CD39 in the development and progression of pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a devastating progressive disease characterised by pulmonary arterial vasoconstriction and vascular remodelling. Endothelial dysfunction has emerged as a contributing factor in the development of PAH. However, despite progress in the understanding of the pathophysiology of this disease, current therapies fail to impact upon long-term outcomes which remain poor in most patients. Recent observations have suggested the disturbances in the balance between ATP and adenosine may be integral to the vascular remodelling seen in PAH. CD39 is an enzyme important in regulating these nucleos(t)ides which may also provide a novel pathway to target for future therapies. This review summarises the role of adenosine signalling in the development and progression of PAH and highlights the therapeutic potential of CD39 for treatment of PAH.

CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta

“…Hence, CD39 on the surface of placental villi [accounting for approximately 10 m 2 at term ( Biswas et al, 2008 )] may be considered to fulfill similar functions as described for the vascular endothelium. As the rate-limiting enzyme in ectonucleotidase-mediated ATP to adenosine conversion, CD39 is the molecular break in regulating extracellular ATP, which functions as a danger signal (DAMP), triggering activation of P2 receptors and downstream pro-inflammatory responses ( Kanthi et al, 2014 ; Zhao et al, 2017 ; Willcox et al, 2022 ). The CD39/CD73 hydrolytic activity on the purinergic cascade is an important immunoregulatory effector, by the breakdown of ATP into the anti-inflammatory molecules ADP and AMP and finally into adenosine ( da Silva et al, 2022 ).…”