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The Role of VEGF in Controlling Vascular Permeability

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Tumor Angiogenesis

Abstract

Blood vessels in different organs have vastly different morphologies and functions. One important aspect of vessel heterogeneity is its exchange with the surrounding tissue. While vessels in the CNS are highly restricted in their exchange, vessels in peripheral organs may be quite permeable and allow solvent and small molecules to pass across the vessel wall. A more extensive permeability, or leakage, can be induced in an acute, transient manner by specific factors, with the purpose to deliver blood constituents to the interstitial space. The interstitial fluid is drained by the lymphatic vasculature and eventually delivered back to the blood circulation via the subclavian veins. Larger volumes of accumulated interstitial fluid, edema, are a sign of extensive leakage and/or poor uptake of fluid by the lymphatics. Through the continuous blood and lymphatic circulation, the maintenance of tissue homeostasis is ensured through the delivery of oxygen and nutrients to the tissues. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and leaky vessels with poor blood flow and tissue swelling potentially exacerbated by poorly functioning lymphatics. Elevated interstitial pressure, hypoxia, and a chaotic tissue microenvironment promote the disease. This review is focused on the role of vascular endothelial growth factors (VEGFs) and their receptors in the control of vessel integrity.

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References

  • Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478

    Article  CAS  PubMed  Google Scholar 

  • Adamson RH, Zeng M, Adamson GN, Lenz JF, Curry FE (2003) PAF- and bradykinin-induced hyperpermeability of rat venules is independent of actin-myosin contraction. Am J Physiol Heart Circ Physiol 285:H406–H417

    Article  CAS  PubMed  Google Scholar 

  • Adkins JN, Varnum SM, Auberry KJ, Moore RJ, Angell NH, Smith RD, Springer DL, Pounds JG (2002) Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry. Mol Cell Proteomics 1:947–955

    Article  CAS  PubMed  Google Scholar 

  • Antonetti DA, Lieth E, Barber AJ, Gardner TW (1999) Molecular mechanisms of vascular permeability in diabetic retinopathy. Semin Ophthalmol 14:240–248

    Article  CAS  PubMed  Google Scholar 

  • Argaw AT, Gurfein BT, Zhang Y, Zameer A, John GR (2009) VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci USA 106:1977–1982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561

    Article  CAS  PubMed  Google Scholar 

  • Augustin HG, Koh GY (2017) Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science 357(6353):eaal2379. https://doi.org/10.1126/science.aal2379

    Article  CAS  PubMed  Google Scholar 

  • Azzi S, Hebda JK, Gavard J (2013) Vascular permeability and drug delivery in cancers. Front Oncol 3:211

    Article  PubMed  PubMed Central  Google Scholar 

  • Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Munzel T, Simoons ML, Hamm CW (2003) Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 108:1440–1445

    Article  CAS  PubMed  Google Scholar 

  • Baluk P, Hirata A, Thurston G, Fujiwara T, Neal CR, Michel CC, McDonald DM (1997) Endothelial gaps: time course of formation and closure in inflamed venules of rats. Am J Phys 272:L155–L170

    CAS  Google Scholar 

  • Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, Vestweber D, Corada M, Molendini C, Dejana E, McDonald DM (2007) Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 204:2349–2362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barar J, Asadi M, Mortazavi-Tabatabaei SA, Omidi Y (2009) Ocular drug delivery; impact of in vitro cell culture models. J Ophthalmic Vis Res 4:238–252

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baskurt OK, Yalcin O, Meiselman HJ (2004) Hemorheology and vascular control mechanisms. Clin Hemorheol Microcirc 30:169–178

    PubMed  Google Scholar 

  • Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology 7:452–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braet F, De Zanger R, Baekeland M, CrabbÉ E, Van Der Smissen P, Wisse E (1995) Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells. Hepatology 21:180–189

    CAS  PubMed  Google Scholar 

  • Brieher WM, Yap AS (2013) Cadherin junctions and their cytoskeleton(s). Curr Opin Cell Biol 25:39–46

