Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure

Background Increases in plasma B-type natriuretic peptide (BNP) concentrations in those with acutely decompensated heart failure (ADHF) has been mainly attributed to an increase in NPPB gene transcription. Recently, proBNP glycosylation has emerged as a potential regulatory mechanism in the production of amino-terminal (NT)-proBNP and BNP. The aim of the present study was to investigate proBNP glycosylation, and corin and furin activities in ADHF patients. Methods and results Plasma levels of proBNP, NT-proBNP, BNP, as well as corin and furin concentration and activity were measured in a large cohort of 683 patients presenting with ADHF ( n = 468), non-cardiac dyspnoea (non-ADHF: n = 169) and 46 patients with stable chronic heart failure (CHF); the degree of plasma proBNP glycosylation was assessed in a subset of these patients (ADHF: n = 49, non-ADHF: n = 50, CHF: n = 46). Our results showed a decrease in proBNP glycosylation in ADHF patients that paralleled NT-proBNP overproduction ( ρ = −0.62, P 0.88), and negatively related to the degree of proBNP glycosylation (ρ = −0.62, P < 0.001). Conclusion These comprehensive results provide a paradigm for the post-translational modification of natriuretic peptides in ADHF: as proBNP glycosylation decreases, furin activity increases. This synergistically amplifies the processing of proBNP into BNP and NT-proBNP. Clinical Trial Registration . Identifier: [NCT01374880][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01374880&atom=%2Fehj%2Fearly%2F2014%2F10%2F06%2Feurheartj.ehu314.atom