Endothelial cell functions, primarily involving regulated mediator secretion or altered surface protein expression, are vital for normal homeostasis. Endothelial cells secrete the potent vasodilator and anti-platelet agent prostacyclin and nitric oxide, and also the potent vasoconstrictor peptide endothelin-1; they control the selective adhesion and emigration of leukocytes from the bloodstream; and they are the source of circulating von Willebrand factor, tissue plasminogen activator and type 1 plasminogen activator inhibitor. The properties of healthy endothelium ensure that an antithrombotic and anticoagulant balance is maintained in the bloodstream, and provide a tonic vasodilator action that controls blood flow and pressure on a minute-to-minute basis. Disturbances of normal endothelial function are strongly implicated in the pathogenesis of atherosclerosis and autoimmune vasculitic diseases including lupus.
Beck L , D'Amore PA.Vascular development:cellular and molecular recognition . FASEB J1997;11: 365–373 .
4.
Rees DD , Palmer RMJ , Moncada S . Role of endothelium-derived nitric oxide in the regulation of blood pressure . Proc Nat Acad Sci USA1989;86: 3375–3378 .
5.
Huang PL , Huang Z , Mashimo H et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase . Nature1995;377: 239–242 .
6.
Fisslthaler B , Popp R , Kiss L et al. Cytochrome P4502C is an EDHF synthase in coronary arteries . Nature1999;401: 493–497 .
7.
Maxwell AJ , Tsao PS , Cooke JP . Modulation of the nitric oxide synthase pathway in atherosclerosis . Exp Physiol1998;83: 573–584 .
8.
Miyazaki H , Matsuoka H , Cooke JP et al. Endogenous nitric oxide synthase inhibitor:a novel marker of atherosclerosis . Circulation1999;99: 1141–1146 .
9.
Carter TD , Pearson JD . Regulation of prostacyclin synthesis in endothelial cells . News Physiol Sci1992;7: 64–69 .
10.
Wheeler-Jones CPD , May MJ , Houliston RA , Pearson JD.Inhibition of MAP kinase kinase (MEK) blocks endothelial PGI2 release but has no effect on von Willebrand Factor secretion or E-selectin expression . FEBS Lett1996;388: 180–184 .
11.
Ayajiki K , Kindermann M , Hecker M et al. Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress induced nitric oxide production in native endothelial cells . Circ Res1996;78: 750–758 .
12.
Fulton D , Gratton J-P , McCabe TJ et al. Regulation of endotheliumderived nitric oxide production by the protein kinase Akt . Nature1999;399: 597–601 .
13.
Dimmeler S , Fleming I , Fisslthaler B et al. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation . Nature1999;399: 601–605 .
14.
Rizzo V , Sung A , Oh P , Schnitzer JE . Rapid mechanotransduction in situ at the luminal cell surface of vascular endothelium and its caveolae . J Biol Chem1998;273: 26323–26329 .
15.
Hayne WG , Webb DJ . Endothelin as a regulator of cardiovascular function in health and disease . J Hypertens1998;16: 1081–1098 .
16.
Benigni A , Remuzzi G . Endothelin antagonists . Lancet1999;353: 133–138 .
17.
Springer TA . Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration . Annu Rev Physiol1995;57: 857–887 .
18.
Toothill VJ , van Mourik JA , Niewenhuis HK et al. Characterization of the enhanced adhesion of neutrophil leukocytes to thrombin-stimulated endothelial cells . J Immunol1990;145: 283–296 .
19.
Bevilacqua MP , Stengelin S , Gimbrone MA Jr , Seed B.Endothelial leukocyte adhesion molecule 1:an inducible receptor for neutrophils related to complement regulatory proteins and lectins . Science1989;243: 1160–1165 .
20.
Foxall C , Watson SR , Dowbenko D et al. The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewisx oligosaccharide . J Cell Biol1992;117: 895–902 .
21.
Tedder TF , Isaacs CM , Ernst TJ et al. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1 . J Exp Med1989;170: 123–133 .
22.
Ley K , Gaehtgens C , Fennie C et al. Lectin-like adhesion molecule-1 mediates leukocyte rolling in mesenteric venules in vivo . Blood1991;77: 2553–2555 .
23.
Weber C , Alon R , Moser B , Springer TA . Sequential regulation of a4b1 and a5b1 integrin avidity by CC chemokines in monocytes:implications for transendothelial chemotaxis . J Cell Biol1996;134: 1063–1073 .
24.
Elices MJ , Osborn L , Takada Y et al. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4=fibronectin binding site . Cell1990;60: 577–584 .
25.
Marui N , Offerman NK , Swerlick R et al. VCAM-1 gene transcription and expression is regulated through an antioxidant sensitive mechanism in human vascular endothelial cells . J Clin Invest1993;92: 1866–1874 .
26.
Cushing SD , Berliner JA , Valente AJ et al. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells . Proc Nat Acad Sci USA1990;87: 5134–5138 .
27.
Newman PJ . The biology of PECAM-1 . J Clin Invest1997;99: 3–8 .
28.
Wagner DD . Cell biology of von Willebrand factor . Annu Rev Cell Biol1990;6: 217–246 .
29.
Frearson JA , Harrison P , Scrutton MC , Pearson JD . Differential regulation of von Willebrand factor exocytosis and prostacylin synthesis in electropermeabilised endothelial cell monolayers . Biochem J1995;309: 473–479 .
30.
Pottinger BE , Read RC , Paleolog EM , Pearson JD . Von Willebrand factor is an acute phase reactant in man . Thromb Res1989;53: 387–394 .
31.
Paleolog EM , Crossman DC , McVey JH , Pearson JD . Differential regulation by cytokines of constitutive and stimulated secretion of vWf from endothelial cells . Blood1990;75: 688–695 .
Freedman JE , Sauter R , Battinelli EM et al. Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene . Circ Res1999;84: 1416–1421 .
34.
Nakayama T , Soma M , Rahmutula D et al. Nonsense mutation of prostacyclin synthase gene in a family . Lancet1997;349: 1887–1888 .
35.
Hollenberg MD.Protease-mediated signalling:new paradigms for cell regulation and drug development . Trends Pharmacol Sci1996;17: 3–6 .
36.
Marcum JA , Kenny JB , Rosenberg RD . Acceleration of thrombinantithrombin complex formation in rat hindquarters via heparin-like molecules bound to the endothelium . J Clin Invest1984;74: 341–350 .
37.
Esmon CT . Thrombomodulin as model of molecular mechanisms that modulate protease specificity and function at the vessel surface . FASEB J1995;9: 946–955 .
38.
Laszik Z , Mitro A , Taylor FB et al. Human protein C receptor is present primarily on endothelium of large blood vessels–implications for the control of the Protein C pathway . Circulation1997;96: 3633–3640 .
39.
Salomaa V , Matei C , Aleksic N et al. Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) study:a case-cohort study . Lancet1999;353: 1729–1734 .
40.
Booth NA , Bennett B . Fibrinolysis and thrombosis . BaillieÁre's Clin Haematol1994;7: 559–572 .
41.
Emeis JJ , van den Eijnden-Schrauwen Y , van den Hoogen cm et al. An endothelial storage granule for tissue-type plasminogen activator . J Cell Biol1997;139: 245–256 .
42.
Schleef RR , Bevilacqua MP , Sawdey M et al. Interleukin 1 and tumor necrosis factor activation of vascular endothelium:effects on plasminogen activator inhibitor and tissue-type plasminogen activator . J Biol Chem1988;263: 5797–5803 .
43.
Allison BA , Nilsson L , Karpe F et al. Effects of native, triglycerideenriched and oxidatively modified LDL on plasminogen activator inhibitor-1 expression in human endothelial cells . Arterioscl Thromb Vasc Biol1999;19: 1354–1360 .
44.
Davie EW , Fujikawa K , Kisiel W . The coagulation cascade:initiation, maintenance and regulation . Biochemistry1991;30: 10363–10370 .
45.
Rivers RP , Cattermole H E , Wright I . The expression of surface tissue factor apoprotein by blood monocytes in the course of infections in early infancy . Pediatr Res1992;31: 567–573 .
