Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1517-1520
© 1997 American Heart Association, Inc.
Articles |
Deficiency of Inflammatory Cell Adhesion Molecules Protects Against Atherosclerosis in Mice
From the Departments of Molecular and Human Genetics and Medicine, Baylor College of Medicine (M.F.N., E.T.S., D.C.B., A.L.B.), and the Howard Hughes Medical Institute (A.L.B.), Houston, Tex; and Molecular Biology Research, Pharmacia & Upjohn Inc, Kalamazoo, Mich (K.R.M., A.H.L., E.P.M.).
Correspondence to Arthur L. Beaudet, MD, Baylor College of Medicine, One Baylor Plaza, T619, Houston, TX 77030. E-mail abeaudet{at}bcm.tmc.edu
Abstract Leukocyte and endothelial cell adhesion molecules (CAMs) are essential for emigration of leukocytes, with the selectins mediating the initial step of leukocyte "rolling" and the ß2-(CD18) integrins and intercellular adhesion molecule-1 (ICAM-1) being important for firm adhesion and emigration. On the basis of evidence for an inflammatory component in the pathogenesis of atherosclerosis, including increased expression of CAMs, cytokines, and growth factors, we tested the hypothesis that decreased expression of inflammatory CAMs would reduce susceptibility to atherosclerosis. Using C57BL/6 mice fed a high-fat diet, we observed a 50% to 75% reduction in atherosclerotic fatty streaks in mice with homozygous mutations for ICAM-1, P-selectin, CD18, both ICAM-1 and CD18, or both ICAM-1 and P-selectin. In contrast to previous evidence of increased expression of CAMs in atherosclerotic lesions, which does not prove a cause-and-effect relationship, these data indicate directly that the level of expression of CAMs can determine the susceptibility to the formation of atherosclerotic fatty streaks. The results suggest that genetic variation at these loci could influence susceptibility to atherosclerosis and that pharmacological reduction of the expression or function of these CAMs might protect against atherosclerosis.
Key Words: atherosclerosis • selectins • intercellular adhesion molecule-1 • ß2-integrins • inflammation
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|
|
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|
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|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
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|
|
|
|
|
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|
|
|
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