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Purinergic Dysfunction in Pulmonary Arterial Hypertension.

  • Cai, Zongye1
  • Tu, Ly2, 3
  • Guignabert, Christophe2, 3
  • Merkus, Daphne1, 4, 5
  • Zhou, Zhichao6
  • 1 Division of Experimental Cardiology Department of Cardiology Erasmus MCUniversity Medical Center Rotterdam Rotterdam the Netherlands. , (Netherlands)
  • 2 INSERM UMR_S 999Hôpital Marie Lannelongue Le Plessis-Robinson France. , (France)
  • 3 School of Medicine Université Paris-Saclay Kremlin-Bicêtre France. , (France)
  • 4 Walter Brendel Center of Experimental Medicine LMU Munich Munich Germany. , (Germany)
  • 5 German Center for Cardiovascular Research, Partner Site MunichMunich Heart Alliance Munich Germany. , (Germany)
  • 6 Division of Cardiology Department of Medicine Karolinska University HospitalKarolinska Institutet Stockholm Sweden. , (Sweden)
Published Article
Journal of the American Heart Association
Ovid Technologies Wolters Kluwer -American Heart Association
Publication Date
Sep 01, 2020
DOI: 10.1161/JAHA.120.017404
PMID: 32867554


Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance, which result in an increase in afterload imposed onto the right ventricle, leading to right heart failure. Current therapies are incapable of reversing the disease progression. Thus, the identification of novel and potential therapeutic targets is urgently needed. An alteration of nucleotide- and nucleoside-activated purinergic signaling has been proposed as a potential contributor in the pathogenesis of PAH. Adenosine-mediated purinergic 1 receptor activation, particularly A2AR activation, reduces pulmonary vascular resistance and attenuates pulmonary vascular remodeling and right ventricle hypertrophy, thereby exerting a protective effect. Conversely, A2BR activation induces pulmonary vascular remodeling, and is therefore deleterious. ATP-mediated P2X7R activation and ADP-mediated activation of P2Y1R and P2Y12R play a role in pulmonary vascular tone, vascular remodeling, and inflammation in PAH. Recent studies have revealed a role of ectonucleotidase nucleoside triphosphate diphosphohydrolase, that degrades ATP/ADP, in regulation of pulmonary vascular remodeling. Interestingly, existing evidence that adenosine activates erythrocyte A2BR signaling, counteracting hypoxia-induced pulmonary injury, and that ATP release is impaired in erythrocyte in PAH implies erythrocyte dysfunction as an important trigger to affect purinergic signaling for pathogenesis of PAH. The present review focuses on current knowledge on alteration of nucleot(s)ide-mediated purinergic signaling as a potential disease mechanism underlying the development of PAH.

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