    Article  CAS  PubMed  Google Scholar 

  • Brindle NP, Saharinen P, Alitalo K (2006) Signaling and functions of angiopoietin-1 in vascular protection. Circ Res 98:1014–1023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown EB, Campbell RB, Tsuzuki Y, Xu L, Carmeliet P, Fukumura DAI, Jain RK (2001) In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy. Nat Med 7:864–868

    Article  CAS  PubMed  Google Scholar 

  • Carbone F, Nencioni A, Mach F, Vuilleumier N, Montecucco F (2013) Pathophysiological role of neutrophils in acute myocardial infarction. Thromb Haemost 110:501–514

    Article  CAS  PubMed  Google Scholar 

  • Cavusoglu E, Ruwende C, Eng C, Chopra V, Yanamadala S, Clark LT, Pinsky DJ, Marmur JD (2007) Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome. Am J Cardiol 99:1364–1368

    Article  CAS  PubMed  Google Scholar 

  • Chang SH, Feng D, Nagy JA, Sciuto TE, Dvorak AM, Dvorak HF (2009) Vascular permeability and pathological angiogenesis in caveolin-1-null mice. Am J Pathol 175:1768–1776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cueni LN, Detmar M (2008) The lymphatic system in health and disease. Lymphat Res Biol 6:109–122

    Article  PubMed  Google Scholar 

  • Curry FR (2005) Microvascular solute and water transport. Microcirculation 12:17–31

    Article  CAS  PubMed  Google Scholar 

  • Dejana E, Bazzoni G, Lampugnani MG (1999) Vascular endothelial (VE)-cadherin: only an intercellular glue? Exp Cell Res 252:13–19

    Article  CAS  PubMed  Google Scholar 

  • Dejana E, Spagnuolo R, Bazzoni G (2001) Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration. Thromb Haemost 86:308–315

    Article  CAS  PubMed  Google Scholar 

  • Dejana E, Orsenigo F, Lampugnani MG (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 121:2115–2122

    Article  CAS  PubMed  Google Scholar 

  • Di Lorenzo A, Fernandez-Hernando C, Cirino G, Sessa WC (2009) Akt1 is critical for acute inflammation and histamine-mediated vascular leakage. Proc Natl Acad Sci USA 106:14552–14557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605

    Article  CAS  PubMed  Google Scholar 

  • Dvorak HF (2010) Vascular permeability to plasma, plasma proteins, and cells: an update. Curr Opin Hematol 17:225–229

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dvorak AM, Feng D (2001) The vesiculo-vacuolar organelle (VVO). A new endothelial cell permeability organelle. J Histochem Cytochem 49:419–432

    Article  CAS  PubMed  Google Scholar 

  • Dvorak HF, Harvey VS, Estrella P, Brown LF, Mcdonagh J, Dvorak AM (1987) Fibrin containing gels induce angiogenesis. Implications for tumor stroma generation and wound healing. Lab Invest 57:673–686

    CAS  PubMed  Google Scholar 

  • Egawa G, Nakamizo S, Natsuaki Y, Doi H, Miyachi Y, Kabashima K (2013) Intravital analysis of vascular permeability in mice using two-photon microscopy. Sci Rep 3:1932

    Article  PubMed  PubMed Central  Google Scholar 

  • Eliceiri BP, Paul R, Schwartzberg PL, Hood JD, Leng J, Cheresh DA (1999) Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell 4:915–924

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N (2005) VEGF as a therapeutic target in cancer. Oncology 69(Suppl 3):11–16

    Article  CAS  PubMed  Google Scholar 

  • Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837 837a-837d

    Article  CAS  PubMed  Google Scholar 

  • Fukuhra S, Sakurai A, Yamagishi A, Sako K, Mochizuki N (2006) Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small GTPase, Rap1. J Biochem Mol Biol 39:132–139

    CAS  PubMed  Google Scholar 

  • Fukumura D, Gohongi T, Kadambi A, Izumi Y, Ang J, Yun CO, Buerk DG, Huang PL, Jain RK (2001) Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Proc Natl Acad Sci U S A 98:2604–2609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukumura DAI, Duda DG, Munn LL, Jain RK (2010) Tumor microvasculature and microenvironment: novel insights through Intravital imaging in pre-clinical models. Microcirculation 17:206–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase AKT. Nature 399:597–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Funa NS, Kriz V, Zang G, Calounova G, Akerblom B, Mares J, Larsson E, Sun Y, Betsholtz C, Welsh M (2009) Dysfunctional microvasculature as a consequence of shb gene inactivation causes impaired tumor growth. Cancer Res 69:2141–2148

