CD73 Promotes Age-Dependent Accretion of Atherosclerosis

Autor: Nadia R. Sutton, David J. Pinsky, Matthew C. Hyman, Imran M. Rashid, Daniel R. Goldstein, Diane Bouis, Alexandra L. McCubbrey, Annie Mei, Kris M. Mann
Rok vydání: 2020
Předmět:
Zdroj: Arterioscler Thromb Vasc Biol
ISSN: 1524-4636
1079-5642
Popis: Objective: CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis. Approach and results: Mice doubly deficient in CD73 and ApoE (apolipoprotein E; ( cd73 − /− /apoE −/− ) were generated, and the extent of aortic atherosclerotic plaque was compared with apoE −/− controls at 12, 20, 32, and 52 weeks. By 12 weeks of age, cd73 −/− /apoE −/− mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in apoE −/− controls, P P P cd73 −/− /apoE −/− mice and apoE −/− controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels ( cd73 −/− /apoE −/− versus apoE −/− at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well], P Conclusions: At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.
Databáze: OpenAIRE