Related Experiment Video
Updated: May 29, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Inactivation of CD73 promotes atherogenesis in apolipoprotein E-deficient mice
Anja Buchheiser1, Annette Ebner, Sandra Burghoff
1Department of Cardiovascular Physiology, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Aims:
CD73 (ecto-5'-nucleotidase) is expressed by a broad range of immune cells and attenuates inflammation in several acute disease models. This study therefore explored the role of CD73-derived adenosine in a model of chronic vascular inflammation such as atherogenesis.
Methods And Results:
CD73(-/-) mice were backcrossed into the apolipoprotein E (ApoE(-/-)) background. In CD73(-/-)/ApoE(-/-) double mutants, atherosclerotic lesion formation was increased by ∼50% compared with ApoE(-/-). However, the cellular composition and extracellular matrix of the plaques did not differ. Surprisingly, we found significant activity and expression of CD73 in the plaque of ApoE(-/-) mice which increased over time. CD73 co-localized with macrophages, Tregs, and cells of mesenchymal origin. Genome-wide microarray analysis of the aorta lacking CD73 revealed upregulation of endothelin-1 (Edn1) mRNA together with changes of genes in lipid metabolism and the Wnt and nuclear factor kappa B pathways. Measurement of plasma levels verified the upregulation of Edn1 in CD73(-/-) and double mutants. Plasma triglycerides (TG) were also found to be significantly elevated in the CD73(-/-)/ApoE(-/-) mice compared with ApoE(-/-) controls.
Conclusion:
Lack of CD73 promotes atherogenesis most likely by de-inhibition of resident macrophages and T cells. Elevated Edn1 and TG levels may have contributed. This establishes CD73-derived adenosine as a direct or indirect regulator of atherogenesis.
Insights
Lack of CD73 enzyme accelerates atherosclerosis development in mice. This is likely due to increased inflammation and elevated endothelin-1 and triglyceride levels, highlighting CD73
Area of Science:
- Immunology
- Cardiovascular Research
- Metabolic Disease
Background:
- CD73 (ecto-5'-nucleotidase) is an enzyme expressed on immune cells that reduces inflammation in acute conditions.
- Atherogenesis, a chronic vascular inflammation, is a key process in the development of cardiovascular disease.
- The role of CD73-derived adenosine in chronic vascular inflammation like atherogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the role of CD73 and its product adenosine in the development of atherosclerosis.
- To determine how CD73 deficiency impacts atherosclerotic lesion formation and associated molecular pathways.
Main Methods:
- Generated CD73(-/-)/ApoE(-/-) double mutant mice by backcrossing CD73 knockout mice onto an apolipoprotein E-deficient background.
- Analyzed atherosclerotic lesion formation, cellular composition, and extracellular matrix in the aorta of mutant and control mice.
- Performed genome-wide microarray analysis of aortas and measured plasma levels of endothelin-1 (Edn1) and triglycerides (TG).
Main Results:
- CD73(-/-)/ApoE(-/-) mice exhibited a ~50% increase in atherosclerotic lesion formation compared to ApoE(-/-) controls.
- Upregulation of endothelin-1 (Edn1) mRNA and altered gene expression in lipid metabolism, Wnt, and NF-κB pathways were observed in CD73-deficient aortas.
- Elevated plasma Edn1 and triglyceride levels were found in CD73(-/-)/ApoE(-/-) mice.
Conclusions:
- CD73 deficiency exacerbates atherogenesis, likely by promoting inflammation through de-inhibition of macrophages and T cells.
- Elevated Edn1 and TG levels may contribute to the pro-atherogenic effect of CD73 deficiency.
- CD73-derived adenosine is identified as a significant regulator, directly or indirectly, of the atherogenesis process.
