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Updated: Mar 2, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Complete deletion of Cd39 is atheroprotective in apolipoprotein E-deficient mice
Marco De Giorgi1, Keiichi Enjyoji1, Gordon Jiang1
1Transplant Institute and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Insights
Complete deletion of Cd39 surprisingly reduces atherosclerosis development in hyperlipidemic mice. This is linked to reduced platelet activation, higher HDL levels, and improved cholesterol efflux, highlighting complex purinergic signaling in vascular disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Metabolic Diseases
Background:
- Cd39 plays a role in purinergic signaling by breaking down extracellular ATP and ADP into adenosine.
- Adenosine possesses anti-inflammatory properties within the vasculature.
- The specific role of Cd39 in atherosclerosis development in hyperlipidemic conditions requires further elucidation.
Purpose of the Study:
- To investigate the role of Cd39 in the development of atherosclerosis in hyperlipidemic mouse models.
- To determine the impact of complete Cd39 deletion on atherosclerotic lesion formation and composition.
- To explore the underlying mechanisms contributing to any observed atheroprotective effects.
Main Methods:
- Utilized apolipoprotein E knockout (ApoE KO) and Cd39/ApoE double knockout (DKO) mice fed either a chow or Western diet for up to 20 weeks.
- Evaluated atherosclerotic lesion size and plaque composition, including foam cells and necrotic cores.
- Assessed platelet reactivity to ADP in vitro and platelet survival in vivo.
- Investigated cholesterol efflux in macrophages using genetic deletion or pharmacological inhibition of Cd39, focusing on ABCA1 and ApoA1.
Main Results:
- DKO mice exhibited significantly reduced atherosclerotic lesions compared to ApoE KO mice, regardless of diet.
- Plaque analysis in DKO mice revealed fewer foam cells and smaller necrotic cores.
- DKO mice displayed impaired platelet reactivity to ADP and prolonged platelet survival, indicating reduced in vivo platelet activation.
- Genetic or pharmacological Cd39 deletion in macrophages enhanced cholesterol efflux via ABCA1 to ApoA1, correlating with elevated plasma HDL levels in DKO mice.
Conclusions:
- Complete deletion of Cd39 paradoxically attenuates atherosclerosis development in hyperlipidemic mice.
- The atheroprotective phenotype in DKO mice is associated with diminished platelet activation, increased plasma HDL levels, and enhanced cholesterol efflux.
- These findings underscore the intricate role of purinergic signaling in the pathogenesis of atherosclerosis.
Abstract:
Cd39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of Cd39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE-/-) and Cd39/ApoE double KO (DKO) (Cd39-/-/ApoE-/-) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly fewer atherosclerotic lesions than ApoE KO mice, irrespective of diet. Analyses of plaque composition revealed diminished foam cells in the fatty streaks and smaller necrotic cores in advanced lesions of DKO mice, when compared with those in ApoE KO mice. This atheroprotective phenotype was associated with impaired platelet reactivity to ADP in vitro and prolonged platelet survival, suggesting decreased platelet activation in vivo. Further studies with either genetic deletion or pharmacological inhibition of Cd39 in macrophages revealed increased cholesterol efflux mediated via ABCA1 to ApoA1. This phenomenon was associated with elevated plasma HDL levels in DKO mice. Our findings indicate that complete deletion of Cd39 paradoxically attenuates development of atherosclerosis in hyperlipidemic mice. We propose that this phenotype occurs, at least in part, from diminished platelet activation, increased plasma HDL levels, and enhanced cholesterol efflux and indicates the complexity of purinergic signaling in atherosclerosis.
