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Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor
W.G. Roberts, G.E. Palade
Journal of Cell Science 1995 108: 2369-2379;

Summary

The vascular endothelial growth factor (VEGF) was originally described as vascular permeability factor due to its ability to increase microvascular permeability to plasma proteins. However, the vessel types (arteriolar, venular, and capillary) affected by VEGF and the modification of endothelial morphology in response to increased permeability induced by VEGF in vivo have not been precisely documented. By topical application or intradermal injection of recombinant human VEGF-165 we find that VEGF increases the permeability of postcapillary venules as well as muscular venules and capillaries. Surprisingly, we also find that endothelia of small venules and capillaries become fenestrated within 10 minutes of VEGF application. Fenestrations appeared in vascular beds which do not normally have fenestrated endothelium, namely the cremaster muscle and skin. Histamine, saline, and heat-inactivated VEGF do not cause fenestrations. Increased permeability is completely inhibited when VEGF is cleared by immunoprecipitation with anti-VEGF monoclonal antibodies. The VEGF effect on permeability is unlike that of any other mediator described to date since both muscular venules and capillaries are affected.

REFERENCES

    1. Abell R. G.
    (1946). Permeability of blood capillary sprouts and newly formed blood capillaries as compared to that of older blood capillaries. Am. J. Physiol 147, 237–241
    OpenUrlFREE Full Text
    1. Adamis A. P.,
    2. Shima D. T.,
    3. Yeo K.-T. and
    4. et al.
    (1993). Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem. Biophys. Res. Commun 193, 631–638
    OpenUrlCrossRefPubMedWeb of Science
    1. Aiello L. P.,
    2. Avery R. L.,
    3. Arrigg P. G. and
    4. et al.
    (1994). Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. New Engl. J. Med 331, 1480–1519
    OpenUrlCrossRefPubMedWeb of Science
    1. Albelda S. M.,
    2. Muller W. A.,
    3. Buck C. A. and
    4. Newman P. J.
    (1991). Molecular and cellular properties of PECAM-1 (endoCAM/CD31): A novel vascular cell-cell adhesion molecule. J. Cell Biol 114, 1059–1068
    OpenUrlAbstract/FREE Full Text
    1. Bearer E. L. and
    2. Orci L.
    (1985). Endothelial fenestral diaphragms: A quick-freeze, deep-etch study. J. Cell Biol 100, 418–428
    OpenUrlAbstract/FREE Full Text
    1. Berkman R. A.,
    2. Merrill M. J.,
    3. Reinhold W. C. and
    4. et al.
    (1993). Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J. Clin. Invest 91, 153–159
    OpenUrlCrossRefPubMedWeb of Science
    1. Bonafanti R.,
    2. Furie B. C.,
    3. Furie B. and
    4. Wagner D. D.
    (1989). PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood 73, 1109–1112
    OpenUrlAbstract/FREE Full Text
    1. Braverman I. M. and
    2. Yen A.
    (1977). Ultrastructure of the capillary loops in the dermal papillae of psoriasis. J. Invest. Derm 68, 53–60
    OpenUrlCrossRefPubMedWeb of Science
    1. Breier G.,
    2. Albrecht U.,
    3. Sterrer S. and
    4. Risau W.
    (1992). Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114, 521–532
    OpenUrlAbstract
    1. Brock T. A.,
    2. Dvorak H. F. and
    3. Senger D. R.
    (1991). Tumor-secreted vascular permeability factor increases cytosolic Ca++and von Willebrand factor release in human endothelial cells. Am. J. Path 138, 213–221
    OpenUrlPubMedWeb of Science
    1. Brown L. F.,
    2. Berse B.,
    3. Tognazzi K. and
    4. et al.
    (1992). Vascular permeability factor mRNA and protein expression in human kidney. Kidney Int 42, 1457–1461
    OpenUrlCrossRefPubMedWeb of Science
    1. Brown L. F.,
    2. Yeo K.-T.,
    3. Berse B. and
    4. et al.
    (1992). Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J. Exp. Med 176, 1375–1379
    OpenUrlAbstract/FREE Full Text
    1. Burns M. S. and
    2. Hartz M. J.
    (1992). The retinal pigment epithelium induces fenestration of endothelial cells in vivo. Curr. Eye Res 11, 863–873
    OpenUrlCrossRefPubMedWeb of Science
    1. Clauss M.,
    2. Gerlach M.,
    3. Gerlach H. and
    4. et al.
