Skip to main content
SpringerLink
Log in

Soluble Vascular Endothelial (VE)-Cadherin: Toward a Marker of Endothelial Dysfunction

  • Chapter
  • First Online:
Molecular Mechanisms of Angiogenesis

Abstract

Endothelial dysfunction is a hallmark for vascular diseases. It is often seen in patients with coronary artery disease, diabetes, hypertension, rheumatoid arthritis, systemic vasculitis, and cancer. Identification of serologic markers that are associated with disease activity to diagnose or predict relapse is a challenging task. At the cellular level, endothelial dysfunction is the result of activation of several signaling pathways due to increased levels of cytokines associated with the disease. Endothelium integrity is dependent upon the adhesive function of the major molecule located at endothelial adherens junctions called vascular endothelial (VE)-cadherin. As in the case of other members of the cadherin family, VE-cadherin is able to mediate homotypic types of endothelial cellular interactions in a Ca2+-dependent manner and to link the underlying cytoskeleton. In conditions mimicking endothelial cell activation, the junctional complexes are subjected to posttranslational modifications such as phosphorylations or proteolysis reactions mediated by kinases and proteases, respectively, which are supposed to weaken the junctional strength. This chapter summarizes recent studies on VE-cadherin structural modifications in endothelial biology having potential applications in disease management and patient care.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Allingham MJ, van Buul JD, Burridge K (2007) ICAM-1-mediated, Src- and Pyk2-dependent vascular endothelial cadherin tyrosine phosphorylation is required for leukocyte transendothelial migration. J Immunol 179(6):4053–4064

    Article  CAS  PubMed  Google Scholar 

  • Andriopoulou P, Navarro P, Zanetti A, Lampugnani MG, Dejana E (1999) Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. Arterioscler Thromb Vasc Biol 19:2286–2297

    Article  CAS  PubMed  Google Scholar 

  • Bauchet L, Mathieu-DaudĂ© H, Fabbro-Peray P, Rigau V, Fabbro M, Chinot O et al (2010) Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004. Neuro Oncol 12:725–735

    Article  PubMed Central  PubMed  Google Scholar 

  • Baumeister U, Funke R, Ebnet K, Vorschmitt H, Koch S, Vestweber D (2005) Association of Csk to VE-cadherin and inhibition of cell proliferation. EMBO J 24(9):1686–1695

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beaufort N, Corvazier E, Mlanaoindrou S, de Bentzmann S, Pidard D (2013) Disruption of the endothelial barrier by proteases from the bacterial pathogen pseudomonas aeruginosa: implication of matrilysis and receptor cleavage. PLoS One 19:8(9)

    Google Scholar 

  • Bouillet L, Ponard D, Drouet C, Massot C (2002) Non-allergic angioedema: update. Rev Med Interne 23(6):533–541

    Article  CAS  PubMed  Google Scholar 

  • Bouillet L, Mannic T, Arboleas M, Subileau M, Massot C, Drouet C, Huber P, Vilgrain I (2011) Hereditary angioedema: keyrole for kallikrein and bradykinin in vascular endothelial-cadherin cleavage and edema formation. J Allergy Clin Immunol 128(1):232–234

    Article  PubMed  Google Scholar 

  • Campbell LA, Lee AW, Rosenfeld ME, Kuo CC (2013) Chlamydia pneumoniae induces expression of pro-atherogenic factors through activation of the lectin-like oxidized LDL receptor-1. Pathog Dis 69(1):1–6

    CAS  Google Scholar 

  • Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oostuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E (1999) Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98:147–157

    Article  CAS  PubMed  Google Scholar 

  • Cascone I, Giraudo E, Caccavari F, Napione L, Bertotti E, Collard JG, Serini G, Bussolino F (2003) Temporal and spatial modulation of Rho GTPases during in vitro formation of capillary vascular network. Adherens junctions and myosin light chain as targets of Rac1 and RhoA. J Biol Chem 278:50702–50713

    Article  CAS  PubMed  Google Scholar 

  • Cicardi M, Zingale L (2004) Clinical manifestation of hereditary angioedema. J Allergy Clin Immunol 114:S55–S59

    Google Scholar 

  • Corada M, Mariotti M, Thurston G, Smith K, Kunkel R, Brockhaus M, Lampugnani MG, Martin-Padura I, Stoppacciaro A, Ruco L, McDonald DM, Ward PA, Dejana E (1999) Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci U S A 96:9815–9820