    Article  CAS  PubMed  Google Scholar 

  • Gardner TW, Antonetti DA, Barber AJ, Lieth E, Tarbell JA (1999) The molecular structure and function of the inner blood-retinal barrier. Penn State Retina Research Group. Doc Ophthalmol 97:229–237

    Article  CAS  PubMed  Google Scholar 

  • Gavard J, Gutkind JS (2006) VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol 8:1223–1234

    Article  CAS  PubMed  Google Scholar 

  • Hudson N, Powner MB, Sarker MH, Burgoyne T, Campbell M, Ockrim ZK, Martinelli R, Futter CE, Grant MB, Fraser PA, Shima DT, Greenwood J, Turowski P (2014) Differential apicobasal VEGF signaling at vascular blood-neural barriers. Dev Cell 30:541–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    Article  CAS  PubMed  Google Scholar 

  • Jain RK, Tong RT, Munn LL (2007) Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model. Cancer Res 67:2729–2735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jalali S, Li YS, Sotoudeh M, Yuan S, Li S, Chien S, Shyy JY (1998) Shear stress activates p60src-Ras-MAPK signaling pathways in vascular endothelial cells. Arterioscler Thromb Vasc Biol 18:227–234

    Article  CAS  PubMed  Google Scholar 

  • Jennings D, Raghunand N, Gillies RJ (2008) Imaging hemodynamics. Cancer Metastasis Rev 27:589–613

    Article  PubMed  PubMed Central  Google Scholar 

  • Jin ZG, Ueba H, Tanimoto T, Lungu AO, Frame MD, Berk BC (2003) Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circ Res 93:354–363

    Article  CAS  PubMed  Google Scholar 

  • Karakas M, Koenig W, Zierer A, Herder C, Rottbauer W, Baumert J, Meisinger C, Thorand B (2012) Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study. J Intern Med 271:43–50

    Article  CAS  PubMed  Google Scholar 

  • Kim M, Allen B, Korhonen EA, Nitschke M, Yang HW, Baluk P, Saharinen P, Alitalo K, Daly C, THURSTON G, McDonald DM (2016) Opposing actions of angiopoietin-2 on Tie2 signaling and Foxo1 activation. J Clin Invest 126:3511–3525

    Article  PubMed  PubMed Central  Google Scholar 

  • Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L (2011) Signal transduction by vascular endothelial growth factor receptors. Biochem J 437:169–183

    Article  CAS  PubMed  Google Scholar 

  • Kohn S, Nagy JA, Dvorak HF, Dvorak AM (1992) Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels. Lab Invest 67:596–607

    CAS  PubMed  Google Scholar 

  • Korhonen EA, Lampinen A, Giri H, Anisimov A, Kim M, Allen B, Fang S, D'amico G, Sipila TJ, Lohela M, Strandin T, Vaheri A, Yla-Herttuala S, Koh GY, McDonald DM, Alitalo K, Saharinen P (2016) Tie1 controls angiopoietin function in vascular remodeling and inflammation. J Clin Invest 126:3495–3510

    Article  PubMed  PubMed Central  Google Scholar 

  • Korn C, Augustin HG (2015) Mechanisms of vessel pruning and regression. Dev Cell 34:5–17

    Article  CAS  PubMed  Google Scholar 

  • Kourtidis A, Ngok SP, Anastasiadis PZ (2013) p120 catenin: an essential regulator of cadherin stability, adhesion-induced signaling, and cancer progression. Prog Mol Biol Transl Sci 116:409–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E (2006) Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol 174:593–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanitis E, Irving M, Coukos G (2015) Targeting the tumor vasculature to enhance T cell activity. Curr Opin Immunol 33:55–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leak LV, Burke JF (1966) Fine structure of the lymphatic capillary and the adjoining connective tissue area. Am J Anat 118:785–809

