Changes of peripheral A2A adenosine receptors in chronic heart failure and cardiac transplantation.
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.
Varani
Katia
K
Department of Clinical and Experimental Medicine, Institute of Pharmacology and Interdisciplinary Centre for the Study of Inflammation, University of Ferrara, Ferrara, Italy.
Laghi-Pasini
Franco
F
Camurri
Alessandra
A
Capecchi
Pier Leopoldo
PL
Maccherini
Massimo
M
Diciolla
Francesco
F
Ceccatelli
Linda
L
Lazzerini
Pietro Enea
PE
Ulouglu
Canan
C
Cattabeni
Flaminio
F
Borea
Pier Andrea
PA
Abbracchio
Maria P
MP
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
D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D014316:Tritium