA Induced Vascular Endothelial Dysfunction

    OpenAIRE

    Varadharaj, Saradhadevi; Porter, Kyle; Pleister, Adam; Wannemacher, Jacob; Sow, Angela; Jarjoura, David; Zweier, Jay L.; Khayat, Rami N.

    2014-01-01

    The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2−·) and nitric oxide (NO) in the microcir...

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

    Science.gov (United States)

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

    2012-08-01

    The regenerative potential of endothelial progenitor cell (EPC)-based therapies is limited due to poor cell viability and minimal retention following application. Neovascularization can be improved by means of scaffolds supporting EPCs. The aim of the present study was to investigate whether human early EPCs (eEPCs) could be efficiently cultured on pharmacologically active microcarriers (PAMs), made with poly(d,l-lactic-coglycolic acid) and coated with adhesion/extracellular matrix molecules. They may serve as a support for stem cells and may be used as cell carriers providing a controlled delivery of active protein such as the angiogenic factor, vascular endothelial growth factor-A (VEGF-A). eEPC adhesion to fibronectin-coated PAMs (FN-PAMs) was assessed by means of microscopic evaluation and by means of Alamar blue assay. Phospho ERK(1/2) and PARP-1 expression was measured by means of Western blot to assess the survival effects of FN-PAMs releasing VEGF-A (FN-VEGF-PAMs). The Alamar blue assay or a modified Boyden chamber assay was employed to assess proliferative or migratory capacity, respectively. Our data indicate that eEPCs were able to adhere to empty FN-PAMs within a few hours. FN-VEGF-PAMs increased the ability of eEPCs to adhere to them and strongly supported endothelial-like phenotype and cell survival. Moreover, the release of VEGF-A by FN-PAMs stimulated in vitro HUVEC migration and proliferation. These data strongly support the use of PAMs for supporting eEPC growth and survival and for stimulating resident mature human endothelial cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Effects of cognate, non-cognate and synthetic CXCR4 and ACKR3 ligands on human lung endothelial cell barrier function.

    Directory of Open Access Journals (Sweden)

    You-Hong Cheng

    indicate that CXCR4 activation attenuates thrombin-induced lung endothelial barrier function impairment and suggest that protective effects of CXCL12 are dictated by its CXCR4 agonist activity and interactions of distinct protein moieties with heparan sulfate on the endothelial surface. These data may facilitate development of compounds with improved pharmacological properties to attenuate thrombin-induced vascular leakage in the pulmonary circulation.

  3. Abnormal Corneal Endothelial Maturation in Collagen XII and XIV Null Mice

    Science.gov (United States)

    Hemmavanh, Chinda; Koch, Manuel; Birk, David E.; Espana, Edgar M.

    2013-01-01

    Purpose. Maturation of the endothelium and the adjacent matrix was characterized in wild-type (WT) mice. The influence of FACIT collagen XII and XIV deficiency on the morphology, maturation, and function of the corneal endothelium was examined. Methods. Analysis of the endothelium and Descemet's membrane (DM) was performed using transmission electron microscopy at postnatal day (P)4, P14, and P30 in WT, Col12a1−/−, Col14a1−/−, and Col12a1−/−/Col14a1−/− mice. Endothelial junctions were analyzed using ZO-1. The presence of endothelial–stromal communications was evaluated with phalloidin staining as well as electron microscopy. Finally, corneal thickness was assessed. Results. A thin DM, clefts between endothelial cells and DM, and large “vacuole-like” structures were present in the endothelial cells of WT mice at P4 but not noted at P30. The endothelia of Col12a1−/−, Col14a1−/−, and compound Col12a1−/−/Col14a1−/− in the P30 cornea maintained the vacuole-like structures seen at P4. A mature endothelial junction pattern was delayed in the null corneas. Expression of ZO-1 in WT endothelia at P14 was diffuse and localized to the basolateral and apical cell membrane. At P30, staining was localized to intercellular junctions. ZO-1 reactivity was patchy in Col12a1−/−, Col14a1−/−, and compound Col12a1−/−/Col14a1−/− corneas at P14 and P30. Stromal thickness was increased in P30 null corneas. Endothelial cell processes were demonstrated penetrating the DM and into the underlying stroma, throughout the entire endothelial layer in the P4 cornea. Conclusions. Collagen XII and XIV null mice demonstrate delayed endothelial maturation. The structural alterations suggest functional changes in endothelial function resulting in increased corneal thickness. Endothelial–stromal interactions suggest a pathway for signal transduction. PMID:23599329

  4. Nitride coating enhances endothelialization on biomedical NiTi shape memory alloy.

    Science.gov (United States)

    Ion, Raluca; Luculescu, Catalin; Cimpean, Anisoara; Marx, Philippe; Gordin, Doina-Margareta; Gloriant, Thierry

    2016-05-01

    Surface nitriding was demonstrated to be an effective process for improving the biocompatibility of implantable devices. In this study, we investigated the benefits of nitriding the NiTi shape memory alloy for vascular stent applications. Results from cell experiments indicated that, compared to untreated NiTi, a superficial gas nitriding treatment enhanced the adhesion of human umbilical vein endothelial cells (HUVECs), cell spreading and proliferation. This investigation provides data to demonstrate the possibility of improving the rate of endothelialization on NiTi by means of nitride coating. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Development of novel arginase inhibitors for therapy of endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Jochen eSteppan

