Transcriptome profiling of natriuretic peptide system in cardiac tissue of patients with idiopathic or ischemic end-stage dilated cardiomyopathy

Purpose: Circulating levels of Natriuretic Peptides (NPs) play a role as reliable biomarkers of disease stage in patients with heart failure (HF). However, while several studies are present in literature about their circulating levels, only few data on the RNA expression have been reported and it is still debated whether the myocardial levels of NPs change in relation to etiology of cardiomyopathy in patients with similar left ventricular (LV) function. The aim of the study was to analyze the transcriptome profiling of NPs system in LV tissue of patients affected by idiopathic (DCM) or ischemic (ICM) end-stage dilated cardiomyopathy undergoing cardiac transplantation. Methods: Transcriptomic profile of NP system and of relative reference genes (RPS4X, eEF1a, RPL13a) was measured in LV myocardium of DCM (n=8; age: <50yrs; LVEF%=17.5±3; LVEDV=305.5±110ml) and ICM pts (n=8; age: <50yrs; LVEF%=19.5±5.2; LVEDV=270±97 ml) with similar cardiac function by Real-Time PCR analysis. All patients received similar medications and cardiac function was assessed by echocardiography. As control (C, n=5) atrial cardiac tissue samples of age and sex matched subjects with LVEF% ≥50 were analyzed. Results: All myocardial NPs resulted expressed in both DCM and ICM patients, yet BNP was the main expressed NP. In particular, ANP (DCM:0.445±0.26; ICM:0.077±0.05) and BNP (DCM:9.89±1.92; ICM:3.29±1.4, p=0.007) resulted higher in DCM compared to ICM, while CNP was more higher in ICM, even though not significantly (DCM:0.864±0.4; ICM:1.85±0.99). All NP receptors were expressed in both groups. Even though BNP and CNP levels were higher in both failing hearts compared to C, between the NP receptors only NPR-B resulted increased in DCM (p<0,0001 C vs. DCM). Significant correlations were observed between BNP and NPR-A, NPR-B and NPR-C (p=0.022 and p=0.044, p<0.0001 respectively). Conclusions: Our results show, in the presence of similar decay of the LV function, an activation of the entire NP system reporting a different involvement in cardiac tissue of ICM/DCM patients and underlining a different trend for CNP mRNA expression. Even though more studies are necessary to better explain the role of CNP in the setting of cardiomyopathies, these findings support the future use of CNP as a new target in the treatment of ischemic disorders, thanks to its protective effects. Moreover its different transcriptomic levels, depending on the aetiology, together with the activation of its specific receptor, NPR-B, could be used in future clinical application as important diagnostic tool.