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ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow
M C Bourdillon1, R N Poston, C Covacho
1INSERM U331/Faculté de Médecine RTH Laënnec, Lyon, France. bourdillon@lyon151.inserm.fr
Abstract:
Intercellular adhesion molecule (ICAM)-1, a major adhesion molecule, plays a critical role in the homing of leukocytes to sites of atherosclerotic lesions. 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 background) 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 weeks. A 3-fold reduction in lesion size was observed at all time points in DKO mice fed a chow diet. However, in DKO mice fed a fat diet, a marked reduction in the aortic lesion was observed at 3 and 15 weeks, which did not reach 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 weeks 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 deficiency. These studies show that ICAM-1 is implicated in the formation and progression of atherosclerotic lesions.
Insights
Intercellular adhesion molecule (ICAM)-1 deficiency significantly reduces early atherosclerotic lesion development in ApoE(-/-) mice. However, this protective effect diminishes over time, especially on a high-fat diet.
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- Intercellular adhesion molecule (ICAM)-1 is crucial for leukocyte homing to atherosclerotic lesions.
- The specific role of ICAM-1 in initiating and progressing vascular lesions in ApoE(-/-) mice remains largely uncharacterized.
Purpose of the Study:
- To investigate the impact of ICAM-1 deficiency on the development of aortic lesions in ApoE(-/-) mice under chow and high-fat diet conditions.
- To determine the temporal effects of combined ApoE and ICAM-1 knockout on atherosclerosis progression.
Main Methods:
- Atherosclerosis was studied in single knockout (ApoE(-/-)) and double knockout (ApoE(-/-), ICAM-1(-/-)) mice on a C57BL6 background.
- Mice were fed either a standard chow or a high-fat diet for 3, 6, 15, and 20 weeks.
- Aortic lesion size and plasma cholesterol levels were quantified.
Main Results:
- Double knockout mice showed a 3-fold reduction in aortic lesion size on a chow diet at all time points.
- On a high-fat diet, double knockout mice exhibited reduced lesion size at 3 and 15 weeks, but not significantly at 6 or 20 weeks.
- ICAM-1 deficiency provided protection against significant lesion development up to 6 weeks, after which lesion progression mirrored that of single knockout mice.
Conclusions:
- ICAM-1 plays a significant role in both the formation and progression of atherosclerotic lesions.
- The protective effect of ICAM-1 deficiency is time-dependent and diet-sensitive, particularly diminishing on a high-fat diet.
- Plasma cholesterol levels were not affected by ICAM-1 deficiency, suggesting a mechanism independent of systemic hyperlipidemia.