    2013-09-01

    Full Text Available Endothelial dysfunction and resulting vascular pathology have been identified as an early hallmark of multiple diseases, including diabetes mellitus. One of the major contributors to endothelial dysfunction is a decrease in nitric oxide (NO bioavailability, impaired NO signaling and an increase in the amount of reactive oxygen species (ROS. In the endothelium NO is produced by eNOS (endothelial nitric oxide synthase, for which L-arginine is a substrate. Arginase, an enzyme critical in the urea cycle also metabolizes L-arginine, thereby directly competing with eNOS for their common substrate and constraining its bioavailability for eNOS, thereby compromising NO production. Arginase expression and activity is upregulated in many cardiovascular diseases including ischemia reperfusion injury, hypertension, atherosclerosis, and diabetes mellitus. More importantly, since the 1990s, specific arginase inhibitors such as N-hydroxy-guanidinium or N-hydroxy-nor-L-arginine, and boronic acid derivatives, such as, 2(S-amino-6-boronohexanoic acid, and S-(2-boronoethyl-L-cysteine (BEC, that can bridge the binuclear manganese cluster of arginase have been developed. These highly potent and specific inhibitors can now be used to probe arginase function and thereby modulate the redox milieu of the cell by changing the balance between NO and ROS. Inspired by this success, drug discovery programs have recently led to the identification of α-α-disubstituted amino acid based arginase inhibitors (such as (R-2-amino-6-borono-2-(2-(piperidin-1-ylethylhexanoic acid, that are currently under early investigation as therapeutics. Finally, some investigators concentrate on identification of plant derived compounds with arginase inhibitory capability, such as piceatannol-3'-O-β-D-glucopyranoside (PG. All of these synthesized or naturally derived small molecules may represent novel therapeutics for vascular disease particularly that associated with diabetes.

  6. Leukocytes Breach Endothelial Barriers by Insertion of Nuclear Lobes and Disassembly of Endothelial Actin Filaments

    Directory of Open Access Journals (Sweden)

    Sagi Barzilai

    2017-01-01

    Full Text Available The endothelial cytoskeleton is a barrier for leukocyte transendothelial migration (TEM. Mononuclear and polymorphonuclear leukocytes generate gaps of similar micron-scale size when squeezing through inflamed endothelial barriers in vitro and in vivo. To elucidate how leukocytes squeeze through these barriers, we co-tracked the endothelial actin filaments and leukocyte nuclei in real time. Nuclear squeezing involved either preexistent or de novo-generated lobes inserted into the leukocyte lamellipodia. Leukocyte nuclei reversibly bent the endothelial actin stress fibers. Surprisingly, formation of both paracellular gaps and transcellular pores by squeezing leukocytes did not require Rho kinase or myosin II-mediated endothelial contractility. Electron-microscopic analysis suggested that nuclear squeezing displaced without condensing the endothelial actin filaments. Blocking endothelial actin turnover abolished leukocyte nuclear squeezing, whereas increasing actin filament density did not. We propose that leukocyte nuclei must disassemble the thin endothelial actin filaments interlaced between endothelial stress fibers in order to complete TEM.

  7. Hausa verbal compounds

    NARCIS (Netherlands)

    McIntyre, Joseph Anthony

    2006-01-01

    Verbal compounds abound in Hausa (a Chadic language). A very broad definition of Hausa verbal compounds (henceforth: VC) is “a compound with a verb”. Four types of verbal compound are analysed: V[erb]+X compounds, PAC+V compounds (a PAC is a pronoun complex indicating TAM), VCs with a ma prefix

  8. In vitro biocompatibility of sheath-core cellulose-acetate-based electrospun scaffolds towards endothelial cells and platelets.

    Science.gov (United States)

    Rubenstein, David A; Venkitachalam, Subramaniam M; Zamfir, Dan; Wang, Fang; Lu, Hongbing; Frame, Mary D; Yin, Wei

    2010-01-01

    Typically, tissue-engineered scaffolds mimic the topographical properties of the native extracellular matrix. However, other physical properties, such as the scaffold mechanical stiffness, are not imitated. The purpose of this study was to fabricate scaffolds with improved mechanical properties and investigate their biocompatibility towards endothelial cells and platelets. To enhance mechanical properties, an electrospinning apparatus was developed that fabricates fibers with sheath-core morphologies. Different combinations of cellulose acetate and chitosan were chosen to modulate the mechanical properties of the formed fibers. We hypothesized that mechanically stiffer scaffolds would improve endothelial cell growth and that all scaffolds would be compatible towards endothelial cells and platelets. Endothelial cell-culture conditions were quantified up to 5 days. Migration onto scaffolds was monitored for 10 days. Platelet aggregation, antagonized by thrombin receptor agonist peptide 6, was measured after scaffold incubation. A platelet activation time-course was assessed with the modified prothrombinase assay. As scaffold mechanical stiffness increased, endothelial cell growth within and adhesion to and migration throughout the scaffolds was promoted. Also, scaffolds did not induce platelet aggregation or activation. These results indicate that the mechanical stiffness of engineered scaffolds regulates endothelial cell-culture parameters and that these sheath-core electrospun scaffolds are compatible towards endothelial cells and platelets.

  9. Organic neem compounds inhibit soft-rot fungal growth and improve the strength of anthracite bricks bound with collagen and lignin for use in iron foundry cupolas.

    Science.gov (United States)

    Kelsey, D J; Nieto-Delgado, C; Cannon, F S; Brennan, R A

    2015-07-01

    To examine organic neem compounds for their effective growth inhibition of saprotrophic soft-rot fungi on anthracite bricks bound with collagen and lignin for use in iron foundry cupolas as an alternative fuel source. Azadirachtin, crude neem oil (NO), and clarified neem oil extract (CNO) were combined with copper to inhibit the growth of the soft-rot fungus, Chaetomium globosum. A synergistic interaction was observed between CNO and a low dose of copper on nutrient media (two-factor anova with triplicate replication: P strength. The effective collagen strength of the briquettes was enhanced by applying CNO to their surface prior to inoculation: the room temperature UC strength of the briquettes was 28 ± 4·6% greater when CNO (0·4 mg cm(-2) ) was surface-applied, and was 43 ± 3·0% greater when CNO plus copper (0·14 μg cm(-2) ) were surface-applied. Surface application of CNO and copper synergistically prevents fungal growth on bindered anthracite briquettes and increases their room temperature strength. This novel organic fungicidal treatment may increase the storage and performance of anthracite bricks in iron foundries, thereby saving 15-20% of the energy used in conventional coke production. © 2015 The Society for Applied Microbiology.

  10. Bioactive compounds during storage of fresh-cut spinach: the role of endogenous ascorbic acid in the improvement of product quality.