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Daniel JM, Reynolds AB (1997) Tyrosine phosphorylation and cadherin/catenin function. Bioessays 19(10):883–891

    Article  CAS  PubMed  Google Scholar 

  • Davis AE III (2005) The physiopathology of hereditary angioedema. Clin Immunol 114:3–9

    Article  CAS  PubMed  Google Scholar 

  • Diamant M, Tushuizen ME, Sturk A, Nieuwland R (2004) Cellular microparticles: new players in the field of vascular disease? Eur J Clin Invest 34:392–401

    Article  CAS  PubMed  Google Scholar 

  • Dreymueller D, Pruessmeyer J, Groth E, Ludwig A (2012) The role of ADAM-mediated shedding in vascular biology. Eur J Cell Biol 91(6–7):472–485

    Article  CAS  PubMed  Google Scholar 

  • Dvorak HF (1990) Leaky tumor vessels: consequences for tumor stroma generation and for solid tumor therapy. Prog Clin Biol Res 354A:317–330

    CAS  PubMed  Google Scholar 

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Article  CAS  PubMed  Google Scholar 

  • George JM, Bhat R, Pai KM, S A, Jeganathan J (2013) The carotid intima media thickness: a predictor of the clinical coronary events. J Clin Diagn Res 7(6):1082–1085

    Google Scholar 

  • Goeb V, Dieude P, Daveau R, Thomas-L’Otellier M, Jouen F, Hau F, Boumier P, Tron F, Gilbert D, Fardellone P, CornĂ©lis F, Le LoĂ«t X, Vittecoq O (2008) Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anticitrullinated protein antibodies to very early rheumatoid arthritis diagnosis. Rheumatology (Oxford) 47:1208–1212

    Article  CAS  Google Scholar 

  • Gory-FaurĂ© S, Prandini MH, Pointu H, Roullot V, Pignot-Paintrand I, Vernet M, Huber P (1999) Role of vascular endothelial-cadherin in vascular morphogenesis. Development 126:2093–2102

    PubMed  Google Scholar 

  • Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E et al (2005) Prevalence of rheumatoid arthritis in France: 2001. Ann Rheum Dis 64(10):1427–1430

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hirata Y, Nagata D, Suzuki E, Nishimatsu H, Suzuki JI, Nagai R (2010) Diagnosis and treatment of endothelial dysfunction in cardiovascular disease: a review. Int Heart J 51(1):1–6

    Article  CAS  PubMed  Google Scholar 

  • Hudry-Clergeon H, Stengel D, Ninio E, Vilgrain I (2005) Platelet-activating factor increases VE-cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3′-kinase. FASEB J 19(6):512–520

    Article  CAS  PubMed  Google Scholar 

  • Issekutz TB (1995) In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin. J Immunol 154(12):6533–6540

    CAS  PubMed  Google Scholar 

  • Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL et al (1994) Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 37:187–192

    Article  CAS  PubMed  Google Scholar 

  • Kouklis P, Konstantoulaki M, Malik AB (2003) VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells. J Biol Chem 278:16230–16236

    Article  CAS  PubMed  Google Scholar 

  • Kramer HR, Giles JT (2011) Cardiovascular disease risk in rheumatoid arthritis: progress, debate, and opportunity. Arthritis Care Res (Hoboken) 63(4):484–499

    Article  Google Scholar 

  • Lambeng N, Wallez Y, Rampon C, Cand F, Christe G, Gulino-Debrac D et al (2005) Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues. Circ Res 96(3):384–391

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lampugnani MG, Corada M, Caveda L, Breviario F, Ayalon O, Geiger B et al (1995) The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha-catenin with vascular endothelial cadherin (VE-cadherin). J Cell Biol 129:203–217

    Article  CAS  PubMed  Google Scholar 

  • Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM, Tedgui A (2000) Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 101:841–843

    Article  CAS  PubMed  Google Scholar 

  • Mariette X, Gottenberg JE, Ravaud P, Combe B (2011) Registries in rheumatoid arthritis and autoimmune diseases: data from the French registries. Rheumatology (Oxford) 50(1):222–229

    Article  Google Scholar 

  • Meerschaert J, Furie MB (1995) The adhesion molecules used by monocytes for migration across endothelium include CD11a/CD18, CD11b/CD18, and VLA-4 on monocytes and ICAM-1, VCAM-1, and other ligands on endothelium. J Immunol 154(8):4099–4112

    CAS  PubMed  Google Scholar 

  • Navaratna D, McGuire PG, Menicucci G, Das A (2007) Proteolytic degradation of VE-cadherin alters the blood-retinal barrier in diabetes. Diabetes 56(9):2380–2387