    (1990). Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J. Exp. Med 172, 1535–1545
    OpenUrlAbstract/FREE Full Text
    1. Clementi F. and
    2. Palade G. E.
    (1969). Intestinal capillaries. I. Permeability to peroxidase and ferritin. J. Cell Biol 41, 33–58
    OpenUrlAbstract/FREE Full Text
    1. De Almeida O. P. and
    2. Bohm G. M.
    (1978). Vascular permeability in the rat gingiva. A model of vessel response in chronic inflammation. Am. J. Path 127, 27–34
    OpenUrl
    1. De Vries C.,
    2. Escobedo J. A.,
    3. Ueno H.,
    4. Houck K.,
    5. Ferrara N. and
    6. Williams L. T.
    (1992). The fms -like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255, 989–991
    OpenUrlAbstract/FREE Full Text
    1. Detmar M.,
    2. Brown L. F.,
    3. Claffey K. P. and
    4. et al.
    (1994). Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J. Exp. Med 180, 1141–1146
    OpenUrlAbstract/FREE Full Text
    1. Farquhar M. G.
    (1961). Fine structure and function in capillaries of the anterior pituitary gland. Angiology 12, 270–292
    OpenUrlCrossRefPubMedWeb of Science
    1. Ferrara N. and
    2. Henzel W. J.
    (1989). Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem. Biophys. Res. Commun 161, 851–858
    OpenUrlCrossRefPubMedWeb of Science
    1. Ferrara N.,
    2. Leung D. W.,
    3. Cachianes G.,
    4. Winer J. and
    5. Henzel W. J.
    (1991). Purification and cloning of vascular endothelial growth factor secreted by pituitary folliculostellate cells. Meth. Enzymol 198, 391–405
    OpenUrlPubMedWeb of Science
    1. Ferrara N.,
    2. Houck K.,
    3. Jakeman L. and
    4. Leung D. W.
    (1992). Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endo. Rev. 13, 18–32
    OpenUrl
    1. Ferrara N.,
    2. Winer J.,
    3. Burton T. and
    4. et al.
    (1993). Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to chinese hamster ovary cells. J. Clin. Invest 91, 160–170
    OpenUrlCrossRefPubMedWeb of Science
    1. Gitay-Goren H.,
    2. Soker S.,
    3. Vlodavsky I. and
    4. Neufeld G.
    (1992). The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. J. Biol. Chem 267, 6093–6098
    OpenUrlAbstract/FREE Full Text
    1. Granger D. N.,
    2. Granger J. P.,
    3. Brace R. A.,
    4. Parker R. E. and
    5. Taylor A. E.
    (1979). Analysis of the permeability characteristics of cat intestinal capillaries. Circ. Res 44, 335–344
    OpenUrlFREE Full Text
    1. Hayes B. K.,
    2. Freeze H. H. and
    3. Varki A.
    (1993). Biosynthesis of oligosaccharides in intact Golgi preparations from rat liver. Analysis of N-linked glycans labeled by UDP-[6-3H]N-acetylglucosamine. J. Biol. Chem 268, 16139–16154
    OpenUrlAbstract/FREE Full Text
    1. Jakeman L. B.,
    2. Winer J.,
    3. Bennett G. L.,
    4. Altar C. A. and
    5. Ferrara N.
    (1992). Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J. Clin. Invest 89, 244–253
    OpenUrlCrossRefPubMedWeb of Science
    1. Joris I.,
    2. Cuenoud H. F.,
    3. Doern G. V.,
    4. Underwood J. M. and
    5. Majno G.
    (1990). Capillary leakage in inflammation. Am. J. Path 137, 1353–1363
    OpenUrlPubMedWeb of Science
    1. Koch A. E.,
    2. Harlow L. A.,
    3. Haines G. K. and
    4. et al.
    (1994). Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J. Immunol 152, 4149–4156
    OpenUrlAbstract
    1. Kohn S.,
    2. Nagy J. A.,
    3. Dvorak H. F. and
    4. Dvorak A. M.
    (1992). Pathways of macromolecular tracer transport across venules and small veins. Lab. Invest 67, 596–607
    OpenUrlPubMedWeb of Science
    1. Leung D. W.,
    2. Cachienes G.,
    3. Kuang W.-J.,
    4. Goeddel D. V. and
    5. Ferrara N.
    (1989). Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246, 1306–1309
    OpenUrlAbstract/FREE Full Text
    1. McEver R. P.,
    2. Beckstead J. H.,
    3. Moore K. L.,
    4. Marshall-Carlsen L. and
    5. Bainton D. F.
    (1989). GMP-140, a plateletgranule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J. Clin. Invest 84, 92–99
    OpenUrlCrossRefPubMedWeb of Science
    1. McKinney R. V.,
    2. Singh B. B. and
    3. Brewer P. D.
    (1977). Fenestrations in regenerating skeletal muscle capillaries. Am. J. Anat 150, 213–218
    OpenUrlCrossRefPubMedWeb of Science
    1. Miles A. A. and
    2. Miles E. M.
    (1952). Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs. J. Physiol 118, 228–257
    OpenUrlCrossRefPubMedWeb of Science
    1. Millauer B.,
    2. Wizigmann-Voos S.,
    3. Schnurch H. and
    4. et al.
