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

作者：Vodovar Nicolas; Seronde Marie France; Laribi Said; Gayat Etienne; Lassus Johan; Boukef Riadh; Nouira Semir; Manivet Philippe; Samuel Jane Lise; Logeart Damien; Ishihara Shiro; Solal Alain Cohen; Januzzi James L Jr; Richards A Mark; Launay Jean Marie^*; Mebazaa Alexandre

来源：European Heart Journal, 2014, 35(48): 3434-3441.

DOI：10.1093/eurheartj/ehu314

• Acute decompensated heart failure
• ProBNP
• BNP
• NT-proBNP
• Glycosylation
• Furin activity

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. %26lt;br%26gt;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 (rho = -0.62, P%26lt;0.001) but less so to BNP. In addition, we observed an increase in furin activity that is positively related to the plasma levels of proBNP, NT-proBNP and BNP overproduction (all P%26lt; 0.001, all rho%26gt;0.88), and negatively related to the degree of proBNP glycosylation (rho = 20.62, P%26lt;0.001). %26lt;br%26gt;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.

• 出版日期2014-12-21