    Science.gov (United States)

    Bottino, Antonella; Degl'Innocenti, Elena; Guidi, Lucia; Graziani, Giulia; Fogliano, Vincenzo

    2009-04-08

    Spinach is rich in bioactive constituents such as vitamin C, flavonoids and phenolic acids. In this work, the biochemical modifications occurring during one week of storage at 4 degrees C were evaluated both in intact and in fresh-cut spinach. Results showed that vitamin C concentration is less affected by storage in fresh-cut spinach with respect to intact spinach. MS/MS analysis showed that the main flavonoids are not modified during storage in intact leaves, while some of them increased significantly during storage in the fresh-cut samples. Fresh-cut spinach did not show color alteration even if PPO activity increased significantly during storage. This finding was related to the high ascorbic acid content, which delays the subsequent polymerization events. This finding was confirmed by the unaltered concentration of phenolic compounds in fresh-cut spinach during storage. In conclusion, data about nutritional content and visual performance concurrently suggest that spinach is a suitable species for marketing as a fresh-cut product.

  11. Freeze-thaw method improves the detection of volatile compounds in insects using Headspace Solid-Phase Microextraction (HS-SPME)

    Science.gov (United States)

    Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC-MS) is commonly used in analyzing insect volatiles. In order to improve the detection of volatiles in insects, a freeze-thaw method was applied to insect samples before the HS-SPME-GC-MS analysis. ...

  12. Biophysical Cueing and Vascular Endothelial Cell Behavior

    Directory of Open Access Journals (Sweden)

    Joshua A. Wood

    2010-03-01

    Full Text Available Human vascular endothelial cells (VEC line the vessels of the body and are critical for the maintenance of vessel integrity and trafficking of biochemical cues. They are fundamental structural elements and are central to the signaling environment. Alterations in the normal functioning of the VEC population are associated with a number of vascular disorders among which are some of the leading causes of death in both the United States and abroad. VECs attach to their underlying stromal elements through a specialization of the extracellular matrix, the basement membrane. The basement membrane provides signaling cues to the VEC through its chemical constituents, by serving as a reservoir for cytoactive factors and through its intrinsic biophysical properties. This specialized matrix is composed of a topographically rich 3D felt-like network of fibers and pores on the nano (1–100 nm and submicron (100–1,000 nm size scale. The basement membrane provides biophysical cues to the overlying VECs through its intrinsic topography as well as through its local compliance (relative stiffness. These biophysical cues modulate VEC adhesion, migration, proliferation, differentiation, and the cytoskeletal signaling network of the individual cells. This review focuses on the impact of biophysical cues on VEC behaviors and demonstrates the need for their consideration in future vascular studies and the design of improved prosthetics.

  13. A lubricating compound

    Energy Technology Data Exchange (ETDEWEB)

    Barchan, G.P.; Alekseyenko, V.A.; Bolotnikov, V.S.; Burlov, A.S.; Chigarenko, G.G.; Kogan, V.A.

    1982-01-01

    In a lubricating compound (SK), which contains petroleum or synthetic oil, a complex ether (SE) and an additive (Pr), in order to improve the loading, antifriction and antiwear properties, a complex ether of glycerin of the formula C/sub 3/H/sub 5/R/sub 3/, where R is C/sub 3/H/sub 7/C00, C/sub 17/H/sub 33/C00, is used and 2-(n-tololsulfamino)benzalaniline is used as the additive. The ratio of components in percent is: 2-(n-tololsulfamino)benzalanaline, 0.1 to 0.4; complex ether, 20 to 30 and petroleum or synthetic oil to 100. Oils of different chemical structure and physical and chemical properties are used for making the lubricating compound: vaseline, medicinal, industrial, instrumental MVP, vacuum VM-4 and polyethylsiloxane liquid 132-25. The oil is mixed with the complex ether and additive in the cited proportions with heating to 100 degrees C and intensive mixing. After cooling it is ready for use. The results of tests of the proposed lubricating compound in a facial friction machine for lubricating friction subasemblies of steel and a copper alloy showed significant improvements in properties.

  14. Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea.

    Science.gov (United States)

    Khalyfa, Abdelnaby; Kheirandish-Gozal, Leila; Khalyfa, Ahamed A; Philby, Mona F; Alonso-Álvarez, María Luz; Mohammadi, Meelad; Bhattacharjee, Rakesh; Terán-Santos, Joaquin; Huang, Lei; Andrade, Jorge; Gozal, David

    2016-11-01

    Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells. To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status. Obese children (body mass index z score >1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cell-substrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays. Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children

  15. Cataract phacoemulsification and corneal endothelial cell damage

    Directory of Open Access Journals (Sweden)

    Ni Zhu

    2013-07-01

    Full Text Available Phacoemulsification with small incision, reduced number of inflammation cells, and better postoperative recovery has been recognized as the world's most popular option for cataract surgery. Modern cataract surgery is developing gradually from sight rehabilitating to refractive surgery with better vision acuity. Being the most important part of the eye refractive system, maintenance of the cornea's transparency relies heavily upon the healthy endothelial cells. It is well known that there will be endothelial cell loss after phacoemulsification and the damage of the endothelial cells may lead to corneal swellings and opacity, or even the corneal descompensation, which often severely influenced the postoperative vision recovery. This is a review of phacoemulsification and the risk factors of corneal endothelial damage pre-and postoperation.

  16. Apicobasal polarity of brain endothelial cells.

    Science.gov (United States)

    Worzfeld, Thomas; Schwaninger, Markus

    2016-02-01

    Normal brain homeostasis depends on the integrity of the blood-brain barrier that controls the access of nutrients, humoral factors, and immune cells to the CNS. The blood-brain barrier is composed mainly of brain endothelial cells. Forming the interface between two compartments, they are highly polarized. Apical/luminal and basolateral/abluminal membranes differ in their lipid and (glyco-)protein composition, allowing brain endothelial cells to secrete or transport soluble factors in a polarized manner and to maintain blood flow. Here, we summarize the basic concepts of apicobasal cell polarity in brain endothelial cells. To address potential molecular mechanisms underlying apicobasal polarity in brain endothelial cells, we draw on investigations in epithelial cells and discuss how polarity may go awry in neurological diseases. © The Author(s) 2015.

