CD73/Ecto-5′-Nucleotidase Protects Against Vascular Inflammation and Neointima Formation

Abstract

Background— 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. Methods and Results— 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)-κB 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 α4β1 integrin. After wire injury of carotid arteries, CD73 expression and activity were upregulated in wild-type mice, whereas neoint...