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela-Arispe ML (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130:691–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Padhan N, Sjostrom EO, Roche FP, Testini C, Honkura N, Sainz-Jaspeado M, Gordon E, Bentley K, Philippides A, Tolmachev V, Dejana E, Stan RV, Vestweber D, Ballmer-Hofer K, Betsholtz C, Pietras K, Jansson L, Claesson-Welsh L (2016) VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread. Nat Commun 7:11017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liao D, Johnson RS (2007) Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev 26:281–290

    Article  CAS  PubMed  Google Scholar 

  • Ma YP, Koo A, Kwan HC, Cheng KK (1974) On-line measurement of the dynamic velocity of erythrocytes in the cerebral microvessels in the rat. Microvasc Res 8:1–13

    Article  CAS  PubMed  Google Scholar 

  • Majno G, Shea SM, Leventhal M (1969) Endothelial contraction induced by histamine-type mediators: an electron microscopic study. J Cell Biol 42:647–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall I (1984) Characterization and distribution of histamine H1- and H2-receptors in precapillary vessels. J Cardiovasc Pharmacol 6(Suppl 4):S587–S597

    Article  PubMed  Google Scholar 

  • Matsumoto T, Bohman S, Dixelius J, Berge T, Dimberg A, Magnusson P, Wang L, Wikner C, Qi JH, Wernstedt C, Wu J, Bruheim S, Mugishima H, Mukhopadhyay D, Spurkland A, Claesson-Welsh L (2005) VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. EMBO J 24:2342–2353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDonald DM, Baluk P (2005) Imaging of angiogenesis in inflamed airways and tumors: newly formed blood vessels are not alike and may be wildly abnormal: Parker B Francis lecture. Chest 128:602S–608S

    Article  PubMed  Google Scholar 

  • Meininger GA, Davis MJ (1992) Cellular mechanisms involved in the vascular myogenic response. Am J Phys 263:H647–H659

    CAS  Google Scholar 

  • Meuwese MC, Stroes ES, Hazen SL, Van Miert JN, Kuivenhoven JA, Schaub RG, Wareham NJ, Luben R, Kastelein JJ, Khaw KT, Boekholdt SM (2007) Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol 50:159–165

    Article  CAS  PubMed  Google Scholar 

  • Miller JW, Le Couter J, Strauss EC, Ferrara N (2013) Vascular endothelial growth factor a in intraocular vascular disease. Ophthalmology 120:106–114

    Article  PubMed  Google Scholar 

  • Nagy JA, Benjamin L, Zeng H, Dvorak AM, Dvorak HF (2008) Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 11:109–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nourshargh S, Hordijk PL, Sixt M (2010) Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol 11:366–378

    Article  CAS  PubMed  Google Scholar 

  • Orsenigo F, Giampietro C, Ferrari A, Corada M, Galaup A, Sigismund S, Ristagno G, Maddaluno L, Koh GY, Franco D, Kurtcuoglu V, Poulikakos D, Baluk P, McDonald D, Grazia Lampugnani M, Dejana E (2012) Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo. Nat Commun 3:1208

    Article  PubMed  CAS  Google Scholar 

  • Paolinelli R, Corada M, Orsenigo F, Dejana E (2011) The molecular basis of the blood brain barrier differentiation and maintenance. Is it still a mystery? Pharmacol Res 63:165–171

    Article  CAS  PubMed  Google Scholar 

  • Phillipson M, Kubes P (2011) The neutrophil in vascular inflammation. Nat Med 17:1381–1390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phung TL, Ziv K, Dabydeen D, Eyiah-Mensah G, Riveros M, Perruzzi C, Sun J, Monahan-Earley RA, Shiojima I, Nagy JA, Lin MI, Walsh K, Dvorak AM, Briscoe DM, Neeman M, Sessa WC, Dvorak HF, Benjamin LE (2006) Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell 10:159–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pink DBS, Schulte W, Parseghian MH, Zijlstra A, Lewis JD (2012) Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery. PLoS One 7:e33760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Potente M, Makinen T (2017) Vascular heterogeneity and specialization in development and disease. Nat Rev Mol Cell Biol 18:477–494

