title: Amino-terminal fragment of C-type natriuretic peptide precursor and C-type natriuretic peptide do not correlate in patients with Chagas disease: role for neutral endopeptidase.
abstract: Atrial and B-type natriuretic peptides (ANP and BNP), but not C-type natriuretic peptide (CNP), have been identified to be diagnostic and prognostic markers in Chagas disease (CD). Although ANP and BNP excessively rise in patients with CD, increase in CNP is just minor. Our study aimed to investigate the mechanisms leading to CNP insensitivity to heart failure (HF) stimuli. Amino-terminal fragment of CNP precursor (NT-proCNP) and activity of neutral endopeptidase (NEP) were quantified to monitor CNP generation and degradation, respectively. Blood samples were collected from patients with CD and control healthy subjects. NT-proCNP concentrations were significantly lower in patients with CD without systolic dysfunction compared with healthy subjects. Despite a trend toward increase with rising heart failure clinical severity, it was significantly correlated with left ventricular ejection fraction and other echocardiographic parameters. As shown for CNP before, NT-proCNP could not predict mortality and heart transplant. Importantly, it had no statistical correlation with CNP. Additionally, NEP activity was significantly increased in New York Heart Association III and IV patients with HF but was positively correlated with CNP concentration. Our data demonstrates that generation of CNP is not enhanced under HF condition like CD. Thus, CNP rise by severe HF is caused by its less degradation that is independent of NEP activity.
authors.affiliation: Centre for Biomedical Research, Hull York Medical School, University of Hull, Hull, UK.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Maria da Consolação V
authors.initials: Mda C
authors.lastname: Moreira
authors.forename: Silvia
authors.initials: S
authors.lastname: Heringer-Walther
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Wolf-Eberhard
authors.initials: WE
authors.lastname: Siems
authors.forename: Niels
authors.initials: N
authors.lastname: Wessel
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D016022:Case-Control Studies; D014355:Chagas Disease / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: C480579:amino-terminal pro-C-type natriuretic peptide, human; D020098:Natriuretic Peptide, C-Type; D015260:Neprilysin