The Role of CD39 in Cardiovascular Disease.

[摘要] While ATP and ADP are traditionally thought of as energy intermediaries in theintracellular space, these nucleotides primarily act as signaling molecules in the extracellularspace. By engaging purine receptors on the surface of leukocytes and endothelium in thevasculature, ATP and ADP can elicit inflammatory and pro-thrombotic responses. CD39, anecto-enzyme, rapidly metabolizes extracellular nucleotides to suppress purinergic signalingcascades. Though it is well established that CD39 regulates ADP-driven thrombosis, itremained unclear whether CD39 participates in ATP/ADP driven inflammation. This led tothe hypothesis that CD39 is a critical regulator of inflammation through the catabolism ofextracellular nucleotides. Studies of macrophage and neutrophil flux into post-ischemicbrain tissue and of atherosclerotic plaque development revealed a novel role for CD39 in theregulation of leukocyte activation. Leukocyte surface CD39 degrades ATP that wouldotherwise activate the P2X7 receptor, leading to a suppression of both the adhesion molecule-x-

[发布机构] University of Michigan

[效力级别] Vascular Physiology

[关键词] Ecto-enzyme;Vascular Physiology;Physiology;Health Sciences;Molecular and Integrative Physiology