Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as Potential Marker of Atherosclerosis

Karlheinz Peter; Uta Weirich; Thomas K. Nordt; Johannes Ruef; Christoph Bode

doi:10.1055/s-0037-1615551

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(S 01): 38-43
DOI: 10.1055/s-0037-1615551

Commentaries

Schattauer GmbH

Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as Potential Marker of Atherosclerosis

Karlheinz Peter

¹From the Internal Medicine III, University of Freiburg

,

Uta Weirich

²Internal Medicine III, University of Heidelberg, Germany

,

Thomas K. Nordt

¹From the Internal Medicine III, University of Freiburg

,

Johannes Ruef

²Internal Medicine III, University of Heidelberg, Germany

,

Christoph Bode

¹From the Internal Medicine III, University of Freiburg

› Author Affiliations

Abstract

Summary

An increasing number of descriptive reports on soluble adhesion molecules and association with various diseases are published. Throughout these reports soluble adhesion molecules are identified as markers of inflammation. Since atherosclerosis demonstrates features of a chronic inflammatory disease, a potential association of soluble adhesion molecules with atherosclerosis has been postulated. However, conflicting results have been reported. One reason for this might be the differing definitions of atherosclerosis and patient groups. Besides the definition of atherosclerosis based on clinical symptoms, few reports use a direct quantification of atherosclerosis in their search for a marker of atherosclerosis. In those reports that quantify atherosclerosis, sVCAM-1 seems to be more specific for atherosclerosis than other markers. The serum level of sVCAM-1 appears to correlate with the extent of atherosclerosis and might allow for the detection of early stages of atherosclerosis. Large scale prospective studies will have to prove that sVCAM-1 can be used as a diagnostic tool for the detection of early stages of asymptomatic atherosclerosis and whether an early therapeutic intervention based on this approach is able to prevent progression and manifestation of the clinical sequelae of atherosclerosis.

