Mc. Bourdillon et al., ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet, ART THROM V, 20(12), 2000, pp. 2630-2635
Intercellular adhesion molecule (ICAM)-1, a major adhesion molecule, plays
a critical role in the homing of leukocytes to sites of atherosclerotic les
ions. However, very little is known on the role of ICAM-1 in initiating and
perpetuating vascular lesions in ApoE(-/-) mice fed a chow or a fat diet.
This study has investigated the mean aortic lesions in mice (C57BL6 backgro
und) with a single-knockout (ApoE(-/-)) or double-knockout (DKO; ApoE(-/-),
ICAM-1(-/-)) fed a chow or a fat diet over a period of 3, 6, 15, and 20 we
eks. A 3-fold reduction in lesion size was observed at all time points in D
KO mice fed a chow diet. However, in DKO mice fed a fat diet, a marked redu
ction in the aortic lesion was observed at 3 and 15 weeks, which did not re
ach a significant level at 6 and 20 weeks. This study shows in essence that
DKO mice are protected from developing significant lesions for up to 6 wee
ks when fed a chow diet and from 3 to 6 weeks when fed a fat diet. After 6
weeks, the lesion size of the DKO mice follows that of the single-knockout
mice when fed a chow diet and gets to the same level in mice fed a fat diet
. Plasma cholesterol levels were not altered as a result of ICAM-1 deficien
cy. These studies show that ICAM-1 is implicated in the formation and progr
ession of atherosclerotic lesions.