    (1993). High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835–846
    OpenUrlCrossRefPubMedWeb of Science
    1. Miller J. W.,
    2. Adamis A. P.,
    3. Shima D. T. and
    4. et al.
    (1994). Vascular endothelial growth factor/Vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am. J. Path 145, 574–584
    OpenUrlPubMedWeb of Science
    1. Monacci W. T.,
    2. Merrill M. J. and
    3. Oldfield E. H.
    (1993). Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am. J. Physiol 264, 995–.
    OpenUrl
    1. Muller W. A.,
    2. Ratti C. M.,
    3. McDonnell S. L. and
    4. Cohn Z. A.
    (1989). A human endothelial cell-restricted externally disposed plasmalemmal protein enriched in intercellular junctions. J. Exp. Med 170, 399–414
    OpenUrlAbstract/FREE Full Text
    1. Peters K. G.,
    2. De Vries C. and
    3. Williams L. T.
    (1993). Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. Proc. Nat. Acad. Sci 90, 8915–8919
    OpenUrlAbstract/FREE Full Text
    1. Plate K. H.,
    2. Breier G.,
    3. Weich H. A. and
    4. Risau W.
    (1992). Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359, 845–848
    OpenUrlCrossRefPubMedWeb of Science
    1. Plate K. H.,
    2. Breier G.,
    3. Millauer B.,
    4. Ullrich A. and
    5. Risau W.
    (1993). Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 53, 5822–5827
    OpenUrlAbstract/FREE Full Text
    1. Quinn T. P.,
    2. Peters K. G.,
    3. DeVries C.,
    4. Ferrara N. and
    5. Williams L. T.
    (1993). Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc. Nat. Acad. Sci 90, 7533–7537
    OpenUrlAbstract/FREE Full Text
    1. Roberts W. G. and
    2. Hasan T.
    (1993). Tumor-secreted vascular endothelial growth factor/vascular permeability factor influences photosensitizer uptake. Cancer Res 53, 153–157
    OpenUrlAbstract/FREE Full Text
    1. Schimmenti L. A.,
    2. Yan H.-C.,
    3. Madri J. A. and
    4. Albelda S. M.
    (1992). Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration. J. Cell. Phys 153, 417–428
    OpenUrlCrossRefPubMedWeb of Science
    1. Schoefl G. I.
    (1963). Studies on inflammation III. Growing capillaries: Their structure and permeability. Virchows Arch. path. Anat 337, 97–141
    OpenUrlCrossRef
    1. Senger D. R.,
    2. Galli S. J.,
    3. Dvorak A. M.,
    4. Perruzzi C. A.,
    5. Harvey V. S. and
    6. Dvorak H. F.
    (1983). Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219, 983–985
    OpenUrlAbstract/FREE Full Text
    1. Senger D. R.,
    2. Connolly D. T.,
    3. Van De Water L.,
    4. Feder J. and
    5. Dvorak H. F.
    (1990). Purification and NH2-terminal amino acid sequence of guinea pig tumor secreted vascular permeability factor. Cancer Res 50, 1774–1778
    OpenUrlAbstract/FREE Full Text
    1. Senger D. R.,
    2. Van De Water L.,
    3. Brown L. F. and
    4. et al.
    (1993). Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metast. Rev. 12, 303–324
    OpenUrlCrossRefPubMedWeb of Science
    1. Simionescu M.,
    2. Simionescu N.,
    3. Silbert J. E. and
    4. Palade G. E.
    (1981). Differentiated microdomains on the luminal surface of the capillary endothelium II. Partial characterization of their anionic sites. J. Cell Biol 90, 614–621
    OpenUrlAbstract/FREE Full Text
    1. Simionescu N.,
    2. Siomionescu M. and
    3. Palade G. E.
    (1981). Differentiated microdomains on the luminal surface of the capillary endothelium I. Preferential distribution of anionic sites. J. Cell Biol 90, 605–613
    OpenUrlAbstract/FREE Full Text
    1. Tischer E.,
    2. Mitchell R.,
    3. Hartman T. and
    4. et al.
    (1991). The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J. Biol. Chem 266, 11947–11954
    OpenUrlAbstract/FREE Full Text
    1. Yamaguchi T. P.,
    2. Dumont D. J.,
    3. Conlon R. A.,
    4. Breitman M. L. and
    5. Rossant J.
    (1993). flk-1, an flt- related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118, 489–498
    OpenUrlAbstract
    1. Yeo K.-T.,
    2. Wang H. H.,
    3. Nagy J. A. and
    4. et al.
    (1993). Vascular permeability factor (Vascular endothelial growth factor) in guinea pig and human tumor and inflammatory effusions. Cancer Res 53, 2912–2918
    OpenUrlAbstract/FREE Full Text
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Journal Articles
Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor
W.G. Roberts, G.E. Palade
Journal of Cell Science 1995 108: 2369-2379;
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