CD39: Interface between vascular thrombosis and inflammation

Abstract

Extracellular nucleotides play a critical role in vascular thrombosis and inflammation. Alterations in purinergic extracellular nucleotide concentrations activate pathways that result in platelet degranulation and aggregation, and endothelial and leukocyte activation and recruitment. CD39, the dominant vascular nucleotidase, hydrolyzes ATP and ADP to provide the substrate for generation of the anti-inflammatory and antithrombotic mediator adenosine. The purinergic signaling system, with CD39 at its center, plays an important role in modulating vascular homeostasis and the response to vascular injury, as seen in clinically relevant diseases such as stroke, ischemia-reperfusion injury, and pulmonary hypertension. A growing body of knowledge of the purinergic signaling pathway implicates CD39 as a critical modulator of vascular thrombosis and inflammation. Therapeutic strategies targeting CD39 offer promising opportunities in the management of vascular thromboinflammatory diseases.

Figure 1.

The CD39/CD73 pathway modulates vascular inflammation and thrombosis in response to injury. Nucleotides released during cell activation/injury bind to P2 receptors to activate thrombo-inflammatory programs in the vasculature by binding to receptors on the endothelium, platelets and leukocytes. Endothelial and circulating leukocytes express the catabolic machinery to convert ATP/ADP into adenosine to quench the pro-inflammatory and pro-thrombotic signals and exert a potent, protective vascular effect. Adenosine triphosphate (ATP); adenosine diphosphate (ADP); adenosine monophosphoate (ADP).