title: Changes of peripheral A2A adenosine receptors in chronic heart failure and cardiac transplantation.
abstract: Peripheral blood mononuclear cells of chronic heart failure (CHF) patients produce great amounts of pro-inflammatory cytokines, indicating that circulating cells are activated and could mirror changes occurring in inflammatory cells infiltrating the failing heart. Adenosine is a regulatory metabolite acting through four membrane receptors that are linked to adenylyl cyclase: activation of the A2A receptor subtype has been reported to inhibit cytokine release. Changes of the adenosinergic system may play a role in CHF development. Here we report an increase of A2A receptor expression, density, and coupling to adenylyl cyclase in blood circulating cells of CHF patients. A2A receptor up-regulation was also found in the explanted hearts of these patients, suggesting that changes of peripheral adenosine receptors mirror changes occurring in the disease target organ. In a cohort of patients followed longitudinally after heart transplantation, alterations of peripheral A2A adenosine receptor progressively normalized to control values within 6 months, suggesting that improvement of cardiac performance is accompanied by progressive restoration of a normal adenosinergic system. These results validate the importance of the A2A receptor in human diseases characterized by a marked inflammatory/immune component and suggest that the evaluation of this receptor in peripheral blood cells may be useful for monitoring hemodynamic changes and the efficacy of pharmacological and non-pharmacological treatments in CHF patients.
authors.affiliation: Department of Clinical and Experimental Medicine, Institute of Pharmacology and Interdisciplinary Centre for the Study of Inflammation, University of Ferrara, Ferrara, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Camurri
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Maccherini
authors.forename: Francesco
authors.initials: F
authors.lastname: Diciolla
authors.forename: Linda
authors.initials: L
authors.lastname: Ceccatelli
authors.forename: Pietro Enea
authors.initials: PE
authors.lastname: Lazzerini
authors.forename: Canan
authors.initials: C
authors.lastname: Ulouglu
authors.forename: Flaminio
authors.initials: F
authors.lastname: Cattabeni
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Maria P
authors.initials: MP
authors.lastname: Abbracchio
mesh_terms: D001667:Binding, Competitive; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000097:blood* / Q000378:metabolism; D014227:Triazines / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D014316:Tritium
chemical_list: D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D014316:Tritium