Deficiency of Inflammatory Cell Adhesion Molecules Protects Against Atherosclerosis in Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 17; no. 8; pp. 1517 - 1520
• Main Authors: Nageh, Maged F, Sandberg, Eric T, Marotti, Keith R, Lin, Alice H, Melchior, Earline P, Bullard, Daniel C, Beaudet, Arthur L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.08.1997; Hagerstown, MD Lippincott
• Subjects: Animal Feed; Animals; Arteriosclerosis - prevention & control; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; CD18 Antigens - genetics; Cholesterol, Dietary - administration & dosage; Dietary Fats - administration & dosage; Disease Susceptibility; Female; Gene Expression; Homozygote; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Intercellular Adhesion Molecule-1 - pharmacology; Leukocyte-Adhesion Deficiency Syndrome - physiopathology; Lipids - blood; Medical sciences; Mice; Mice, Inbred C57BL; Mutation; P-Selectin - genetics; Endothelial cell; Pathophysiology; Rodentia; Cardiovascular disease; Exploration; Venule; Adhesion; Vascular disease; Molecules; Vertebrata; Mammalia; Mouse; Animal; Atherosclerosis; Inflammatory cell
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.atv.17.8.1517

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 beta2-(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. (Arterioscler Thromb Vasc Biol. 1997;17:1517-1520.)