    Article  CAS  PubMed  Google Scholar 

  • Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A (1998) Plasma bradykinin in angioedema. Lancet 351:1693–1697

    Article  CAS  PubMed  Google Scholar 

  • Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22–27

    Article  CAS  PubMed  Google Scholar 

  • Pisetsky DS, Ullal AJ, Gauley J, Ning TC (2012) Microparticles as mediators and biomarkers of rheumatic disease. Rheumatology (Oxford) 51(10):1737–1746

    Article  CAS  Google Scholar 

  • Potter MD, Barbero S, Cheresh DA (2005) Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state. J Biol Chem 280(36):31906–31912

    Article  CAS  PubMed  Google Scholar 

  • Prado GN, Taylor L, Zhou X, Ricupero D, Mierke DF, Polgar P (2002) Mechanisms regulating the expression, self maintenance and signalling-function of the bradykinin B2 and B1 receptors. J Cell Physiol 193:275–286

    Article  CAS  PubMed  Google Scholar 

  • Prasad A, Zhu J, Halcox JP, Waclawiw MA, Epstein SE, Quyyumi AA (2002) Predisposition to atherosclerosis by infections: role of endothelial dysfunction. Circulation 106(2):184–190

    Article  PubMed  Google Scholar 

  • Rabiet MJ, Plantier JL, Rival Y, Genoux Y, Lampugnani MG, Dejana E (1996) Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. Arterioscler Thromb Vasc Biol 16:488–496

    Article  CAS  PubMed  Google Scholar 

  • Rajagopalan S, Somers EC, Brook RD, Kehrer C, Pfenninger D, Lewis E, Chakrabarti A, Richardson BC, Shelden E, McCune WJ, Kaplan MJ (2004) Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood 103:3677–3683

    Article  CAS  PubMed  Google Scholar 

  • Schalkwijk CG, Poland DC, van Dijk W, Kok A, Emeis JJ, Dräger AM, Doni A, van Hinsbergh VW, Stehouwer CD (1999) Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia 42(3):351–357

    Article  CAS  PubMed  Google Scholar 

  • Schiffrin EL (2001) A critical review of the role of endothelial factors in the pathogenesis of hypertension. J Cardiovasc Pharmacol 38(Suppl 2):S3–S6

    Article  CAS  PubMed  Google Scholar 

  • Schulz B, Pruessmeyer J, Maretzky T, Ludwig A, Blobel CP, Saftig P, Reiss K (2008) ADAM10 regulates endothelial permeability and T-Cell transmigration by proteolysis of vascular endothelial cadherin. Circ Res 102(10):1192–1201

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376(9746):1094–1108

    Article  PubMed  Google Scholar 

  • SidibĂ© A, Mannic T, Arboleas M, Subileau M, Gulino-Debrac D, Bouillet L, Jan M, Vandhuick T, Le LoĂ«t X, Vittecoq O, Vilgrain I (2012) Soluble VE-cadherin in rheumatoid arthritis patients correlates with disease activity: evidence for tumor necrosis factor α-induced VE-cadherin cleavage. Arthritis Rheum 64(1):77–87

    Article  PubMed  Google Scholar 

  • Smolen JS, Steiner G (2003) Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2(6):473–488

    Article  CAS  PubMed  Google Scholar 

  • Soeki T, Tamura Y, Shinohara H, Sakabe K, Onose Y, Fukuda N (2004) Elevated concentration of solublevascularendothelialcadherinisassociatedwithcoronaryatherosclerosis. Circ J 68(1):1–5

    Article  CAS  PubMed  Google Scholar 

  • Spillmann D, Witt D, Lindahl U (1998) Defining the interleukin-8-binding domain of heparansulfate. J Biol Chem 273(25):15487–15493

    Article  CAS  PubMed  Google Scholar 

  • Suryawanshi A, Veiga-Parga T, Reddy PB, Rajasagi NK, Rouse BT (2012) IL-17A differentially regulates corneal vascular endothelial growth factor (VEGF)-A and soluble VEGF receptor 1 expression and promotes corneal angiogenesis after herpes simplex virus infection. J Immunol 188(7):3434–3446

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Venkiteswaran K, Xiao K, Summers S, Calkins CC, Vincent PA, Pumiglia K, Kowalczyk AP (2002) Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and beta-catenin. Am J Physiol 283:C811–C821