  17. Bacteria and endothelial cells: a toxic relationship.

    Science.gov (United States)

    Lubkin, Ashira; Torres, Victor J

    2017-02-01

    Pathogenic bacteria use the bloodstream as a highway for getting around the body, and thus have to find ways to enter and exit through the endothelium. Many bacteria approach this problem by producing toxins that can breach the endothelial barrier through diverse creative mechanisms, including directly killing endothelial cells (ECs), weakening the cytoskeleton within ECs, and breaking the junctions between ECs. Toxins can also modulate the immune response by influencing endothelial biology, and can modulate endothelial function by influencing the response of leukocytes. Understanding these interactions, in both the in vitro and in vivo contexts, is of critical importance for designing new therapies for sepsis and other severe bacterial diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Specular Microscopic Features of Corneal Endothelial Vacuolation

    Directory of Open Access Journals (Sweden)

    Mozhgan Rezaei Kanavi

    2011-01-01

    Full Text Available Purpose: To introduce a specular microscopic reference image for endothelial vacuolation in donated corneas. Methods: Two corneas from a donor with diffuse, round to oval dark areas at the endothelial level on slit lamp biomicroscopy and one normal-appearing donor cornea underwent specular microscopy, histopathologic evaluation and transmission electron microscopy. Results: Specular microscopy of the two corneas with abnormal-looking endothelium revealed large numbers of dark, round to oval structures within the endothelium in favor of endothelial vacuolation. Light microscopy disclosed variable sized cyst-like structures within the cytoplasm. Transmission electron microscopy showed electronlucent and relatively large-sized intracytoplasmic vacuoles. These features were not observed in the endothelium of the normal cornea. Conclusion: The specular microscopic features of endothelial vacuolation in donated corneas were confirmed by light microscopy and transmission electron microscopy, therefore the specular image may be proposed as a reference to eye banks.

  19. Study of intracellular signaling pathways triggered by natural antioxidants in human endothelial cells

    OpenAIRE

    Cossu, Annalisa

    2012-01-01

    Cardiovascular (CV) benefits of Natural Antioxidant (NA) supplementation are contradictory. Endothelial Cells (EC) are pivotal player on CV diseases onset/progression and thus represent a good model to study the NA impact on vascular pathophysiology. We show that two NA, coumaric acid and resveratrol, affect intracellular ROS levels and cell physiology in human EC. While at lower doses both compounds were antioxidant, at mildly high doses they became pro-oxidant, eliciting cell death by apopt...

  20. Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence.

    Science.gov (United States)

    Malavolta, Marco; Costarelli, Laura; Giacconi, Robertina; Basso, Andrea; Piacenza, Francesco; Pierpaoli, Elisa; Provinciali, Mauro; Ogo, Ogo A; Ford, Dianne

    2017-12-01

    Endothelial cell senescence and Zn nutritional status influence cardiovascular disease. The influence of Zn appears dichotomous, hence it is imperative to understand the relationship with cellular senescence to improve knowledge about the molecular and cellular basis of the disease. Here we aimed to determine: 1) the impact of chronic exposure to a moderately high dose of Zn on senescence of endothelial cells; 2) the changes in Zn homeostasis during the lifespan of primary cultured endothelial cells; and 3) the susceptibility of proliferating and senescent endothelial cells to cell death after short term exposure to increasing doses of Zn and of the Zn chelator TPEN. Chronic exposure to Zn accelerated senescence and untreated cells at later passages, where doubling time had increased, displayed relocation of labile Zn and altered expression of genes involved in the response to Zn toxicity, including SLC30A1, SLC39A6, SLC30A5, SLC30A10 and metallothioneins, indicating that senescent cells have altered zinc homeostasis. Most Zn-dependent genes that were expressed differently between early and late passages were correlated with changes in the expression of anti-apoptotic genes. Short-term treatment with a high dose of Zn leads to cell death, but only in the population of cells at both earlier and later passages that had already entered senescence. In contrast, Zn depletion led to death of cells at earlier but not later passages, which suggests that there are sub-populations of senescent cells that are resistant to Zn depletion. This resistant senescent cell population may accumulate under conditions of Zn deficiency and contribute to vascular pathology. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. [Endothelial dysfunction in pathogenesis of duodenal ulcer].

    Science.gov (United States)

    Oparin, A G; Oparin, A A

    2002-01-01

    It is shown that in patients with ulcer associated with Helicobacter pylori (HP) there is a close correlation between the severity of the lesion of gastroduodenal protective mucous barrier and that of endothelial dysfunction manifesting in elevated level of endothelin-1, serum levels of TBK-active products, inhibition of blood flow and narrowing of the celiac trunk. The correlation becomes stronger with expanding contamination of gastroduodenal mucosa with HP. Thus, HP may participate in breaking the protective mucous barrier in endothelial dysfunction.

  2. Endothelial microparticles: Sophisticated vesicles modulating vascular function

    Science.gov (United States)

    Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

    2015-01-01

    Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

  3. Endothelial dysfunction in hypertension: pathophysiological mechanism or marker of cardiovascular risk?

    Directory of Open Access Journals (Sweden)

    Lorenzo Ghiadoni

    2013-03-01

    Full Text Available Introduction Vascular endothelial production of nitric oxide (NO plays an important role in the modulation of vessel tone and structure, protecting the vascular wall from atherosclerosis. In pathological conditions, however, the endothelium also produces pro-atherogenic substances (mainly reactive oxygen species, which inactivate NO. The Endothelial dysfunction, induced by reduced NO availability, is known to contribute to the development and progression of vascular damage. For this reason, endothelial function has been a major focus of cardiovascular research in the last few decades. Because NO has a very short half-life and its in vivo measurement is difficult, many researchers prefer to measure its biological activity, particularly the NO-dependent vasodilation, at the level of the coronary and peripheral circulation by endothelial stimuli. The most widely used technique involves measurement of brachial artery flow-mediated dilation. This test allows non-invasive evaluation of endothelium-dependent vasodilation in the peripheral macrocirculation induced by a mechanical stimulus (increase in shear stress caused by 5 minutes of forearm ischemia. The vasodilatatory response is reduced in the presence of major cardiovascular risk factors, particularly essential hypertension. Conclusions Studies conducted mainly in high-risk patients have demonstrated that endothelial dysfunction within the coronary or peripheral circulation is predictive of cardiovascular events (independently of classical risk factors. Drug therapy can improve endothelial function by increasing the availability of NO (a possible adjunctive benefit in terms of preventing vascular damage and improving the prognosis. Future studies will establish whether the evaluation of endothelial function by non-invasive, standardized, reproducible, low-cost techniques is an important test for cardiovascular risk stratification in clinical practice.

