Details

Autor(en) / Beteiligte

• Vodovar, Nicolas
• Séronde, Marie-France
• Laribi, Said
• Gayat, Etienne
• Lassus, Johan
• Boukef, Riadh
• Nouira, Semir
• Manivet, Philippe
• Samuel, Jane-Lise
• Logeart, Damien
• Ishihara, Shiro
• Cohen Solal, Alain
• Januzzi, Jr, James L
• Richards, A Mark
• Launay, Jean-Marie
• Mebazaa, Alexandre

Titel

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

Ist Teil von

• European heart journal, 2014-12, Vol.35 (48), p.3434-3441

Ort / Verlag

England

Erscheinungsjahr

2014

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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. 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 < 0.001) 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 < 0.001, all ρ > 0.88), and negatively related to the degree of proBNP glycosylation (ρ = -0.62, P < 0.001). 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. http://clinicaltrials.gov/. Identifier: NCT01374880.