Details

Autor(en) / Beteiligte

• Nageh, M F
• Sandberg, E T
• Marotti, K R
• Lin, A H
• Melchior, E P
• Bullard, D C
• Beaudet, A L

Titel

Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice

Ist Teil von

• Arteriosclerosis, thrombosis, and vascular biology, 1997-08, Vol.17 (8), p.1517-1520

Ort / Verlag

United States

Erscheinungsjahr

1997

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 beta 2-(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.