Abstract 12528: Intima Thickening, Adenosine Reduction and Calcification in CD73-Deficient Mice

Abstract

Introduction and Hypothesis: The 5' exonucleotidase, CD73, is a key enzyme for extracellular adenosine production. Mutations of the CD73 gene NT5E have been recently reported to cause a rare arterial disease named Arterial Calcification due to Deficiency of CD73 (ACDC). Using a murine model of ACDC, we tested the hypothesis that CD73 protects the arterial wall from hyperplasia and inhibits calcification of vascular smooth muscle cells (SMC). Methods and Results: Echocardiography showed that CD73 deficient mice ( CD73 -/- , n=11) (1.5 yr old, both sexes) had significantly increased aortic intima thickness than C57BL/6J wild type mice (WT, n=8). In culture with inorganic phosphate (Pi, 3.6mM) for 9 days CD73 -/- aortic SMC exhibited elevation of intracellular calcium contents than WT cells (Fig. 1a). HPLC analysis revealed more than 50% reduction of extracellular adenosine in CD73 -/- SMC compared to that in WT SMC (Fig. 1b). Addition of recombinant apolipoprotein-J (Apo-J, 6μg/mL) diminished Pi-induced calcification and restored extracellular adenosine levels in both CD73 -/- - and WT SMC. Conclusions: CD73 plays a key role in maintaining arterial intimal normality, adenosine production and de-calcification. Apo-J serves a regulator of vascular adenosine production and calcification in CD73 -/- mice.