  4. Endothelial Dysfunction in Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Curtis M. Steyers

    2014-06-01

    Full Text Available Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD. As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α, reactive oxygen species, oxidized LDL (low density lipoprotein, autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.

  5. Nitride coating enhances endothelialization on biomedical NiTi shape memory alloy

    Energy Technology Data Exchange (ETDEWEB)

    Ion, Raluca [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Luculescu, Catalin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, P.O. Box MG-36, 077125 Magurele-Bucharest (Romania); Cimpean, Anisoara, E-mail: anisoara.cimpean@bio.unibuc.ro [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Marx, Philippe [AMF Company, Route de Quincy, 18120 Lury-sur-Arnon (France); Gordin, Doina-Margareta; Gloriant, Thierry [INSA Rennes, UMR CNRS 6226 ISCR, 20 Avenue des Buttes de Coësmes, 35708 Rennes Cedex 7 (France)

    2016-05-01

    Surface nitriding was demonstrated to be an effective process for improving the biocompatibility of implantable devices. In this study, we investigated the benefits of nitriding the NiTi shape memory alloy for vascular stent applications. Results from cell experiments indicated that, compared to untreated NiTi, a superficial gas nitriding treatment enhanced the adhesion of human umbilical vein endothelial cells (HUVECs), cell spreading and proliferation. This investigation provides data to demonstrate the possibility of improving the rate of endothelialization on NiTi by means of nitride coating. - Highlights: • Gas nitriding process of NiTi is competent to promote cell spreading. • Surface nitriding of NiTi is able to stimulate focal adhesion formation and cell proliferation. • Similar expression pattern of vWf and eNOS was exhibited by bare and nitrided NiTi. • Gas nitriding treatment of NiTi shows promise for better in vivo endothelialization.

  6. Endothelialization of Novel Magnesium-Rare Earth Alloys with Fluoride and Collagen Coating

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2014-03-01

    Full Text Available Magnesium (Mg alloys are promising scaffolds for the next generation of cardiovascular stents because of their better biocompatibility and biodegradation compared to traditional metals. However, insufficient mechanical strength and high degradation rate are still the two main limitations for Mg materials. Hydrofluoric acid (HF treatment and collagen coating were used in this research to improve the endothelialization of two rare earth-based Mg alloys. Results demonstrated that a nanoporous film structure of fluoride with thickness of ~20 µm was formed on the Mg material surface, which improved the corrosion resistance. Primary human coronary artery endothelial cells (HCAECs had much better attachment, spreading, growth and proliferation (the process of endothelialization on HF-treated Mg materials compared to bare- or collagen-coated ones.

  7. Gene expression microarray data from human microvascular endothelial cells supplemented with a low concentration of niacin

    Directory of Open Access Journals (Sweden)

    Jennifer M. Hughes-Large

    2016-03-01

    Full Text Available The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors “Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity” (Hughes-Large et al. 2014. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, NAP1L2, and OR13C8 was confirmed by real time quantitative PCR.

  8. Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Chang-Jiang, E-mail: panchangjiang@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China); Pang, Li-Qun [Department of General Surgery, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an 223300 (China); Gao, Fei [Zhejiang Zylox Medical Devices Co., Ltd., Hangzhou 310000 (China); Wang, Ya-Nan; Liu, Tao; Ye, Wei; Hou, Yan-Hua [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China)

    2016-06-01

    Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents. - Highlights: • Heparin-loaded graphene oxide coating was

  9. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    Science.gov (United States)

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  10. Reduced Ang2 expression in aging endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  11. Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review.

    Science.gov (United States)

    Agbalalah, Tari; Hughes, Stephen F; Freeborn, Ellen J; Mushtaq, Sohail

    2017-10-01

    This systematic review aims to evaluate randomised controlled trials (RCTs) investigating the effect of vitamin D supplementation on endothelial function and inflammation in adults. An electronic search of published randomised controlled trials, using Cochrane, Pubmed and Medline databases was conducted, with the search terms related to vitamin D and endothelial function. Inclusion criteria were RCTs in adult humans with a measure of vitamin D status using serum/plasma 25(OH)D and studies which administered the intervention through the oral route. Among the 1107 studies retrieved, 29 studies met the full inclusion criteria for this systematic review. Overall, 8 studies reported significant improvements in the endothelial/inflammatory biomarkers/parameters measured. However, in 2 out of the 8 studies, improvements were reported at interim time points, but improvements were absent post-intervention. The remaining 21 trial studies did not show significant improvements in the markers of interest measured. Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults, results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters. This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. Improved provincial emission inventory and speciation profiles of anthropogenic non-methane volatile organic compounds: a case study for Jiangsu, China

    Science.gov (United States)

    Zhao, Yu; Mao, Pan; Zhou, Yaduan; Yang, Yang; Zhang, Jie; Wang, Shekou; Dong, Yanping; Xie, Fangjian; Yu, Yiyong; Li, Wenqing

