Abstract 16362: Adenosine Deaminase 2 Inhibits Adenosine-Driven Neutrophil Activation in Atherosclerosis

Introduction: In recent years, many studies have implicated activation of neutrophils in the process of atherosclerosis. Neutrophils can be activated by adenosine which is commonly found in atherosclerotic lesions. Adenosine Deaminase 2 (ADA2) converts adenosine into inosine and patients afflicted by loss-of-function mutations in ADA2 suffer from various vascular and inflammatory phenotypes related to disturbed neutrophil biology. We hypothesized that ADA2 plays a role in atherosclerosis development by regulating neutrophil activation. Methods and Results: Plasma levels of ADA2 in humans were negatively correlated with neutrophil activation as measured by circulating levels of myeloperoxidase (MPO). Immunohistochemical staining of human carotid arteries showed that ADA2 protein is present in human atherosclerotic lesions. Subsequent whole mount in situ hybridization indicated that ADA2 RNA is produced in atherosclerotic lesions. Mass spectrometry imaging was used to visualize the spatial distribution of a...