Transcriptomic profiling of the four adenosine receptors in human leukocytes of heart failure patients.

Adenosine is a potent extracellular messenger produced in high concentrations under metabolically unfavorable conditions. Adenosine restores tissue homeostasis through the interaction with its membrane receptors (A 1 R, A 2a R, A 2b R, A 3 R), acting as a retaliatory metabolite. The aim of this study was to evaluate the transcriptomic profiling of ARs in human leukocytes of HF patients as a function of clinical severity and the possible changes with respect to healthy subjects (C). Total RNA was extracted from leukocytes of C (n=8) and of HF patients (NYHA I-II n=9; NYHA III-IV n=14) with a PAXgene Blood RNA Kit. mRNA expression levels of each ARs was measured by Real-Time PCR following reaction conditions optimization. Based on recent guidelines three candidate reference genes (TOP2b, YWHAZ and SRP14) were selected to normalize mRNA expression data. An increase for each ARs (see Table 1) was observed as a function of clinical severity. To evaluate the catalyzation of the dephosphorylation of adenine nucleotides to adenosine in the extracellular space, the two cell surface molecules CD39 and CD73 were also evaluated and their transcript and resulted up-regulated. Significant correlations were observed between all ARs themselves. These findings show that components of adenosine metabolism and signalling are altered to promote adenosine production and signalling in HF patients. The increased expression of these ARs appears related to the severity of the disease, as indicated by the progressive rise in mRNA expression values with worsening of symptoms emphasizing a possible AR co-regulation. The increased CD39 and CD73 transcript levels suggests a protective CD39-CD73-dependent adenosine production in advanced HF patients. These data provide proof of the concept that adenosine-based drugs may play a role in the treatment of HF patients after confirmation by randomized clinical trials. See table on book abstracts