    2017-06-01

    Non-methane volatile organic compounds (NMVOCs) are the key precursors of ozone (O3) and secondary organic aerosol (SOA) formation. Accurate estimation of their emissions plays a crucial role in air quality simulation and policy making. We developed a high-resolution anthropogenic NMVOC emission inventory for Jiangsu in eastern China from 2005 to 2014, based on detailed information of individual local sources and field measurements of source profiles of the chemical industry. A total of 56 NMVOCs samples were collected in nine chemical plants and were then analyzed with a gas chromatography - mass spectrometry system (GC-MS). Source profiles of stack emissions from synthetic rubber, acetate fiber, polyether, vinyl acetate and ethylene production, and those of fugitive emissions from ethylene, butanol and octanol, propylene epoxide, polyethylene and glycol production were obtained. Various manufacturing technologies and raw materials led to discrepancies in source profiles between our domestic field tests and foreign results for synthetic rubber and ethylene production. The provincial NMVOC emissions were calculated to increase from 1774 Gg in 2005 to 2507 Gg in 2014, and relatively large emission densities were found in cities along the Yangtze River with developed economies and industries. The estimates were larger than those from most other available inventories, due mainly to the complete inclusion of emission sources and to the elevated activity levels from plant-by-plant investigation in this work. Industrial processes and solvent use were the largest contributing sectors, and their emissions were estimated to increase, respectively, from 461 to 958 and from 38 to 966 Gg. Alkanes, aromatics and oxygenated VOCs (OVOCs) were the most important species, accounting for 25.9-29.9, 20.8-23.2 and 18.2-21.0 % to annual total emissions, respectively. Quantified with a Monte Carlo simulation, the uncertainties of annual NMVOC emissions vary slightly through the years

  13. Improved provincial emission inventory and speciation profiles of anthropogenic non-methane volatile organic compounds: a case study for Jiangsu, China

    Directory of Open Access Journals (Sweden)

    Y. Zhao

    2017-06-01

    Full Text Available Non-methane volatile organic compounds (NMVOCs are the key precursors of ozone (O3 and secondary organic aerosol (SOA formation. Accurate estimation of their emissions plays a crucial role in air quality simulation and policy making. We developed a high-resolution anthropogenic NMVOC emission inventory for Jiangsu in eastern China from 2005 to 2014, based on detailed information of individual local sources and field measurements of source profiles of the chemical industry. A total of 56 NMVOCs samples were collected in nine chemical plants and were then analyzed with a gas chromatography – mass spectrometry system (GC-MS. Source profiles of stack emissions from synthetic rubber, acetate fiber, polyether, vinyl acetate and ethylene production, and those of fugitive emissions from ethylene, butanol and octanol, propylene epoxide, polyethylene and glycol production were obtained. Various manufacturing technologies and raw materials led to discrepancies in source profiles between our domestic field tests and foreign results for synthetic rubber and ethylene production. The provincial NMVOC emissions were calculated to increase from 1774 Gg in 2005 to 2507 Gg in 2014, and relatively large emission densities were found in cities along the Yangtze River with developed economies and industries. The estimates were larger than those from most other available inventories, due mainly to the complete inclusion of emission sources and to the elevated activity levels from plant-by-plant investigation in this work. Industrial processes and solvent use were the largest contributing sectors, and their emissions were estimated to increase, respectively, from 461 to 958 and from 38 to 966 Gg. Alkanes, aromatics and oxygenated VOCs (OVOCs were the most important species, accounting for 25.9–29.9, 20.8–23.2 and 18.2–21.0 % to annual total emissions, respectively. Quantified with a Monte Carlo simulation, the uncertainties of annual NMVOC emissions

  14. Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

    Directory of Open Access Journals (Sweden)

    Qin Yang

    2014-01-01

    Full Text Available Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

  15. Endothelial toxicity of unusual nucleotide metabolites.

    Science.gov (United States)

    Pelikant-Malecka, Iwona; Sielicka, Alicja; Kaniewska, Ewa; Smolenski, Ryszard T; Slominska, Ewa M

    2015-08-01

    Endothelium plays a pivotal role in the vascular tone regulation, platelet aggregation, regulation of immune response, inflammation and angiogenesis and its dysfunction is an earliest event in the development of cardiovascular disease. All these processes are affected by endothelial dysfunction. Endothelial toxicity induced by metabolites present in blood is a common scenario in pathology. This involves physiological metabolites such as asymmetric dimethylarginine or homocysteine that are normally excreted by kidneys, but accumulate in pathological conditions, adversely affecting function of endothelium. Our group identified new molecule with potential endothelial toxicity: 4-pirydone-3-carboxamide-1-β-d-ribonucleoside (4PYR). This nucleoside is most likely produced by oxidation of nicotinamide containing precursor by aldehyde oxidase. 4PYR easy crosses cell membrane and become phosphorylated inside the cell giving rise to mono-, di- and triphospates (4PYMP, 4PYDP and 4PYTP). There is considerable evidence that 4PYR is toxic in endothelium and other cell types by disrupting cell energetics evident as ATP depletion. Endothelial dysfunction in the in vitro and in vivo experiments is, however, evident only after prolonged exposure to 4PYR while acute cardiovascular effects are minor. 4PYR endothelial toxicity could be particularly important in patients with chronic renal disease where accumulation of 4PYR and its metabolites is particularly prominent. 4PYR metabolism and toxicity could be blocked by application of nucleoside transport inhibitors and we have proven efficiency of such intervention. We believe that blocking metabolism of endothelial nucleoside toxins such as 4PYR could become important strategy for endothelial targeted therapy. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.

  16. Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications

    Directory of Open Access Journals (Sweden)

    Miroslav Radenkovic

    2016-01-01

    Full Text Available The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.

  17. Monomeric CXCL12 outperforms its dimeric and wild type variants in the promotion of human endothelial progenitor cells' function.