Key words

Atherosclerosis - adhesion molecules - VCAM-1 - serum marker

Full Text

References

References
1 Ross R. Atherosclerosis - An inflammatory disease. New Engl J Med 1999; 304: 115-26.
2 Stemme S, Rymo L, Hansson GK. Polyclonal origin of T lymphocytes in human atherosclerotic plaques. Lab Invest 1991; 65: 654-60.
3 Libby P, Hansson GK. Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. Lab Invest 1991; 64: 5-15.
4 Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signaling. Nature 1998; 394: 200-3.
5 Netea MG, Demacker PN, Kullberg BJ, Boermann OC, Verhueren I, Stalenhoef AF, van der, Meer JW. Increased interleukin-1alpha and interleukin-1beta production by macrophages of low-density lipoprotein receptor knock-out mice stimulated with lipopolysaccharide is CD11c/CD18-receptor mediated. Immunology 1998; 95: 466-72.
6 Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994; 76: 301-14.
7 Kansas GS. Selectins and their ligands: current concepts and controversies. Blood 1996; 88: 3259-87.
8 Oxley SM, Sackstein R. Detection of an L-selectin ligand on a hematopoietic progenitor cell line. Blood 1994; 84: 3299-306.
9 Berg EL, McEvoy LM, Berlin C, Bargatze RF, Butcher EC. L-selectin-mediated lymphocyte rolling on MAdCAM-1. Nature 1993; 366: 695-8.
10 Suguri T, Kikuta A, Iwagaki H, Yoshino T, Tanaka N, Orita K. Increased plasma GlyCAM-1, a mouse L-lectin ligand, in response to an inflammatory stimulus. J Leukoc Biol 1996; 60: 593-7.
11 Joseph-Silverstein J, Silverstein RL. Cell adhesion molecules: an overview. Cancer Invest 1998; 16: 176-82.
12 Sako D, Chang XJ, Barone KM, Vachino G, White HM, Shaw G, Veldman GM, Bean KM, Ahern TJ, Furie B, Cummings DA, Larsen GR. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 1993; 75: 1179-86.
13 Steegmaier M, Levinovitz A, Isenmann S, Borges E, Lenter M, Kocher HP, Kleuser B, Vestweber D. The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor. Nature 1995; 373: 615-20.
14 Alon R, Kassner PD, Carr MW, Finger EB, Hemler ME, Springer TA. The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 1995; 128: 1243-53.
15 Berlin C, Bargatze RF, Campbell JJ, von Adrian UH, Szabo MC, Hasslen SR, Nelson RD, Berg EL, Erlandsen SL, Butcher EC. Alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 1995; 80: 413-22.
16 Diamond MS, Staunton DE, Marlin SD, Springer TA. Binding of the integrin MAC-1 (CD11b/CD18) to the third immunoglobin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell 1991; 65: 961-71.
17 Vonderheide RH, Tedder TF, Springer TA, Staunton DE. Residues within a conserved amino acid motif of domain 1 and 4 of VCAM-1 are required for binding to VLA-4. J Cell Biol 1994; 125: 215-22.
18 Leeuwenberg JF, Smeets EF, Neefjes JJ, Shaffer MA, Cinek T, Jeunhomme TM, Ahern TJ, Buurman WA. E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro. Immunology 1992; 77: 543-9.
19 Cybulsky MI, Gimbrone MA. Endothelial expression of mononuclear leukocyte adhesion molecule during atherogenesis. Science 1991; 251: 788-91.
20 Li H, Cybulsky MI, Gimbrone MA, Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb 1993; 13: 197-204.
21 O'Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D, McCarty J, Ferguson M, Hudkins K, Benjamin CD, Lobb R, Alpers CE. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 1993; 92: 945-51.
22 Davies MJ, Gordon JL, Gearing AJH, Pigott R, Woolf N, Katz D, Kyriaopoulos A. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Path 1993; 171: 223-9.
23 Johnson-Tidey RR, McGregor JL, Taylor PR, Poston RN. Increase in the adhesion molecule P-selectin in endothelium covering atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. Am J Pathol 1994; 144: 952-61.
24 O'Brien KD, McDonald TO, Chait A, Allen MD, Alpers CE. Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 1996; 93: 672-82.
25 Koskinen PK, Lemstrnm KB. Adhesion molecule P-selectin and vascular cell adhesion molecule-1 in enhanced heart allograft arteriosclerosis in the rat. Circulation 1997; 95: 191-6.
26 Nakashima Y, Raines EW, Plump AS, Breslow JL, Ross R. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the apoE-deficient mouse. Arterioscler Thromb Vasc Biol 1998; 18: 842-51.
27 Sakai A, Kume N, Nishi E, Tanoue K, Miyasaka M, Kita T. P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hyper-cholesterolemic rabbits before intimal accumulation of macrophages and T-lymphocytes. Arterioscler Thromb Vasc Biol 1997; 17: 310-6.
28 Kume N, Cybulsky MI, Gimbrone MA. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 1992; 90: 1138-44.
29 Khan BV, Parthasarathy SS, Alexander RW, Medford RM. Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells. J Clin Invest 1995; 95: 1262-70.
30 Marui N, Offerman MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, Alexander RW, Medford RM. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an anti-oxidant sensitive mechanism in human vascular endothelial cells. J Clin Invest 1993; 92: 1866-74.
31 Cockerill GW, Rye KA, Gamble JR, Vadas MA, Barter PJ. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 1987-94.
