Skip to main content

Sites of Injury: The Endothelium

  • Chapter
  • First Online:
New Solutions for the Heart

Abstract

An estimated 6 × 1013 endothelial cells form the inner surface of blood vessels in man. As such, in an adult human being they cover a total area of approximately 3,000 m2 and have a total volume comparable to that of the liver (Huttner and Gabbiani 1982; Münzel et al. 2008). Traditionally, the endothelium has been assumed to be a passive barrier between the blood and the surrounding tissue; however, over the past 2–3 decades numerous additional roles for the endothelium have been described. These findings challenge the concept of the endothelium as a passive interface and leads to the notion of the endothelium being a highly active organ involved in the regulation and modulation of a vast number of physiological and pathophysiological processes. Endothelial cells are essential in the regulation of vascular tone, control of transendothelial movement of fluid, solutes and macromolecules, modulation of inflammation and leukocyte adhesion, promotion and inhibition of growth of new blood vessels and regulation of blood fluidity and platelet aggregation, fibrinolysis and coagulation.

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

Access this chapter

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
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
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

  • Aird WC (2003) The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101: 3765–3777

    Article  PubMed  CAS  Google Scholar 

  • Aktan F (2004) iNOS-mediated nitric oxide production and its regulation. Life Sci 75: 639–653

    Article  PubMed  CAS  Google Scholar 

  • Austrup F, Vestweber D, Borges E, Löhning M, Bräuer R, Herz U, Renz H, Hallmann R, Scheffold A, Radbruch A, Hamann A (1997) P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues. Nature 385: 81–83

    Article  PubMed  CAS  Google Scholar 

  • Becker BF, Kupatt C, Massoudy P, Zahler S (2000) Reactive oxygen species and nitric oxide in myocardial ischemia and reperfusion. Z Kardiol 89 Suppl 9: IX/88–91

    Google Scholar 

  • Bhandari V, Choo-Wing R, Lee CG, Zhu Z, Nedrelow JH, Chupp GL, Zhang X, Matthay MA, Ware LB, Homer RJ, Lee PJ, Geick A, de Fougerolles AR, Elias JA (2006) Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nat Med 12: 1286–1293

    Article  PubMed  CAS  Google Scholar 

  • Birch KA, Pober JS, Zavoico GB, Means AR, Ewenstein BM (1992) Calcium/calmodulin transduces thrombin-stimulated secretion: studies in intact and minimally permeabilized human umbilical vein endothelial cells. J Cell Biol 118: 1501–1510

    Article  PubMed  CAS  Google Scholar 

  • Birdi I, Angelini GD, Bryan AJ (1997) Biochemical markers of myocardial injury during cardiac operations. Ann Thorac Surg 63: 879–884

    Article  PubMed  CAS  Google Scholar 

  • Bombeli T, Karsan A, Tait JF, Harlan JM (1997) Apoptotic vascular endothelial cells become procoagulant. Blood 89: 2429–2442

    PubMed  CAS  Google Scholar 

  • Busse R, Fleming I (2006) Vascular endothelium and blood flow. Handb Exp Pharmacol 176: 43–78

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekar B, Mitchell DH, Colston JT, Freeman GL (1999) Regulation of CCAAT/Enhancer binding protein, interleukin-6, interleukin-6 receptor, and gp130 expression during myocardial ischemia/reperfusion. Circulation 99: 427–433

    Article  PubMed  CAS  Google Scholar 

  • Chaplin DD (2002) Cell cooperation in development of eosinophil-predominant inflammation in airways. Immunol Res 26: 55–62

    Article  PubMed  CAS  Google Scholar 

  • Clark PR, Manes TD, Pober JS, Kluger MS. (2007) Increased ICAM-1 expression causes endothelial cell leakiness, cytoskeletal reorganization and junctional alterations. J Invest Dermatol 127: 762–774

    Article  PubMed  CAS  Google Scholar 

  • Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D (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

    Article  PubMed  CAS  Google Scholar 

  • Cotran RS, Pober JS (1989) Effects of cytokines on vascular endothelium: their role in vascular and immune injury. Kidney Int 35: 969–975

    Article  PubMed  CAS  Google Scholar 

  • Coughlin CM, Salhany KE, Gee MS, LaTemple DC, Kotenko S, Ma X, Gri G, Wysocka M, Kim JE, Liu L, Liao F, Farber JM, Pestka S, Trinchieri G, Lee WM (1998) Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9: 25–34

    Article  PubMed  CAS  Google Scholar 

  • De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA Jr, Shin WS, Liao JK (1995) Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 96: 60–68

    Article  PubMed  Google Scholar 

  • Dellas C, Loskutoff DJ (2005) Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 93: 631–640

    PubMed  CAS  Google Scholar 

  • Deten A, Volz HC, Holzl A, Briest W, Zimmer HG (2003) Effect of propranolol on cardiac cytokine expression after myocardial infarction in rats. Mol Cell Biochem 251: 127–137

