Vascular endothelial growth factor-B promotes in vivo angiogenesis.


:Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B167 or with rhVEGF-A165. After 14 days, cell ingrowth in the Matrigel plug was increased by 2.0- and 2.5-fold in rhVEGF-B167-treated and rhVEGF-A165-treated mice, respectively (P<0.01), in association with a raise in phospho-Akt/Akt (1.8-fold, P<0.01) and endothelial NO synthase (eNOS) (1.80- and 1.60-fold, respectively; P<0.05) protein levels measured by Western blot. VEGF-B-induced cell ingrowth was impaired by treatment with NOS inhibitor (NG-nitro-l-arginine methyl ester; L-NAME, 10 mg/kg per day). Treatment with neutralizing antibody directed against the VEGF-B receptor VEGF-R1 (anti-VEGFR1, 10 microg) completely abrogated VEGF-B-related effects. Proangiogenic effect of VEGF-B was confirmed in a mouse model of surgically induced hindlimb ischemia. Plasmids containing human form of VEGF-A (phVEGF-A165) or VEGF-B (phVEGF-B167 or phVEGF-B186) were administered by in vivo electrotransfer. Angiographic score at day 28 showed significant improvement in ischemic/nonischemic leg ratio by 1.4- and 1.5-fold in mice treated with phVEGF-B167 and phVEGF-B186, respectively (P<0.05). Laser Doppler perfusion data also evidenced a 1.5-fold increase in phVEGF-B167-treated and phVEGF-B186-treated mice (P<0.05). Such an effect was associated with an upregulation of phospho-Akt/Akt and eNOS protein levels in the ischemic legs and was hampered by treatment with anti-VEGFR1. This study demonstrates for the first time that VEGF-B, in part through its receptor VEGF-R1, promotes angiogenesis in association with an activation of Akt and eNOS-related pathways.


Circ Res


Circulation research


Silvestre JS,Tamarat R,Ebrahimian TG,Le-Roux A,Clergue M,Emmanuel F,Duriez M,Schwartz B,Branellec D,Lévy BI




Has Abstract


2003-07-25 00:00:00














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    abstract:RATIONALE:Activated nuclear factor (NF)-κB signaling in the vascular endothelium promotes the initiation and progression of atherosclerosis. Targeting endothelial NF-κB may provide a novel strategy to limit chronic inflammation. OBJECTIVE:To examine the role of microRNA-181b (miR-181b) in endothelial NF-κB signaling a...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Sun X,He S,Wara AKM,Icli B,Shvartz E,Tesmenitsky Y,Belkin N,Li D,Blackwell TS,Sukhova GK,Croce K,Feinberg MW

    更新日期:2014-01-03 00:00:00

  • Relationship Between the Efficacy of Cardiac Cell Therapy and the Inhibition of Differentiation of Human iPSC-Derived Nonmyocyte Cardiac Cells Into Myofibroblast-Like Cells.

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    abstract::Heme oxygenase (HO)-1 is a protective antioxidant enzyme that prevents cardiomyocyte apoptosis, for instance, during progressive cardiomyopathy. Here we identify a fundamental aspect of the HO-1 protection mechanism by demonstrating that HO-1 activity in mouse heart stimulates the bigenomic mitochondrial biogenesis pr...

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    authors: Piantadosi CA,Carraway MS,Babiker A,Suliman HB

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  • Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy.

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    pub_type: 杂志文章


    authors: Zhou J,Ahmad F,Parikh S,Hoffman NE,Rajan S,Verma VK,Song J,Yuan A,Shanmughapriya S,Guo Y,Gao E,Koch W,Woodgett JR,Madesh M,Kishore R,Lal H,Force T

    更新日期:2016-04-15 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: McDonough JL,Arrell DK,Van Eyk JE

    更新日期:1999-01-08 00:00:00

  • Multiple types of Ca2+ currents in single canine Purkinje cells.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Tseng GN,Boyden PA

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    pub_type: 杂志文章


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    更新日期:2015-07-03 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Tamura T,Fronek A

    更新日期:1990-07-01 00:00:00

  • Heteromultimeric Kv1 channels contribute to myogenic control of arterial diameter.