    Article  CAS  Google Scholar 

  • Vercellotti GM (1990) Proinflammatory and procoagulant effects of herpes simplex infection on human endothelium. Blood Cells 16(1):209–215, discussion 215–6. Review. Erratum in: Blood Cells. 1991, 17(2):442

    CAS  PubMed  Google Scholar 

  • Vestweber D, Winderlich M, Cagna G, Nottebaum AF (2009) Cell adhesion dynamics at endothelial junctions: VE-cadherin as a major player. Trends Cell Biol 19(1):8–15

    Article  CAS  PubMed  Google Scholar 

  • Vilgrain I, SidibĂ© A, Polena H, Cand F, Mannic T, Arboleas M, Boccard S, Baudet A, Gulino-Debrac D, Bouillet L, Quesada JL, Mendoza C, Lebas JF, Pelletier L, Berger F (2013) Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker. PLoS One 16:8(12)

    Google Scholar 

  • Villasante A, Pacheco A, Pau E, Ruiz A, Pellicer A, Garcia-Velasco JA (2008) Soluble vascular endothelial-cadherin levels correlate with clinical and biological aspects of severe ovarian hyperstimulation syndrome. Hum Reprod 23(3):662–667

    Article  CAS  PubMed  Google Scholar 

  • Vittet D, Buchou T, Schweitzer A, Dejana E, Huber P (1997) Targeted null-mutation in the vascular endothelial-cadherin gene impairs the organization of vascular-like structures in embryoid bodies. Proc Natl Acad Sci U S A 94(12):6273–6278

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wallez Y, Cand F, Cruzalegui F, Wernstedt C, Souchelnytskyi S, Vilgrain I, Huber P (2007) Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site. Oncogene 26(7):1067–1077

    Article  CAS  PubMed  Google Scholar 

  • Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 4:278–299

    PubMed Central  PubMed  Google Scholar 

  • Zhang RY, Liu YY, Li L, Cui W, Zhao KJ, Huang WC, Gu XW, Liu W, Wu J, Min D, Mao EQ, Tang YQ (2010) Increased levels of soluble vascular endothelial cadherin are associated with poor outcome in severe sepsis. J Int Med Res 38(4):1497–1506

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Geneva, Geneva, CH-1211, Switzerland

    Adama Sidibé & Tiphaine Mannic

  2. Biology of Cancer and Infection, INSERM, Unit 1036, Grenoble, F-38054, France

    Helena Polena, Barry Stidder, Laurence Bouillet & Isabelle Vilgrain

  3. Biology of Cancer and Infection, UJF-Grenoble 1, Grenoble, F-38041, France

    Helena Polena, Barry Stidder, Laurence Bouillet & Isabelle Vilgrain

  4. Biology of Cancer and Infection, CEA, DSV/iRTSV, Grenoble, F-38054, France

    Helena Polena, Barry Stidder, Laurence Bouillet & Isabelle Vilgrain

  5. Division of Internal Medicine, Grenoble University Hospital, Grenoble, F-38043, France

    Laurence Bouillet

  6. INSERM Unité 1036, Institute of Life Sciences Research and Technologies (iRTSV), Joseph Fourier University, CEA Grenoble, 17, rue des Martyrs, Grenoble, 38054, France

    Isabelle Vilgrain

Authors
  1. Adama Sidibé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helena Polena
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiphaine Mannic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Barry Stidder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurence Bouillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Isabelle Vilgrain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabelle Vilgrain .

Editor information

Editors and Affiliations

  1. UMR 1036, Biologie du Cancer et de l’Infection, Institut de Recherches en Technologies et Sciences pour le Vivant, Université Grenoble-Alpes, Grenoble, France

    Jean-Jacques Feige

  2. Institute for Research on Cancer and aging of Nice (IRCAN), University of Nice Sophia Antipolis, Nice, France

    Gilles Pagès

  3. CNRS UMR8161, Institut Pasteur de Lille, Institut de Biologie de Lille, Lille, France

    Fabrice Soncin

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag France

About this chapter

Cite this chapter

Sidibé, A., Polena, H., Mannic, T., Stidder, B., Bouillet, L., Vilgrain, I. (2014). Soluble Vascular Endothelial (VE)-Cadherin: Toward a Marker of Endothelial Dysfunction. In: Feige, JJ., Pagès, G., Soncin, F. (eds) Molecular Mechanisms of Angiogenesis. Springer, Paris. https://doi.org/10.1007/978-2-8178-0466-8_23

Download citation

Publish with us

Policies and ethics

Search

Navigation