    Article  CAS  PubMed  Google Scholar 

  • Proulx ST, Luciani P, Christiansen A, Karaman S, Blum KS, Rinderknecht M, Leroux JC, Detmar M (2013) Use of a PEG-conjugated bright near-infrared dye for functional imaging of rerouting of tumor lymphatic drainage after sentinel lymph node metastasis. Biomaterials 34:5128–5137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reitsma S, Slaaf DW, Vink H, Van Zandvoort MA, Oude Egbrink MG (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454:345–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108(Pt 6):2369–2379

    CAS  PubMed  Google Scholar 

  • Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K (2008) Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol 10:527–537

    Article  CAS  PubMed  Google Scholar 

  • Sakai T, Hosoyamada Y (2013) Are the precapillary sphincters and metarterioles universal components of the microcirculation? An historical review. J Physiol Sci 63:319–331

    Article  PubMed  PubMed Central  Google Scholar 

  • Sakurai Y, Ohgimoto K, Kataoka Y, Yoshida N, Shibuya M (2005) Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci USA 102:1076–1081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulte D, Kuppers V, Dartsch N, Broermann A, Li H, Zarbock A, Kamenyeva O, Kiefer F, Khandoga A, Massberg S, Vestweber D (2011) Stabilizing the VE-cadherin-catenin complex blocks leukocyte extravasation and vascular permeability. EMBO J 30:4157–4170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985

    Article  CAS  PubMed  Google Scholar 

  • Sharma JN, Al-Dhalmawi GS (2003) Bradykinin receptor antagonists: therapeutic implications. IDrugs 6:581–586

    CAS  PubMed  Google Scholar 

  • Shibuya M (2011) Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-Angiogenic therapies. Genes Cancer 2:1097–1105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Simons M, Gordon E, Claesson-Welsh L (2016) Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol 17:611–625

    Article  CAS  PubMed  Google Scholar 

  • Singh M, Ferrara N (2012) Modeling and predicting clinical efficacy for drugs targeting the tumor milieu. Nat Biotechnol 30:648–657

    Article  CAS  PubMed  Google Scholar 

  • Soltani M, Chen P (2013) Numerical modeling of interstitial fluid flow coupled with blood flow through a remodeled solid tumor microvascular network. PLoS One 8:e67025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG (2014) Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer 14:159–172

    Article  CAS  PubMed  Google Scholar 

  • Stalmans I, Ng YS, Rohan R, Fruttiger M, Bouche A, Yuce A, Fujisawa H, Hermans B, Shani M, Jansen S, Hicklin D, Anderson DJ, Gardiner T, Hammes HP, Moons L, Dewerchin M, Collen D, Carmeliet P, D'amore PA (2002) Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 109:327–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stan RV, Tse D, Deharvengt SJ, Smits NC, Xu Y, Luciano MR, Mcgarry CL, Buitendijk M, Nemani KV, Elgueta R, Kobayashi T, Shipman SL, Moodie KL, Daghlian CP, Ernst PA, Lee HK, Suriawinata AA, Schned AR, Longnecker DS, Fiering SN, Noelle RJ, Gimi B, Shworak NW, Carriere C (2012) The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition. Dev Cell 23:1203–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stapleton S, Milosevic M, Allen C, Zheng J, Dunne M, Yeung I, Jaffray DA (2013) A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors. PLoS One 8:e81157

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stewart MW (2012) The expanding role of vascular endothelial growth factor inhibitors in ophthalmology. Mayo Clin Proc 87:77–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (2013) Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm 10:1473–1491

    Article  CAS  PubMed  Google Scholar 

  • Sun Z, Li X, Massena S, Kutschera S, Padhan N, Gualandi L, Sundvold-Gjerstad V, Gustafsson K, Choy WW, Zang G, Quach M, Jansson L, Phillipson M, Abid MR, Spurkland A, Claesson-Welsh L (2012) VeGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd. J Exp Med 209:1363–1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thibeault S, Rautureau Y, Oubaha M, Faubert D, Wilkes BC, Delisle C, Gratton JP (2010) S-nitrosylation of beta-catenin by eNOS-derived NO promotes VEGF-induced endothelial cell permeability. Mol Cell 39:468–476

    Article  CAS  PubMed  Google Scholar 

  • Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM (1999) Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286:2511–2514