    abstract::Inhibition of vascular smooth muscle (VSM) delayed rectifier K+ channels (K(DR)) by 4-aminopyridine (4-AP; 200 micromol/L) or correolide (1 micromol/L), a selective inhibitor of Kv1 channels, enhanced myogenic contraction of rat mesenteric arteries (RMAs) in response to increases in intraluminal pressure. The molecula...

    journal_title:Circulation research

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    authors: Plane F,Johnson R,Kerr P,Wiehler W,Thorneloe K,Ishii K,Chen T,Cole W

    更新日期:2005-02-04 00:00:00

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    journal_title:Circulation research

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    authors: Zhou Y,Mitra S,Varadharaj S,Parinandi N,Zweier JL,Flavahan NA

    更新日期:2006-06-09 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ishikawa T,Li LM,Shinmi O,Kimura S,Yanagisawa M,Goto K,Masaki T

    更新日期:1991-10-01 00:00:00

  • The role of acyltransferases in fatty acid utilization.

    abstract::Glycerophosphate and carnitine as competing acyl acceptors and the oxidation of different long chain acylcarnitines in isolated mitochondria have been investigated. In the presence of low concentrations of palmitate, glycerophosphate is the preferred acyl acceptor in isolated liver mitochondria, indicating that the gl...

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    pub_type: 杂志文章


    authors: Borrebaek B,Christiansen R,Christophersen BO,Bremer J

    更新日期:1976-05-01 00:00:00

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    authors: Bennett BM,Schröder H,Hayward LD,Waldman SA,Murad F

    更新日期:1988-10-01 00:00:00

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    authors: Elias RM,Wandolo G,Ranadive NS,Eisenhoffer J,Johnston MG

    更新日期:1990-11-01 00:00:00

  • Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein.

    abstract::In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680...

    journal_title:Circulation research

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    authors: North AJ,Brannon TS,Wells LB,Campbell WB,Shaul PW

    更新日期:1994-07-01 00:00:00

  • Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy.

    abstract::Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these...

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    pub_type: 杂志文章,评审


    authors: Manabe I,Shindo T,Nagai R

    更新日期:2002-12-13 00:00:00

  • Duration and Life-Stage of Antibiotic Use and Risks of All-Cause and Cause-Specific Mortality: Prospective Cohort Study.

    abstract::Rationale: The overuse of antibiotics has been an important clinical issue, and antibiotic exposure is linked to alterations in gut microbiota, which has been related to risks of various chronic diseases such as cardiovascular disease and cancer. Also, duration of antibiotic exposure may be a risk factor of premature ...

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    authors: Heianza Y,Ma W,Li X,Cao Y,Chan AT,Rimm EB,Hu FB,Rexrode KM,Manson JE,Qi L

    更新日期:2020-01-31 00:00:00

  • Endothelin 1 enhances myofilament Ca2+ responsiveness in aequorin-loaded ferret myocardium.

    abstract::The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of b...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Wang JX,Paik G,Morgan JP

    更新日期:1991-09-01 00:00:00

  • Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E.

    abstract::Oxidative stress has been suggested to potentiate atherogenesis. However, studies that have investigated the effect of antioxidants on atherosclerosis showed inconsistent results, ie, atherosclerosis was either retarded or not changed by dietary antioxidants. This report directly examined the effect of overexpressing ...

    journal_title:Circulation research

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    authors: Yang H,Roberts LJ,Shi MJ,Zhou LC,Ballard BR,Richardson A,Guo ZM

    更新日期:2004-11-26 00:00:00

  • Membrane potential fluctuations and transient inward currents induced by reactive oxygen intermediates in isolated rabbit ventricular cells.

    abstract::The cellular basis of reactive oxygen intermediate-induced arrhythmias was investigated in isolated rabbit ventricular cells using the whole-cell voltage- and current-clamp techniques. Singlet oxygen and superoxide were generated by the photoactivation of rose bengal. Single ventricular cells exposed to rose bengal (1...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Matsuura H,Shattock MJ

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  • Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice.

    abstract::We have recently demonstrated that endogenous erythropoietin (Epo)/Epo receptor (EpoR) system plays an important protective role in hypoxia-induced pulmonary hypertension. However, it remains to be examined whether vascular EpoR system contributes to angiogenesis in response to ischemia. We examined angiogenesis in Ep...