    Science.gov (United States)

    Chang, Shuang; Li, Yaning; Yuan, Fang; Qu, Meijie; Song, Yaying; Zhang, Zhijun; Yang, Guo-Yuan; Wang, Yongting

    2017-06-24

    CXCL12 overexpression improves neurobehavioral recovery during post-ischemic stroke through multiple mechanisms including promoting endothelial progenitor cells function in animal models. It has been proposed that the monomer and dimer forms possess differential chemotactic and regulatory function. The aim of present study is to explore whether a monomeric or dimeric CXCL12 plays a different role in the endothelial progenitor cells proliferation, migration, and tube-formation in vitro. In this study, we transferred monomeric, dimeric and wild type CXCL12 gene into endothelial progenitor cells via lentiviral vectors. We investigated endothelial progenitor cells function following the interaction of CXCL12/CXCR4 or CXCL12/CXCR7 and downstream signaling pathways. Our results showed that the monomeric CXCL12 transfected endothelial progenitor cells had enhanced ability in cell proliferation, migration, and tube-formation compared to that in dimeric or wild type controls (p function of migration, but not proliferation or tube-formation, was significantly reduced in the monomeric CXCL12 transfected endothelial progenitor cells when the cells were pre-treated with either CXCR4 inhibitor AMD3100 or siCXCR7 (p function was partially regulated by CXCL12/CXCR4 and CXCL12/CXCR7 signal pathways. Our study demonstrated that monomeric CXCL12 was the fundamental form, which played important roles in endothelial progenitor cells' proliferation, migration, and tube-formation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Direct surface modification of metallic biomaterials via tyrosine oxidation aiming to accelerate the re-endothelialization of vascular stents.

    Science.gov (United States)

    Kakinoki, Sachiro; Takasaki, Kensuke; Mahara, Atsushi; Ehashi, Tomo; Hirano, Yoshiaki; Yamaoka, Tetsuji

    2018-02-01

    Rapid in-situ re-endothelialization of coronary stents is one of the most effective approaches to inhibit late thrombosis and restenosis. Strut surfaces allowing excellent adhesion and migration of endothelial cells and endothelial progenitor cells may accelerate in-situ re-endothelialization. Here, a well-known endothelial cell adhesive peptide, Arg-Glu-Asp-Val (REDV), was directly immobilized onto metallic surfaces by means of single-step tyrosine oxidation with copper chloride (II) and hydrogen peroxide, which we recently reported as a new biomaterial modification technique. REDV immobilization on a 316L stainless steel plate improved endothelial cell adhesion and effectively suppressed platelet adhesion in vitro. In addition, a Co-Cr stent immobilized with Ac-Tyr-Gly-Gly-Gly-Arg-Glu-Asp-Val (Y-REDV) was implanted into a rabbit abdominal aorta. On 7 days postimplantation, 80% of the strut surface of the Y-REDV-immobilized stent was covered by a thin neointimal layer and was similar in appearance to native endothelium. Restenosis and late thrombosis were not observed in the Y-REDV-immobilized stent for 42 days. These findings suggest that direct immobilization of Y-REDV peptide onto metallic biomaterials by tyrosine oxidation is effective for promoting in-situ re-endothelialization in vascular stents. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 491-499, 2018. © 2017 Wiley Periodicals, Inc.

  19. A lubricating compound

    Energy Technology Data Exchange (ETDEWEB)

    Barchan, G.P.; Boltnikov, V.S.; Bulgarevich, A.F.; Chigarenko, G.G.; Ponomarenko, A.G.

    1982-01-01

    In a known lubricating compound (SK) in order to improve the loading, antifriction and antiwear properties, a dicarbonic acid of a complex ether of azelaic acid of the formula (CH/sub 2/)/sub 7/(COOC/sub 2/H/sub 2//sub n+1/)/sub 2/, where n = 4 to 8, is additionally introduced as a complex ether (SE). 1-(2-oxy-1-naphthylazo)-2-naphthol-4-sulfo acid is introduced as an additive. The ratio of components in percent is: 1-(2-oxy-1-naphthylazo)-2-naphthol-4-sulfo acid 0.1 to 0.5 and complex ether, 20 to 30 and petroleum or synthetic oil (Ms) to 100 percent. Synthetic or petroleum oil of varying chemical structure and physical and chemical properties is used to prepare the lubricating compound: industrialnoye-20, vaseline, industrialnoye-50, instrumental MPV, vacuum MV-4 and polytehylsiloxanic liquid 32 to 25. The oil is mixed with the complex ether and the additive in the cited ratios with heating to 100 degrees and intensive mixing. After cooling, an oil ready for use is produced. The lubricating properties of the lubricating compound are studied in a facial friction (Tr) machine with a movable sample of St45.

  20. Effect of lactated Ringer's solution and compound electrolyte solution on the corneal endothelium in phacoemulsification

    Directory of Open Access Journals (Sweden)

    Yang Xia

    2017-11-01

    Full Text Available AIM: To compare the effect of compound electrolyte solution and lactated Ringer's solution on corneal function in cataract phacoemulsification, and to provide scientific basis for clinical selection of appropriate perfusion fluid. METHODS: The patients with senile cataract were randomly divided into control group with lactated Ringer's solution as anterior chamber perfusion and experimental group with compound electrolyte as anterior chamber perfusion. Surgical removal of cataract and phacoemulsification with intraocular lens implantation were taken. The corneal endothelial cell density, central corneal thickness, hexagonal cell ratio and endothelial cell coefficient of variation were measured at preoperative and postoperative points. RESULTS: Totally 60 patients successfully completed all follow-ups, the experimental group of 30 cases, the control group of 30 cases. The density of corneal endothelial cells in experimental group was significantly higher than those in the lactated Ringer's solution group at 1 and 3d after operations(P=0.030, 0.046. The coefficient of variation of corneal endothelial cells in lactated Ringer's solution group was higher than that in compound electrolyte group at 1 and 14d after operation(P=0.025, 0.014. The visual acuity of the compound electrolyte group was better than that of the lactated Ringer's solution on the first day after operation(P=0.04. CONCLUSION: In the phacoemulsification of senile cataract, the compound electrolyte perfusion has better histocompatibility, which can maintain the stability of corneal endothelial cell structure and reduce corneal endothelial cell injury. The compound electrolyte perfusion solution is more suitable for senile cataract phacoemulsification surgery.

  1. Growth hormone-releasing peptide ghrelin inhibits homocysteine-induced endothelial dysfunction in porcine coronary arteries and human endothelial cells.

