title: Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure.
abstract: 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.
  
  
  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 < 0.001) 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  http://clinicaltrials.gov/. Identifier: NCT01374880.
authors.affiliation: UMRS 942 Inserm, Paris 75010, France DHU FIRE.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vodovar
authors.affiliation: UMRS 942 Inserm, Paris 75010, France Department of Cardiology, EA3920, University Hospital Jean Minjoz, Besançon, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Séronde
authors.affiliation: UMRS 942 Inserm, Paris 75010, France Department of Emergency Medicine, Lariboisière Hospital, Paris, France DHU Neurovasc.
authors.forename: Said
authors.initials: S
authors.lastname: Laribi
authors.affiliation: UMRS 942 Inserm, Paris 75010, France DHU Neurovasc Department of Anesthesiology and Intensive Care, Lariboisière Hospital, 2, Rue A. Paré, 75475 Paris, Cedex 10, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Gayat
authors.affiliation: Heart and Lung Center, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Johan
authors.initials: J
authors.lastname: Lassus
authors.affiliation: Emergency Department and Research Unit UR06SP21, Fattouma Bourguiba University Hospital, Monastir, Tunisia.
authors.forename: Riadh
authors.initials: R
authors.lastname: Boukef
authors.affiliation: Emergency Department and Research Unit UR06SP21, Fattouma Bourguiba University Hospital, Monastir, Tunisia.
authors.forename: Semir
authors.initials: S
authors.lastname: Nouira
authors.affiliation: UMRS 942 Inserm, Paris 75010, France Department of Biochemistry, Lariboisière Hospital, 2, Rue A. Paré, 75475, Paris, Cedex 10, France Center for Biological Resources, Lariboisière Hospital, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Manivet
authors.affiliation: UMRS 942 Inserm, Paris 75010, France Department of Anesthesiology and Intensive Care, Lariboisière Hospital, 2, Rue A. Paré, 75475 Paris, Cedex 10, France.
authors.forename: Jane-Lise
authors.initials: JL
authors.lastname: Samuel
authors.affiliation: UMRS 942 Inserm, Paris 75010, France DHU FIRE Department of Cardiology, Lariboisière Hospital, Paris, France Paris Diderot University, Sorbonne Paris Cité, Paris 75205, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Logeart
authors.affiliation: UMRS 942 Inserm, Paris 75010, France Cardiology and Intensive Care Unit, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ishihara
authors.affiliation: UMRS 942 Inserm, Paris 75010, France DHU FIRE Department of Cardiology, Lariboisière Hospital, Paris, France Paris Diderot University, Sorbonne Paris Cité, Paris 75205, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Cohen Solal
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: University of Otago, Christchurch, New Zealand National University Health System, Singarpore, Singapore.
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.affiliation: UMRS 942 Inserm, Paris 75010, France Department of Biochemistry, Lariboisière Hospital, 2, Rue A. Paré, 75475, Paris, Cedex 10, France Center for Biological Resources, Lariboisière Hospital, Paris, France alexandre.mebazaa@lrb.ap-hp.fr alexandre.mebazaa@lrb.aphp.fr.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.affiliation: UMRS 942 Inserm, Paris 75010, France DHU Neurovasc Department of Anesthesiology and Intensive Care, Lariboisière Hospital, 2, Rue A. Paré, 75475 Paris, Cedex 10, France Paris Diderot University, Sorbonne Paris Cité, Paris 75205, France alexandre.mebazaa@lrb.ap-hp.fr alexandre.mebazaa@lrb.aphp.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
mesh_terms: D000208:Acute Disease; D000368:Aged; D015331:Cohort Studies; D004417:Dyspnea / Q000209:etiology; D005260:Female; D045683:Furin / Q000378:metabolism; D006031:Glycosylation; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C119812:CORIN protein, human; D012697:Serine Endopeptidases; D045683:Furin
keywords: Acute decompensated heart failure; BNP; Furin activity; Glycosylation; NT-proBNP; ProBNP