The Role of CD39 in Cardiovascular Disease.

Abstract

While ATP and ADP are traditionally thought of as energy intermediaries in the intracellular space, these nucleotides primarily act as signaling molecules in the extracellular space. By engaging purine receptors on the surface of leukocytes and endothelium in the vasculature, ATP and ADP can elicit inflammatory and pro-thrombotic responses. CD39, an ecto-enzyme, rapidly metabolizes extracellular nucleotides to suppress purinergic signaling cascades. Though it is well established that CD39 regulates ADP-driven thrombosis, it remained unclear whether CD39 participates in ATP/ADP driven inflammation. This led to the hypothesis that CD39 is a critical regulator of inflammation through the catabolism of extracellular nucleotides. Studies of macrophage and neutrophil flux into post-ischemic brain tissue and of atherosclerotic plaque development revealed a novel role for CD39 in the regulation of leukocyte activation. Leukocyte surface CD39 degrades ATP that would otherwise activate the P2X7 receptor, leading to a suppression of both the adhesion molecule -x-