Arteriosclerosis and Thrombosis, Vol 13, 197-204, Copyright © 1993 by American Heart Association

ARTICLES

An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium

H Li, MI Cybulsky, MA Gimbrone Jr and P Libby
Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, Boston, MA 02115.

Accumulation of monocyte-derived foam cells in focal areas of the arterial intima is a key step in early atherogenesis. We investigated the expression of vascular cell adhesion molecule-1 (VCAM-1), a mononuclear leukocyte adhesion molecule, in the arterial endothelium during the early phases of diet-induced atherogenesis in rabbits in vivo and the regulation of VCAM-1 expression by cytokines in rabbit aortic organoid cultures in vitro. Rabbits were fed either an atherogenic diet (containing 0.3% cholesterol, 9% coconut oil, and 1% corn oil) or an isocaloric control diet (10% corn oil) for 4 days or 1, 3, 6, or 13 weeks. The endothelium in the ascending aorta focally expressed VCAM-1 after only 1 week on the atherogenic diet but before the first appearance of intimal macrophages, as judged by immunohistochemical staining of serial sections. The rabbits that consumed the atherogenic diet for 3 weeks or longer developed lesions in the intima composed of macrophages bearing class II major histocompatibility antigen (MHC-II). Endothelial cells continued to focally express VCAM-1 at sites of MHC-II-positive intimal macrophages for up to 13 weeks. The ascending aortas of control rabbits lacked VCAM- 1 or MHC-II-positive endothelium or macrophages at all times studied. These observations demonstrate the focal activation of arterial endothelium as early as 7 days after initiation of an atherogenic diet (at serum cholesterol levels of 308 +/- 57 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

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				N. Marx, G. K. Sukhova, T. Collins, P. Libby, and J. Plutzky PPAR{alpha} Activators Inhibit Cytokine-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells Circulation, June 22, 1999; 99(24): 3125 - 3131. [Abstract] [Full Text] [PDF]

				H. Qian, V. Neplioueva, G. A. Shetty, K. M. Channon, and S. E. George Nitric Oxide Synthase Gene Therapy Rapidly Reduces Adhesion Molecule Expression and Inflammatory Cell Infiltration in Carotid Arteries of Cholesterol-Fed Rabbits Circulation, June 15, 1999; 99(23): 2979 - 2982. [Abstract] [Full Text] [PDF]

				C. L. Ramos, Y. Huo, U. Jung, S. Ghosh, D. R. Manka, I. J. Sarembock, and K. Ley Direct Demonstration of P-Selectin– and VCAM-1–Dependent Mononuclear Cell Rolling in Early Atherosclerotic Lesions of Apolipoprotein E–Deficient Mice Circ. Res., June 11, 1999; 84(11): 1237 - 1244. [Abstract] [Full Text] [PDF]

				M. M. Tarpey, C. R. White, E. Suarez, G. Richardson, R. Radi, and B. A. Freeman Chemiluminescent Detection of Oxidants in Vascular Tissue : Lucigenin But Not Coelenterazine Enhances Superoxide Formation Circ. Res., May 28, 1999; 84(10): 1203 - 1211. [Abstract] [Full Text] [PDF]

				J. A. McCrohon, W. Jessup, D. J. Handelsman, and D. S. Celermajer Androgen Exposure Increases Human Monocyte Adhesion to Vascular Endothelium and Endothelial Cell Expression of Vascular Cell Adhesion Molecule-1 Circulation, May 4, 1999; 99(17): 2317 - 2322. [Abstract] [Full Text] [PDF]

				S. Merat, F. Casanada, M. Sutphin, W. Palinski, and P. D. Reaven Western-Type Diets Induce Insulin Resistance and Hyperinsulinemia in LDL Receptor-Deficient Mice But Do Not Increase Aortic Atherosclerosis Compared With Normoinsulinemic Mice in Which Similar Plasma Cholesterol Levels Are Achieved by a Fructose-Rich Diet Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1223 - 1230. [Abstract] [Full Text] [PDF]

				T.-S. Lee, H.-C. Yen, C.-C. Pan, and L.-Y. Chau The Role of Interleukin 12 in the Development of Atherosclerosis in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 734 - 742. [Abstract] [Full Text] [PDF]

				P. T. Shih, M.-L. Brennan, D. K. Vora, M. C. Territo, D. Strahl, M. J. Elices, A. J. Lusis, and J. A. Berliner Blocking Very Late Antigen-4 Integrin Decreases Leukocyte Entry and Fatty Streak Formation in Mice Fed an Atherogenic Diet Circ. Res., February 19, 1999; 84(3): 345 - 351. [Abstract] [Full Text] [PDF]

				P. W. Baker, K.-A. Rye, J. R. Gamble, M. A. Vadas, and P. J. Barter Ability of reconstituted high density lipoproteins to inhibit cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells J. Lipid Res., February 1, 1999; 40(2): 345 - 353. [Abstract] [Full Text]

				G. A. Truskey, R. A. Herrmann, J. Kait, and K. M. Barber Focal Increases in Vascular Cell Adhesion Molecule-1 and Intimal Macrophages at Atherosclerosis-Susceptible Sites in the Rabbit Aorta After Short-Term Cholesterol Feeding Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 393 - 401. [Abstract] [Full Text] [PDF]

				P. Holm, H. L. Andersen, G. Arroe, and S. Stender Gender Gap in Aortic Cholesterol Accumulation in Cholesterol-Clamped Rabbits : Role of the Endothelium and Mononuclear-Endothelial Cell Interaction Circulation, December 15, 1998; 98(24): 2731 - 2737. [Abstract] [Full Text] [PDF]

				K. N. Islam, S. Devaraj, and I. Jialal {alpha}-Tocopherol Enrichment of Monocytes Decreases Agonist-Induced Adhesion to Human Endothelial Cells Circulation, November 24, 1998; 98(21): 2255 - 2261. [Abstract] [Full Text] [PDF]

				L. E. Rohde, R. T. Lee, J. Rivero, M. Jamacochian, L. H. Arroyo, W. Briggs, N. Rifai, P. Libby, M. A. Creager, and P. M. Ridker Circulating Cell Adhesion Molecules Are Correlated With Ultrasound-Based Assessment of Carotid Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1765 - 1770. [Abstract] [Full Text] [PDF]

				P. Libby The interface of atherosclerosis and thrombosis: basic mechanisms Vascular Medicine, August 1, 1998; 3(3): 225 - 229. [Abstract] [PDF]

				R. Scalia, J. Z. Appel III, and A. M. Lefer Leukocyte-Endothelium Interaction During the Early Stages of Hypercholesterolemia in the Rabbit : Role of P-Selectin, ICAM-1, and VCAM-1 Arterioscler Thromb Vasc Biol, July 1, 1998; 18(7): 1093 - 1100. [Abstract] [Full Text] [PDF]