CD73/ecto-5'-nucleotidase protects against vascular inflammation and neointima formation

Circulation
Alma ZerneckeChristian Weber

Abstract

Although CD73/ecto-5'-nucleotidase has been implicated in maintaining vasoprotection, its role in regulating endothelial adhesion molecule or inflammatory monocyte recruitment (eg, in the context of vascular injury) remains to be defined. Compared with wild-type mice, CD73-deficient (CD73(-/-)) mice exhibit increased luminal staining and protein and transcript expression for vascular cell adhesion molecule (VCAM)-1 in carotid arteries. In vitro, aortic endothelial cells (ECs) from CD73(-/-) mice display an upregulation of mRNA and protein expression of VCAM-1, associated with increased nuclear factor (NF)-kappaB activity, as determined by chromatin cross-linking and immunoprecipitation or quantitative p65 binding assays. CD73(-/-) ECs and carotid arteries perfused ex vivo supported increased monocyte arrest under flow conditions, which was mediated by alpha(4beta1) integrin. After wire injury of carotid arteries, CD73 expression and activity were upregulated in wild-type mice, whereas neointimal plaque formation and macrophage content were increased in CD73(-/-) mice versus wild-type mice, concomitant with elevated NF-kappaB activation, luminal VCAM-1 expression, and soluble VCAM-1 concentrations. In contrast, reconstitution of...Continue Reading

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