Vascular Permeability

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform

Jeffrey M. Isner - One of the best experts on this subject based on the ideXlab platform.

  • divergence of angiogenic and Vascular Permeability signaling by vegf inhibition of protein kinase c suppresses vegf induced angiogenesis but promotes vegf induced no dependent Vascular Permeability
    Arteriosclerosis Thrombosis and Vascular Biology, 2002
    Co-Authors: Ioakim Spyridopoulos, Toyoaki Murohara, Dongfen Chen, Jeffrey M. Isner, Corinne Luedemann, Donghui Chen, Marianne Kearney, Nicole Principe, Douglas W Losordo
    Abstract:

    Vascular endothelial growth factor (VEGF) promotes angiogenesis by a variety of mechanisms including stimulation of endothelial cell proliferation and migration and increasing Vascular Permeability. Although its mitogenic activity is mediated primarily by the β 2 -isoforms of protein kinase C (PKC), little is known about the signaling pathways transducing its other physiological properties. Accordingly, we used a novel inhibitor molecule to examine the role of PKC isoforms α and β in mediating VEGF-induced angiogenesis and Vascular Permeability. Because conventional inhibitors of PKC, such as staurosporine or calphostin C, also inhibit a variety of other protein kinases, we used a novel compound to specifically inhibit PKC. A myristoylated peptide, which mimics the pseudosubstrate motif of PKC-α and -β subtypes, has been shown to be a highly selective and cell-permeable inhibitor of PKC. Blocking led, as expected, to abrogation of VEGF-induced endothelial cell proliferation in vitro. In vivo, VEGF-induced angiogenesis was impaired by myristoylated peptide. Surprisingly, selective inhibition of PKC induced Vascular Permeability in vivo via a NO-dependent mechanism. Moreover, PKC inhibition led to a 6.4-fold induction of NO synthase (NOS) activity in endothelial cells. Our findings demonstrate that activation of PKC is a major signaling pathway required for VEGF-induced proliferation and angiogenesis, whereas Vascular Permeability was enhanced by blocking PKC. Inhibition of calcium-dependent PKC by itself led to induction of NOS. Although NOS is a downstream target for VEGF-induced angiogenesis, its induction by PKC inhibition was not sufficient to promote neoVascularization. These results reveal that angiogenesis and Vascular Permeability induced by VEGF are mediated by mechanisms which ultimately diverge.

  • Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin
    Circulation, 1998
    Co-Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
    Abstract:

    Background—Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a Vascular Permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microVascular Permeability. The mechanism by which VEGF/VPF increases Vascular Permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced Permeability. Methods and Results—VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased Vascular Permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced Permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase Permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-der...

  • Vascular endothelial growth factor Vascular Permeability factor enhances Vascular Permeability via nitric oxide and prostacyclin
    Circulation, 1998
    Co-Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
    Abstract:

    Background—Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a Vascular Permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microVascular Permeability. The mechanism by which VEGF/VPF increases Vascular Permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced Permeability. Methods and Results—VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased Vascular Permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced Permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase Permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-der...

Toyoaki Murohara - One of the best experts on this subject based on the ideXlab platform.

  • divergence of angiogenic and Vascular Permeability signaling by vegf inhibition of protein kinase c suppresses vegf induced angiogenesis but promotes vegf induced no dependent Vascular Permeability
    Arteriosclerosis Thrombosis and Vascular Biology, 2002
    Co-Authors: Ioakim Spyridopoulos, Toyoaki Murohara, Dongfen Chen, Jeffrey M. Isner, Corinne Luedemann, Donghui Chen, Marianne Kearney, Nicole Principe, Douglas W Losordo
    Abstract:

    Vascular endothelial growth factor (VEGF) promotes angiogenesis by a variety of mechanisms including stimulation of endothelial cell proliferation and migration and increasing Vascular Permeability. Although its mitogenic activity is mediated primarily by the β 2 -isoforms of protein kinase C (PKC), little is known about the signaling pathways transducing its other physiological properties. Accordingly, we used a novel inhibitor molecule to examine the role of PKC isoforms α and β in mediating VEGF-induced angiogenesis and Vascular Permeability. Because conventional inhibitors of PKC, such as staurosporine or calphostin C, also inhibit a variety of other protein kinases, we used a novel compound to specifically inhibit PKC. A myristoylated peptide, which mimics the pseudosubstrate motif of PKC-α and -β subtypes, has been shown to be a highly selective and cell-permeable inhibitor of PKC. Blocking led, as expected, to abrogation of VEGF-induced endothelial cell proliferation in vitro. In vivo, VEGF-induced angiogenesis was impaired by myristoylated peptide. Surprisingly, selective inhibition of PKC induced Vascular Permeability in vivo via a NO-dependent mechanism. Moreover, PKC inhibition led to a 6.4-fold induction of NO synthase (NOS) activity in endothelial cells. Our findings demonstrate that activation of PKC is a major signaling pathway required for VEGF-induced proliferation and angiogenesis, whereas Vascular Permeability was enhanced by blocking PKC. Inhibition of calcium-dependent PKC by itself led to induction of NOS. Although NOS is a downstream target for VEGF-induced angiogenesis, its induction by PKC inhibition was not sufficient to promote neoVascularization. These results reveal that angiogenesis and Vascular Permeability induced by VEGF are mediated by mechanisms which ultimately diverge.

  • Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin
    Circulation, 1998
    Co-Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
    Abstract:

    Background—Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a Vascular Permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microVascular Permeability. The mechanism by which VEGF/VPF increases Vascular Permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced Permeability. Methods and Results—VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased Vascular Permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced Permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase Permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-der...

  • Vascular endothelial growth factor Vascular Permeability factor enhances Vascular Permeability via nitric oxide and prostacyclin
    Circulation, 1998
    Co-Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
    Abstract:

    Background—Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a Vascular Permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microVascular Permeability. The mechanism by which VEGF/VPF increases Vascular Permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced Permeability. Methods and Results—VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased Vascular Permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced Permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase Permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-der...

Dongfen Chen - One of the best experts on this subject based on the ideXlab platform.

  • divergence of angiogenic and Vascular Permeability signaling by vegf inhibition of protein kinase c suppresses vegf induced angiogenesis but promotes vegf induced no dependent Vascular Permeability
    Arteriosclerosis Thrombosis and Vascular Biology, 2002
    Co-Authors: Ioakim Spyridopoulos, Toyoaki Murohara, Dongfen Chen, Jeffrey M. Isner, Corinne Luedemann, Donghui Chen, Marianne Kearney, Nicole Principe, Douglas W Losordo
    Abstract:

    Vascular endothelial growth factor (VEGF) promotes angiogenesis by a variety of mechanisms including stimulation of endothelial cell proliferation and migration and increasing Vascular Permeability. Although its mitogenic activity is mediated primarily by the β 2 -isoforms of protein kinase C (PKC), little is known about the signaling pathways transducing its other physiological properties. Accordingly, we used a novel inhibitor molecule to examine the role of PKC isoforms α and β in mediating VEGF-induced angiogenesis and Vascular Permeability. Because conventional inhibitors of PKC, such as staurosporine or calphostin C, also inhibit a variety of other protein kinases, we used a novel compound to specifically inhibit PKC. A myristoylated peptide, which mimics the pseudosubstrate motif of PKC-α and -β subtypes, has been shown to be a highly selective and cell-permeable inhibitor of PKC. Blocking led, as expected, to abrogation of VEGF-induced endothelial cell proliferation in vitro. In vivo, VEGF-induced angiogenesis was impaired by myristoylated peptide. Surprisingly, selective inhibition of PKC induced Vascular Permeability in vivo via a NO-dependent mechanism. Moreover, PKC inhibition led to a 6.4-fold induction of NO synthase (NOS) activity in endothelial cells. Our findings demonstrate that activation of PKC is a major signaling pathway required for VEGF-induced proliferation and angiogenesis, whereas Vascular Permeability was enhanced by blocking PKC. Inhibition of calcium-dependent PKC by itself led to induction of NOS. Although NOS is a downstream target for VEGF-induced angiogenesis, its induction by PKC inhibition was not sufficient to promote neoVascularization. These results reveal that angiogenesis and Vascular Permeability induced by VEGF are mediated by mechanisms which ultimately diverge.

  • Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin
    Circulation, 1998
    Co-Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
    Abstract:

    Background—Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a Vascular Permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microVascular Permeability. The mechanism by which VEGF/VPF increases Vascular Permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced Permeability. Methods and Results—VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased Vascular Permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced Permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase Permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-der...

  • Vascular endothelial growth factor Vascular Permeability factor enhances Vascular Permeability via nitric oxide and prostacyclin
    Circulation, 1998
    Co-Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
    Abstract:

    Background—Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a Vascular Permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microVascular Permeability. The mechanism by which VEGF/VPF increases Vascular Permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced Permeability. Methods and Results—VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased Vascular Permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced Permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase Permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-der...

Sara M. Weis - One of the best experts on this subject based on the ideXlab platform.

  • Vascular Permeability in cardioVascular disease and cancer.
    Current opinion in hematology, 2008
    Co-Authors: Sara M. Weis
    Abstract:

    Purpose of reviewRegulation of endothelial barrier function is critical for Vascular homeostasis, as dynamic and local control of Vascular Permeability permits macromolecular transport, immune surveillance, and deposition of a fibrin barrier to contain infection at sites of inflammation. Many of the

  • Pathophysiological consequences of VEGF-induced Vascular Permeability
    Nature, 2005
    Co-Authors: Sara M. Weis, David A. Cheresh
    Abstract:

    Although Vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts Vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes Vascular Permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the Vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the Vascular Permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.

Ronald G. Pearl - One of the best experts on this subject based on the ideXlab platform.

  • Nitroglycerin does not alter pulmonary Vascular Permeability in isolated rabbit lungs.
    Anesthesia and analgesia, 1997
    Co-Authors: J. S. Thompson, Brian P. Kavanagh, Ronald G. Pearl
    Abstract:

    Nitroglycerin (NTG) produces vasodilation by releasing nitric oxide (NO) at the cellular level. Other studies have suggested that NO may directly alter Vascular Permeability and may alter the development of tissue injury. We therefore examined the effects of NTG on Vascular Permeability in the buffer-perfused rabbit lung under normal conditions and during lung injury. Vascular Permeability was assessed by measurement of the capillary filtration coefficient (Kf,c). In normal lungs, NTG did not alter Kf,c or the rate of weight gain. Oxidant lung injury was produced by the addition of purine and xanthine oxidase and resulted in increased Kf,c and increased weight gain. However, NTG did not alter these effects of oxidant lung injury. We conclude that NTG does not alter pulmonary Vascular Permeability in either normal or oxidant-injured lungs.