    journal_title:Circulation research

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    authors: Nakano M,Satoh K,Fukumoto Y,Ito Y,Kagaya Y,Ishii N,Sugamura K,Shimokawa H

    更新日期:2007-03-16 00:00:00

  • Central nervous system mechanisms involved in inhibition of renal sympathetic nerve activity induced by arginine vasopressin.

    abstract::Previous studies have suggested that intravenous infusion of arginine vasopressin (AVP) inhibits sympathetic nerve activity (SNA) in rabbits by its action at the brainstem. This study aimed to determine, first, whether this action of AVP depended on functioning baroreflex mechanisms. The second aim was to determine th...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Suzuki S,Takeshita A,Imaizumi T,Hirooka Y,Yoshida M,Ando S,Nakamura M

    更新日期:1989-11-01 00:00:00

  • Role of heart and lung receptors with nonmedullated vagal afferents in circulatory control.

    abstract::Vagal afferents from the cardiopulmonary region exert a tonic inhibition on the vasomotor center. This is demonstrated by constriction of systemic resistance and splanchnic capacitance vessels and by increased output of renin when the vagi are cut or blocked. In dogs, removal or selective denervation of organs showed ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Thorén PN,Donald DE,Shepherd JT

    更新日期:1976-06-01 00:00:00

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    abstract::Angiotensin II (Ang II) has powerful modulatory actions on cardiovascular function that are mediated by specific receptors located on neurons within the hypothalamus and brain stem. Incubation of neuronal cocultures of rat hypothalamus and brain stem with Ang II elicits an Ang II type 1 (AT1) receptor-mediated inhibit...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Gelband CH,Warth JD,Mason HS,Zhu M,Moore JM,Kenyon JL,Horowitz B,Sumners C

    更新日期:1999-02-19 00:00:00

  • Inhibitor κB kinase 2 is a myosin light chain kinase in vascular smooth muscle.

    abstract:RATIONALE:Myosin light chain (MLC) phosphorylation determines vascular contractile status. In addition to the classic Ca²⁺-dependent MLC kinase (MLCK), another unidentified kinase(s) also contributes to MLC phosphorylation in living cells. Inhibitor κB kinase 2 (IKK2)-deficient mouse embryonic fibroblasts demonstrate a...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ying Z,do Carmo JM,Xiang L,da Silva AA,Chen M,Ryan MJ,Ostrowski M,Rajagopalan S,Hall JE

    更新日期:2013-08-16 00:00:00

  • A TREK-1-like potassium channel in atrial cells inhibited by beta-adrenergic stimulation and activated by volatile anesthetics.

    abstract::Many members of the two-pore-domain potassium (K(+)) channel family have been detected in the mammalian heart but the endogenous correlates of these channels still have to be identified. We investigated whether I(KAA), a background K(+) current activated by negative pressure (stretch) and by arachidonic acid (AA) and ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Terrenoire C,Lauritzen I,Lesage F,Romey G,Lazdunski M

    更新日期:2001-08-17 00:00:00

  • Strongly binding myosin crossbridges regulate loaded shortening and power output in cardiac myocytes.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: McDonald KS,Moss RL

    更新日期:2000-10-27 00:00:00

  • Central command increases muscle sympathetic nerve activity during intense intermittent isometric exercise in humans.

    abstract::During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isome...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Victor RG,Secher NH,Lyson T,Mitchell JH

    更新日期:1995-01-01 00:00:00

  • The effects of human atrial 28-amino acid peptide on systemic and renal hemodynamics in anesthetized rats.

    abstract::The effects of synthetic human atrial 28-amino acid peptide (alpha-human atrial polypeptide) on systemic and renal hemodynamics were examined in two separate groups of Inactin-anesthetized rats. First, mean arterial pressure, heart rate, and cardiac output were measured before and during infusion of the peptide at rat...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hirata Y,Ishii M,Sugimoto T,Matsuoka H,Sugimoto T,Kangawa K,Matsuo H

    更新日期:1985-10-01 00:00:00

  • Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Willis MS,Ike C,Li L,Wang DZ,Glass DJ,Patterson C

    更新日期:2007-03-02 00:00:00