    Article  CAS  PubMed  Google Scholar 

  • Tornavaca O, Chia M, Dufton N, Almagro LO, Conway DE, Randi AM, Schwartz MA, Matter K, Balda MS (2015) Zo-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. J Cell Biol 208:821–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tse D, Stan RV (2010) Morphological heterogeneity of endothelium. Semin Thromb Hemost 36:236–245

    Article  CAS  PubMed  Google Scholar 

  • Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, Delisser H, Schwartz MA (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–431

    Article  CAS  PubMed  Google Scholar 

  • Vaahtomeri K, Karaman S, Makinen T, Alitalo K (2017) Lymphangiogenesis guidance by paracrine and pericellular factors. Genes Dev 31:1615–1634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valenta T, Hausmann G, Basler K (2012) The many faces and functions of beta-catenin. EMBO J 31:2714–2736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vempati P, Popel AS, Mac Gabhann F (2014) Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning. Cytokine Growth Factor Rev 25:1–19

    Article  CAS  PubMed  Google Scholar 

  • Venkatraman L, Tucker-Kellogg L (2013) The CD47-binding peptide of thrombospondin-1 induces defenestration of liver sinusoidal endothelial cells. Liver Int 33:1386–1397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vestweber D (2012) Relevance of endothelial junctions in leukocyte extravasation and vascular permeability. Ann N Y Acad Sci 1257:184–192

    Article  CAS  PubMed  Google Scholar 

  • Vestweber D, Wessel F, Nottebaum AF (2014) Similarities and differences in the regulation of leukocyte extravasation and vascular permeability. Semin Immunopathol 36:177–192

    Article  CAS  PubMed  Google Scholar 

  • Waschke J, Drenckhahn D, Adamson RH, Curry FE (2004) Role of adhesion and contraction in Rac 1-regulated endothelial barrier function in vivo and in vitro. Am J Physiol Heart Circ Physiol 287:H704–H711

    Article  CAS  PubMed  Google Scholar 

  • Wayland H, Johnson PC (1967) Erythrocyte velocity measurement in microvessels by a two-slit photometric method. J Appl Physiol 22:333–337

    Article  CAS  PubMed  Google Scholar 

  • Weis SM (2008) Vascular permeability in cardiovascular disease and cancer. Curr Opin Hematol 15:243–249

    Article  CAS  PubMed  Google Scholar 

  • Weis S, Cui J, Barnes L, Cheresh D (2004) Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 167:223–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wessel F, Winderlich M, Holm M, Frye M, Rivera-Galdos R, Vockel M, Linnepe R, Ipe U, Stadtmann A, Zarbock A, Nottebaum AF, Vestweber D (2014) Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin. Nat Immunol 15:223–230

    Article  CAS  PubMed  Google Scholar 

  • Wick N, Saharinen P, Saharinen J, Gurnhofer E, Steiner CW, Raab I, Stokic D, Giovanoli P, Buchsbaum S, Burchard A, Thurner S, Alitalo K, Kerjaschki D (2007) Transcriptomal comparison of human dermal lymphatic endothelial cells ex vivo and in vitro. Physiol Genomics 28:179–192

    Article  CAS  PubMed  Google Scholar 

  • Wiesmann C, Fuh G, Christinger HW, Eigenbrot C, Wells JA, De Vos AM (1997) Crystal structure at 1.7 a resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell 91:695–704

    Article  CAS  PubMed  Google Scholar 

  • Zheng W, Nurmi H, Appak S, Sabine A, Bovay E, Korhonen EA, Orsenigo F, Lohela M, D'amico G, Holopainen T, Leow CC, Dejana E, Petrova TV, Augustin HG, Alitalo K (2014) Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions. Genes Dev 28:1592–1603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University and Science for Life Laboratory, Uppsala, Sweden

    Lakshmi Venkatraman & Lena Claesson-Welsh

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  1. Lakshmi Venkatraman
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  2. Lena Claesson-Welsh
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Correspondence to Lena Claesson-Welsh .

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  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

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Venkatraman, L., Claesson-Welsh, L. (2019). The Role of VEGF in Controlling Vascular Permeability. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_37

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