    Science.gov (United States)

    Hedayati, Nasim; Annambhotla, Suman; Jiang, Jun; Wang, Xinwen; Chai, Hong; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2009-01-01

    effect in the porcine coronary artery by blocking Hcy-induced endothelial dysfunction, improving eNOS expression, and reducing oxidative stress. Ghrelin also shows a protective effect on HCACEs from the Hcy-induced decrease in eNOS protein levels. The effect of ghrelin is receptor-dependent. Thus, ghrelin administration may have beneficial effects in the treatment of vascular disease in patients with hyperhomocysteinemia.

  2. EFFECT OF VITAMIN C AND VITAMIN E ON SUCROSE INDUCED ENDOTHELIAL DAMAGE IN RATS

    Directory of Open Access Journals (Sweden)

    Yisel González-Madariaga

    2017-12-01

    Full Text Available Endothelial damage may contribute to the atheriosclerosis development. Chronic sucrose intake could lead to the establishment of endothelial damage due to the increase of oxygen reactive species. Although antioxidants vitamins may be useful to improve the endothelium injury, more experimental designs are required. In the current study, Vitamin C and E were used with the purpose of evaluating the regression degree of the endothelial damage produced in an induced model by a sucrose-rich diet in Wistar rats. Four groups were formed (n=6. The endothelium damage was achieved by a 35% of sucrose intake during 18 weeks. Then, the vitamins were supplied for four weeks at 10 mg/kg. Endothelial dysfuntion were assessed by two indirect methods: Histopathological evaluation of abdominal aorta and the quantification of plasmatic endothelial cells. Some biochemical and biometric parameters were also determined. It was observed that both vitamins decreased the plasmatic endothelial cells, being Vitamin C the one with the highest reduction percentage (78.7 % vs 34.8 %. Both vitamin treatments decreased hyperlypemia and the gain of body weight. The histologic analysis of the abdominal aortic fragments showed a significant regression of the endothelium injury parameters; no-organization of elastic fibers and small clear vacuoles spread or fusioned in the cellular cytoplasm.The most improved morphometric parameter was wall thickness: 67.16 ±12.34 µm for vitamin C and 76.28 ± 18.0 µm for vitamin E vs 95.16 ± 42.09 µm for group without treatment (p<0.001. It is concluded that either Vitamin C or E may improve the endothelium injury provoked by the chronic supply of sucrose

  3. The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes.

    Science.gov (United States)

    Bagg, W; Ferri, C; Desideri, G; Gamble, G; Ockelford, P; Braatvedt, G D

    2001-11-01

    The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 +/- 0.25%; UC, 10.23 +/- 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.

  4. Endothelial monolayer permeability under controlled oxygen tension.

    Science.gov (United States)

    Funamoto, Kenichi; Yoshino, Daisuke; Matsubara, Kento; Zervantonakis, Ioannis K; Funamoto, Kiyoe; Nakayama, Masafumi; Masamune, Jun; Kimura, Yoshitaka; Kamm, Roger D

    2017-06-19

    Endothelial permeability has been extensively investigated in the context of pathologies such as cancer and also in studies of drug delivery from the circulation. Hypoxia is a critical regulator of endothelial cell (EC) behavior and affects the barrier function of endothelial linings, yet its role has been little studied. This paper reveals the effect of hypoxia on the permeability of an EC monolayer by cellular experiments using a microfluidic device and a conventional cell culture dish. Human umbilical vein endothelial cells (HUVECs) were seeded into one microfluidic channel, creating an EC monolayer on each vertical surface of a collagen gel confined to a central chamber. Oxygen tension was regulated to produce normoxic (21% O2) or hypoxic (3% O2) conditions by the supply of gas mixtures of oxygen, carbon dioxide, and nitrogen at predefined ratios into channels fabricated into the device. Permeability of the EC monolayer quantified by analyzing diffusion of fluorescence-labelled dextrans into the collagen gel increases with barrier function loss by 6 hour hypoxic exposure, showing 11-fold and 4-fold increases for 70 kDa and 10 kDa dextrans, respectively, on average. Consistent with this, subsequent immunofluorescent staining and separate western blot analysis of HUVECs on a culture dish demonstrate loose cell-cell adhesion resulting from internalization of VE-cadherin under hypoxia. Thus, hypoxic stress increases endothelial permeability by altering cell-cell junction integrity.

  5. Dietary phosphorus acutely impairs endothelial function.

    Science.gov (United States)

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  6. [Assessment of endothelial function in autoimmune diseases].

    Science.gov (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. Endothelial Extracellular Vesicles-Promises and Challenges.

    Science.gov (United States)

    Hromada, Carina; Mühleder, Severin; Grillari, Johannes; Redl, Heinz; Holnthoner, Wolfgang

    2017-01-01

    Extracellular vesicles, including exosomes, microparticles, and apoptotic bodies, are phospholipid bilayer-enclosed vesicles that have once been considered as cell debris lacking biological functions. However, they have recently gained immense interest in the scientific community due to their role in intercellular communication, immunity, tissue regeneration as well as in the onset, and progression of various pathologic conditions. Extracellular vesicles of endothelial origin have been found to play a versatile role in the human body, since they are on the one hand known to contribute to cardiovascular diseases, but on the other hand have also been reported to promote endothelial cell survival. Hence, endothelial extracellular vesicles hold promising therapeutic potential to be used as a new tool to detect as well as treat a great number of diseases. This calls for clinically approved, standardized, and efficient isolation and characterization protocols to harvest and purify endothelial extracellular vesicles. However, such methods and techniques to fulfill stringent requirements for clinical trials have yet to be developed or are not harmonized internationally. In this review, recent advances and challenges in the field of endothelial extracellular vesicle research are discussed and current problems and limitations regarding isolation and characterization are pointed out.

  8. Mixed Compound of DCPTA and CCC Increases Maize Yield by Improving Plant Morphology and Up-Regulating Photosynthetic Capacity and Antioxidants.

    Directory of Open Access Journals (Sweden)

    Yongchao Wang

    treatments. Compared to control, the bending strength of 3rd internode was increased by 14.47% in PCH-treated plants in 2011, increased by 18.40% in 2012,