    Article  PubMed  CAS  Google Scholar 

  • Doukas J, Pober JS (1990) IFN-gamma enhances endothelial activation induced by tumor necrosis factor but not IL-1. J Immunol 145: 1727–1733

    PubMed  CAS  Google Scholar 

  • Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20: 4368–4380

    Article  PubMed  CAS  Google Scholar 

  • Engelman DT, Watanabe M, Engelman RM, Rousou JA, Flack JE 3rd, Deaton DW, Das DK (1995) Constitutive nitric oxide release is impaired after ischemia and reperfusion. J Thorac Cardiovasc Surg 110:1047–1053

    Article  PubMed  CAS  Google Scholar 

  • Félétou M, Vanhoutte PM (2006) Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 291: H985–H1002

    Article  PubMed  Google Scholar 

  • Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG (2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 12: 235–239

    Article  PubMed  CAS  Google Scholar 

  • Fleming I, Busse R (2003) Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 284: R1–R12

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83: 1774–1777

    Article  PubMed  CAS  Google Scholar 

  • Greeno EW, Bach RR, Moldow CF (1996) Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest 75: 281–289

    PubMed  CAS  Google Scholar 

  • Griendling KK, FitzGerald GA (2003a) Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS. Circulation 108: 1912–1916

    Article  PubMed  Google Scholar 

  • Griendling KK, FitzGerald GA (2003b) Oxidative stress and cardiovascular injury: Part II: animal and human studies. Circulation 108: 2034–2040

    Article  PubMed  Google Scholar 

  • Guzik TJ, Korbut R, Adamek-Guzik T (2003) Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol 54: 469–487

    PubMed  CAS  Google Scholar 

  • Hancock WW, Kraft N, Atkins RC (1982) The immunohistochemical demonstration of major histocompatibility antigens in the human kidney using monoclonal antibodies. Pathology 14: 409–414

    Article  PubMed  CAS  Google Scholar 

  • Hart DN, Fuggle SV, Williams KA, Fabre JW, Ting A, Morris PJ (1981) Localization of HLA-ABC and DR antigens in human kidney. Transplantation 31: 428–433

    Article  PubMed  CAS  Google Scholar 

  • Huttner I, Gabbiani G (1982) Vascular endothelium: recent advances and unanswered questions. Lab Invest 47: 409–411

    PubMed  CAS  Google Scholar 

  • Ibengwe JK, Suzuki H (1986) Changes in mechanical responses of vascular smooth muscles to acetylcholine, noradrenaline and high-potassium solution in hypercholesterolemic rabbits. Br J Pharmacol 87: 395–402

    Article  PubMed  CAS  Google Scholar 

  • Joris I, Cuénoud HF, Doern GV, Underwood JM, Majno G (1990) Capillary leakage in inflammation. A study by vascular labeling. Am J Pathol 137: 1353–1363

    PubMed  CAS  Google Scholar 

  • Kerr JF (2002) History of the events leading to the formulation of the apoptosis concept. Toxicology 181–182: 471–474

    Article  PubMed  Google Scholar 

  • Kim I, Oh JL, Ryu YS, So JN, Sessa WC, Walsh K, Koh GY (2002) Angiopoietin-1 negatively regulates expression and activity of tissue factor in endothelial cells. FASEB J 16: 126–128

    PubMed  Google Scholar 

  • Kleinert H, Pautz A, Linker K, Schwarz PM (2004) Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500: 255–266

    Article  PubMed  CAS  Google Scholar 

  • Ley K, Reutershan J (2006) Leucocyte-endothelial interactions in health and disease. Handb Exp Pharmacol 176: 97–133

    Article  PubMed  CAS  Google Scholar 

  • Lorant DE, Patel KD, McIntyre TM, McEver RP, Prescott SM, Zimmerman GA (1991) Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol 115: 223–234

    Article  PubMed  CAS  Google Scholar 

  • Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P (1986) Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315: 1046–1051

    Article  PubMed  CAS  Google Scholar 

  • Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146: 3–15

    PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Matsumori A, Igata H, Ono K, Iwasaki A, Miyamoto T, Nishio R, Sasayama S (1999) High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity. Jpn Circ J 63: 934–940

    Article  PubMed  CAS  Google Scholar 

  • Middleton J, Neil S, Wintle J, Clark-Lewis I, Moore H, Lam C, Auer M, Hub E, Rot A (1997) Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91: 385–395

    Article  PubMed  CAS  Google Scholar 

  • Münzel T, Daiber A, Ullrich V, Mülsch A (2005) Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. Arterioscler Thromb Vasc Biol 25: 1551–1557

    Article  PubMed  Google Scholar 

  • Münzel T, Sinning C, Post F, Warnholtz A, Schulz E (2008) Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med 40: 180–196

    Article  PubMed  Google Scholar 

  • Naseem KM (2005) The role of nitric oxide in cardiovascular diseases. Mol Aspects Med 26: 33–65

    Article  PubMed  CAS  Google Scholar 

  • Nawroth PP, Stern DM (1986) Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 163: 740–745