32 Allen S, Khan S, Al-Mohanna F, Batten P, Yacoub M. Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human endothelial cells. J Clin Invest 1998; 101: 1064-75.
33 Allen S, Khan S, Tam S, Koschinsky M, Taylor P, Yacoub M. Expression of adhesion molecules by Lp(a): a potential novel mechanism for its atherogenicity. FASEB J 1998; 12: 1765-76.
34 DeCaterina R, Cybulsky MI, Clinton SK, Gimbrone MA, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 1994; 14: 1829-36.
35 Weber C, Erl W, Pietsch A, Weber P. Aspirin inhibits nuclear factor (B mobilization and monocyte adhesion in stimulated human endothelial cells. Circulation 1995; 91: 1914-7.
36 Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506-12.
37 Abe Y, El-Masri B, Kimball KT, Pownall H, Reilly CF, Osmundsen K, Smith CW, Ballantyne CM. Soluble cell adhesion molecules in hypertrigly-ceridemia and potential significance on monocyte adhesion. Arterioscler Thromb Vasc Biol 1998; 18: 723-31.
38 Schleiffenbaum B, Spertini O, Tedder TF. Soluble L-selectin is present in human plasma at high levels and retains functional activity. J Cell Biol 1992; 119: 229-38.
39 Newman W, Beall DB, Carson CW, Hunder GG, Graben N, Randhawa ZI, Gopal TV, Wiener-Kronish L, Matthay MA. Soluble E-selectin is found in supernatants of activated endothelial cells and is elevated in the serum of patients with septic shock. J Immunol 1993; 150: 633-54.
40 Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 1995; 376: 517-9.
41 Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM, Boerwinkle E. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases. Circulation 1997; 96: 4219-25.
42 Pigott R, Dillon LP, Hemingway IH, Gearing AJH. Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 1992; 187: 584-9.
43 Giavazzi R, Chirivi RG, Garofalo A, Rambaldi A, Hemingway I, Pigott R, Gearing AJ. Soluble intercellular adhesion molecule 1 is released by human melanoma cells and is associated with tumor growth in nude mice. Cancer Res 1992; 52: 2628-30.
44 Rothlein R, Mainolfi EA, Czajkowki M, Martin SD. A form of circulating ICAM-1 in human serum. J Immunol 1991; 147: 3788-93.
45 Wellicome SM, Kapahi P, Mason JC, Lebranchu Y, Yarwood H, Haskard DO. Detection of a circulating form of vascular adhesion molecule 1: raised levels in rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Immunol 1993; 92: 412-8.
46 Borland G, Murphy G, Ager A. Tissue inhibitor of metalloproteinases-3 inhibits shedding of L-selectin from leukocytes. J Biol Chem 1999; 274: 2810-5.
47 Herren B, Raines EW, Ross R. Expression of a disintegrin-like protein in cultured human vascular cells and in vivo. FASEB J 1997; 11: 173-80.
48 Sadler JE. Thrombomodulin structure and function. Thromb Haemost 1997; 78: 392-5.
49 Ishii H, Majerus PW. Thrombomodulin is present in human plasma and urine. J Clin Invest 1985; 76: 2178-81.
50 Salomaa V, Matei C, Aleksic N, Sansores-Garcia L, Folsom AR, Juneja H, Chambless LE, Wu KK. 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. Lancet 1999; 353: 1729-34.
51 Peter K, Nawroth P, Conradt C, Nordt T, Weiss T, Boehme M, Wunsch A, Allenberg J, KYbler W, Bode C. Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. Arterioscler Thromb Vasc Biol 1997; 17: 505-12.
52 Blann AD, Dobrotova M, Kubisz P, McCollum CN. Von Willebrand Factor, soluble P-selectin, tissue plasminogen activator and plasminogen activator inhibitor in atherosclerosis. Thromb Haemost 1995; 74: 626-30.
53 Blann AD, Miller JP, McCollum CN. Von Willebrand Factor and soluble E-selectin in the prediction of cardiovascular disease progression in hyperlipidaemia. Atherosclerosis 1997; 132: 151-6.
54 DeCaterina R, Basta G, Lazzerini G, Dell'Omo G, Petrucci R, Morale M, Carmassi F, Pedrinelli R. Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17: 2646-54.
55 Otsuki M, Hashimoto K, Morimoto Y, Kishimoto T, Kasayama S. Circulating vascular cell adhesion molecule-1 (VCAM-1) in atherosclerotic NIDDM patients. Diabetes 1997; 46: 2096-101.
56 Mason JC, Kapahi P, Haskard DO. Detection of increased levels of circulating intercellular adhesion molecule 1 in some patients with rheumatoid arthritis but not in patients with systemic lupus erythematosus. Lack correlation with levels of circulating vascular adhesion molecule 1. Arthritis Rheum 1993; 36: 519-27.
57 Janssen BA, Luqmani RA, Gordon C, Hemingway IH, Bacon PA, Gearing AJ, Emery P. Correlation of blood levels of soluble adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis. Br J Rheumatol 1994; 33: 1112-6.
58 Banks RE, Gearing AJH, Hemingway DR, Norfolk DR, Perren TJ, Selby PJ. Circulating intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in human malignancies. Br J Cancer 1993; 68: 122-4.
59 Ghaisas NK, Shahi CN, Foley B, Goggins M, Crean P, Kelly A, Kelleher D, Walsh M. Elevated levels of circulating soluble adhesion molecules in peripheral blood of patients with unstable angina. Am J Cardiol 1997; 80: 617-9.
60 Mulvihill N, Foley JB, Ghaisas N, Murphy R, Crean P, Walsh M. Early temporal expression of soluble cellular adhesion molecules in patients with unstable angina and subendocardial myocardial infarction. Am J Cardiol 1999; 83: 1265-7.