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Reduced atherosclerotic lesion size in P-selectin deficient apolipoprotein E-knockout mice fed a chow but not a fat
Marie-Claude Bourdillon1, Jacques Randon, Lydie Barek
1EA-3740, INSERM-IFR62, Faculté de Médecine Laënnec, Université Claude Bernard Lyon 1, Lyon, France.
Abstract:
P-selectin. We investigated the role of P-selectin on the development of vascular lesions in an ApoE(-/-) male mice. Double-knockout (ApoE(-/-), P-selectin(-/-); DKO) were compared to single-knockout (ApoE(-/-); SKO) mice. They were fed a chow or fat diet for 3, 6, 15, and 20 weeks, without any differences in cholesterol levels. DKO mice fed a chow diet exhibited a ratio of lesion area over media lower than SKO mice, for 3 (P < .03) , 6 (P < .001), and 15 (P < .02) weeks. DKO mice fed a fat diet showed a lower ratio only at 3 weeks. P-selectin deficiency in ApoE(-/-) mice has a protective effect in atherosclerotic lesions development. Reduction of lesion size depends on diet type and duration. A fat diet could neutralize the beneficial effects of P-selectin deficiency, inducing atherosclerotic lesions via probably other adhesion molecules.
Insights
P-selectin deficiency reduces vascular lesions in ApoE(-/-) mice. However, a high-fat diet may counteract this protective effect, suggesting other molecules contribute to atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- P-selectin plays a role in inflammatory processes relevant to atherosclerosis.
- Apolipoprotein E knockout (ApoE(-/-)) mice are a standard model for studying atherosclerosis.
- Understanding the specific contribution of P-selectin is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of P-selectin in the development of vascular lesions in ApoE(-/-) mice.
- To compare the impact of P-selectin deficiency on atherosclerosis under different dietary conditions.
Main Methods:
- Comparison of double-knockout (ApoE(-/-), P-selectin(-/-); DKO) mice with single-knockout (ApoE(-/-); SKO) mice.
- Mice were fed either a standard chow diet or a high-fat diet for up to 20 weeks.
- Quantification of lesion area relative to media area to assess lesion progression.
Main Results:
- DKO mice on a chow diet showed significantly reduced lesion area/media ratio at 3, 6, and 15 weeks compared to SKO mice.
- DKO mice on a high-fat diet exhibited reduced lesion area/media ratio only at 3 weeks.
- No significant differences in cholesterol levels were observed between DKO and SKO mice.
Conclusions:
- P-selectin deficiency confers a protective effect against atherosclerotic lesion development in ApoE(-/-) mice.
- The reduction in lesion size is dependent on both diet type and duration of exposure.
- A high-fat diet may neutralize the benefits of P-selectin deficiency, potentially implicating other adhesion molecules in atherosclerosis progression.