    Article  PubMed  CAS  Google Scholar 

  • Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Petrache I, Birukova A, Ramirez SI, Garcia JG, Verin AD (2003) The role of the microtubules in tumor necrosis factor-alpha-induced endothelial cell permeability. Am J Respir Cell Mol Biol 28: 574–581

    Article  PubMed  CAS  Google Scholar 

  • Pfaff D, Fiedler U, Augustin HG (2006) Emerging roles of the Angiopoietin-Tie and the ephrin-Eph systems as regulators of cell trafficking. J Leukoc Biol 80: 719–726

    Article  PubMed  CAS  Google Scholar 

  • Pober JS, Lapierre LA, Stolpen AH, Brock TA, Springer TA, Fiers W, Bevilacqua MP, Mendrick DL, Gimbrone MA Jr (1987) Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin 1 species. J Immunol 138: 3319–3324

    PubMed  CAS  Google Scholar 

  • Pober JS, Cotran RS (1990) The role of endothelial cells in inflammation. Transplantation 50: 537–544

    Article  PubMed  CAS  Google Scholar 

  • Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7: 803–815

    Article  PubMed  CAS  Google Scholar 

  • Pomerantz BJ, Reznikov LL, Harken AH, Dinarello CA (2001) Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1beta. Proc Natl Acad Sci U S A 98: 2871–2876

    Article  PubMed  CAS  Google Scholar 

  • Prescott SM, Zimmerman GA, McIntyre TM (1984) Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sci USA 81: 3534–3538

    Article  PubMed  CAS  Google Scholar 

  • Price DT, Vita JA, Keaney JF Jr (2000) Redox control of vascular nitric oxide bioavailability. Antioxid Redox Signal 2: 919–935

    Article  PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RM, Moncada S (1987) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 92: 639–646

    Article  PubMed  CAS  Google Scholar 

  • Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45: 528–537

    Article  PubMed  CAS  Google Scholar 

  • Sawa Y, Ichikawa H, Kagisaki K, Ohata T, Matsuda H (1998) Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium. J Thorac Cardiovasc Surg 116: 511–517

    Article  PubMed  CAS  Google Scholar 

  • Sessa WC (2004) eNOS at a glance. J Cell Sci 117: 2427–2429

    Article  PubMed  CAS  Google Scholar 

  • Shibuya M, Claesson-Welsh L (2006) Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 312: 549–560

    Article  PubMed  CAS  Google Scholar 

  • Sodha NR, Clements RT, Sellke FW (2009) Vascular changes after cardiac surgery: role of NOS, COX, kinases, and growth factors. Front Biosci 14: 689–698

    Article  PubMed  CAS  Google Scholar 

  • Strieter RM (2005) Masters of angiogenesis. Nat Med 11: 925–927

    Article  PubMed  CAS  Google Scholar 

  • Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101: 948–954

    Article  PubMed  CAS  Google Scholar 

  • te Velthuis H, Jansen PG, Oudemans-van Straaten HM, Sturk A, Eijsman L, Wildevuur CR (1995) Myocardial performance in elderly patients after cardiopulmonary bypass is suppressed by tumor necrosis factor. J Thorac Cardiovasc Surg 110: 1663–1669

    Article  PubMed  CAS  Google Scholar 

  • Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD (2000) Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6: 460–463

    Article  PubMed  CAS  Google Scholar 

  • Tofukuji M, Metais C, Li J, Franklin A, Simons M, Sellke FW (1998) Myocardial VEGF expression after cardiopulmonary bypass and cardioplegia. Circulation 98(19 Suppl): II242–II246

    Google Scholar 

  • Verbeuren TJ, Jordaens FH, Zonnekeyn LL, Van Hove CE, Coene MC, Herman AG (1986) Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circ Res 58: 552–564

    Article  PubMed  CAS  Google Scholar 

  • Walker LN, Ramsay MM, Bowyer DE (1983) Endothelial healing following defined injury to rabbit aorta. Depth of injury and mode of repair. Atherosclerosis 47: 123–130

    Article  PubMed  CAS  Google Scholar 

  • Winquist RJ, Bunting PB, Baskin EP, Wallace AA (1984) Decreased endothelium-dependent relaxation in New Zealand genetic hypertensive rats. J Hypertens 2: 541–545

    Article  PubMed  CAS  Google Scholar 

  • Zhang R, Xu Y, Ekman N, Wu Z, Wu J, Alitalo K, Min W (2003) Etk/Bmx transactivates vascular endothelial growth factor 2 and recruits phosphatidylinositol 3-kinase to mediate the tumor necrosis factor-induced angiogenic pathway. J Biol Chem 278: 51267–51276

    Article  PubMed  CAS  Google Scholar 

  • Zou MH, Cohen R, Ullrich V (2004) Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium 11: 89–97

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag/Wien

About this chapter

Cite this chapter

Wojta, J. (2011). Sites of Injury: The Endothelium. In: Podesser, B., Chambers, D. (eds) New Solutions for the Heart. Springer, Vienna. https://doi.org/10.1007/978-3-211-85548-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-85548-5_4

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-85547-8

  • Online ISBN: 978-3-211-85548-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics