© 1999 American Heart Association, Inc.
Original Contribution |
Patterns of Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Expression in Rabbit and Mouse Atherosclerotic Lesions and at Sites Predisposed to Lesion Formation
From the Department of Laboratory Medicine and Pathobiology (K.I., L.H., M.I., M.I.C.), University of Toronto and Toronto General Hospital Research Institute, Ontario, Canada, and Vascular Research Division, Department of Pathology (H.L., M.D., B.D.M.), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Myron I. Cybulsky, MD, Department of Laboratory Medicine and Pathobiology, Toronto General Hospital, 200 Elizabeth St, CCRW 1-855, Toronto, Ontario M5G 2C4, Canada. E-mail myron.cybulsky{at}utoronto.ca
Abstract—The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Inducible endothelial cell adhesion molecules may participate in this process. In aortas of normal chow-fed wild-type mice and rabbits, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), but not E-selectin, were expressed by endothelial cells in regions predisposed to atherosclerotic lesion formation. En face confocal microscopy of the mouse ascending aorta and proximal arch demonstrated that VCAM-1 expression was increased on the endothelial cell surface in lesion-prone areas. ICAM-1 expression extended into areas protected from lesion formation. Hypercholesterolemia induced atherosclerotic lesion formation in rabbits, LDL receptor and apolipoprotein E knockout mice, and Northern blot analysis demonstrated increased steady-state mRNA levels of VCAM-1 and ICAM-1, but not of E-selectin. Immunohistochemical staining revealed that VCAM-1 and ICAM-1 were expressed predominantly by endothelium in early lesions and by intimal cells in more advanced lesions. In early and advanced lesions, staining was most intense in endothelial cells at and adjacent to lesion borders. ICAM-1 staining extended into the uninvolved aorta. These expression patterns were highly reproducible in both species. The only difference was that VCAM-1 expression in endothelium over the central portions of lesions was found frequently in rabbits and rarely in mice. The expression of VCAM-1 by arterial endothelium in normal animals may represent a pathogenic mechanism or a phenotypic marker of predisposition to atherogenesis.
Key Words: atherosclerosis • endothelium • vascular cell adhesion molecule-1 • intercellular adhesion molecule-1 • expression pattern
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 A. K. Death, K. C. Y. McGrath, M. A. Sader, S. Nakhla, W. Jessup, D. J. Handelsman, and D. S. Celermajer Dihydrotestosterone Promotes Vascular Cell Adhesion Molecule-1 Expression in Male Human Endothelial Cells via a Nuclear Factor-{kappa}B-Dependent Pathway Endocrinology, April 1, 2004; 145(4): 1889 - 1897. [Abstract] [Full Text] [PDF]
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C. Kunsch, J. Luchoomun, J. Y. Grey, L. K. Olliff, L. B. Saint, R. F. Arrendale, M. A. Wasserman, U. Saxena, and R. M. Medford Selective Inhibition of Endothelial and Monocyte Redox-Sensitive Genes by AGI-1067: A Novel Antioxidant and Anti-Inflammatory Agent J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 820 - 829. [Abstract] [Full Text] [PDF]
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A. G. Passerini, D. C. Polacek, C. Shi, N. M. Francesco, E. Manduchi, G. R. Grant, W. F. Pritchard, S. Powell, G. Y. Chang, C. J. Stoeckert Jr., et al. Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta PNAS, February 24, 2004; 101(8): 2482 - 2487. [Abstract] [Full Text] [PDF]
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R. M. Porat, M. Grunewald, A. Globerman, A. Itin, G. Barshtein, L. Alhonen, K. Alitalo, and E. Keshet Specific Induction of tie1 Promoter by Disturbed Flow in Atherosclerosis-Prone Vascular Niches and Flow-Obstructing Pathologies Circ. Res., February 20, 2004; 94(3): 394 - 401. [Abstract] [Full Text] [PDF]
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S. Kaul and J. R. Lindner Visualizing coronary atherosclerosis in vivo: thinking big, imaging small J. Am. Coll. Cardiol., February 4, 2004; 43(3): 461 - 463. [Full Text] [PDF]
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R. Kiefmann, K. Heckel, M. Dorger, S. Schenkat, M. Stoeckelhuber, J. Wesierska-Gadek, and A. E. Goetz Role of poly(ADP-ribose) synthetase in pulmonary leukocyte recruitment Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L996 - L1005. [Abstract] [Full Text] [PDF]
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 A.-L. Yang, C. J. Jen, and H.-i. Chen Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study J Appl Physiol, September 1, 2003; 95(3): 1194 - 1200. [Abstract] [Full Text] [PDF]
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S.-P. Yang, L.-J. Ho, Y.-L. Lin, S.-M. Cheng, T.-P. Tsao, D.-M. Chang, Y.-L. Hsu, C.-Y. Shih, T.-Y. Juan, and J.-H. Lai Carvedilol, a new antioxidative {beta}-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-{kappa}B activity Cardiovasc Res, September 1, 2003; 59(3): 776 - 787. [Abstract] [Full Text] [PDF]
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C. L. Sundell, P. K. Somers, C. Q. Meng, L. K. Hoong, K.-L. Suen, R. R. Hill, L. K. Landers, A. Chapman, D. Butteiger, M. Jones, et al. AGI-1067: A Multifunctional Phenolic Antioxidant, Lipid Modulator, Anti-Inflammatory and Antiatherosclerotic Agent J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1116 - 1123. [Abstract] [Full Text] [PDF]
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A. Tailor and D. N. Granger Hypercholesterolemia Promotes P-Selectin-Dependent Platelet-Endothelial Cell Adhesion in Postcapillary Venules Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 675 - 680. [Abstract] [Full Text] [PDF]
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J. Guo, M. Van Eck, J. Twisk, N. Maeda, G. M. Benson, P. H.E. Groot, and T. J.C. Van Berkel Transplantation of Monocyte CC-Chemokine Receptor 2-Deficient Bone Marrow Into ApoE3-Leiden Mice Inhibits Atherogenesis Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 447 - 453. [Abstract] [Full Text] [PDF]
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F. de Nigris, L. O. Lerman, S. W. Ignarro, G. Sica, A. Lerman, W. Palinski, L. J. Ignarro, and C. Napoli From the Cover: Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress PNAS, February 4, 2003; 100(3): 1420 - 1425. [Abstract] [Full Text] [PDF]
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 G. D. Angelini, C. Lloyd, R. Bush, J. Johnson, and A. C. Newby An external, oversized, porous polyester stent reduces vein graft neointima formation, cholesterol concentration, and vascular cell adhesion molecule 1 expression in cholesterol-fed pigs J. Thorac. Cardiovasc. Surg., November 1, 2002; 124(5): 950 - 956. [Abstract] [Full Text] [PDF]
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A. D. Pradhan, N. Rifai, and P. M. Ridker Soluble Intercellular Adhesion Molecule-1, Soluble Vascular Adhesion Molecule-1, and the Development of Symptomatic Peripheral Arterial Disease in Men Circulation, August 13, 2002; 106(7): 820 - 825. [Abstract] [Full Text] [PDF]
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I. Baranova, T. Vishnyakova, A. Bocharov, Z. Chen, A. T. Remaley, J. Stonik, T. L. Eggerman, and A. P. Patterson Lipopolysaccharide Down Regulates Both Scavenger Receptor B1 and ATP Binding Cassette Transporter A1 in RAW Cells Infect. Immun., June 1, 2002; 70(6): 2995 - 3003. [Abstract] [Full Text] [PDF]
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S. M. Lessner, H. L. Prado, E. K. Waller, and Z. S. Galis Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model Am. J. Pathol., June 1, 2002; 160(6): 2145 - 2155. [Abstract] [Full Text] [PDF]
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 A. R. Brooks, P. I. Lelkes, and G. M. Rubanyi Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow Physiol Genomics, April 10, 2002; 9(1): 27 - 41. [Abstract] [Full Text] [PDF]
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M. E. Rosenfeld Leukocyte Recruitment Into Developing Atherosclerotic Lesions: The Complex Interaction Between Multiple Molecules Keeps Getting More Complex Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 361 - 363. [Full Text] [PDF]
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H. M. Dansky, C. B. Barlow, C. Lominska, J. L. Sikes, C. Kao, J. Weinsaft, M. I. Cybulsky, and J. D. Smith Adhesion of Monocytes to Arterial Endothelium and Initiation of Atherosclerosis Are Critically Dependent on Vascular Cell Adhesion Molecule-1 Gene Dosage Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1662 - 1667. [Abstract] [Full Text] [PDF]
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E. E. ERIKSSON, X. XIE, J. WERR, P. THOREN, and L. LINDBOM Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins FASEB J, May 1, 2001; 15(7): 1149 - 1157. [Abstract] [Full Text] [PDF]
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K. Y. Stokes, E. C. Clanton, J. M. Russell, C. R. Ross, and D. N. Granger NAD(P)H Oxidase-Derived Superoxide Mediates Hypercholesterolemia-Induced Leukocyte-Endothelial Cell Adhesion Circ. Res., March 16, 2001; 88(5): 499 - 505. [Abstract] [Full Text] [PDF]
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J. H. von der Thusen, T. J.C. van Berkel, and E. A.L. Biessen Induction of Rapid Atherogenesis by Perivascular Carotid Collar Placement in Apolipoprotein E-Deficient and Low-Density Lipoprotein Receptor-Deficient Mice Circulation, February 27, 2001; 103(8): 1164 - 1170. [Abstract] [Full Text] [PDF]
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G. W. Cockerill, T. Y. Huehns, A. Weerasinghe, C. Stocker, P. G. Lerch, N. E. Miller, and D. O. Haskard Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1-Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation Circulation, January 2, 2001; 103(1): 108 - 112. [Abstract] [Full Text] [PDF]
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