title: Secretion of prohormone of B-type natriuretic peptide, proBNP1-108, is increased in heart failure.
abstract: OBJECTIVE
  Using a novel, specific assay for proBNP(1-108), this study tested the hypotheses that proBNP(1-108) is secreted by both nonfailing and failing human hearts and that proBNP(1-108) secretion is increased in failing hearts.
  
  
  BACKGROUND
  The prohormone of B-type natriuretic peptide (proBNP(1-108)) is a 108-amino acid peptide produced primarily by the heart and cleaved into biologically active BNP(1-32) and the biologically inactive NT-proBNP(1-76). It is unknown to what extent increased cardiac proBNP1-108 secretion compared to reduced peripheral processing is responsible for elevated proBNP(1-108) levels in patients with heart failure (HF) compared to subjects without HF.
  
  
  METHODS
  The transcardiac gradient of proBNP(1-108) was determined by collecting arterial blood and blood from the coronary sinus (CS). Samples from subjects without overt heart disease (n = 9) were collected during cardiac catheterization after coronary artery disease had been excluded. Samples from HF patients (n = 21) were collected during implantation of a biventricular pacemaker. ProBNP(1-108) was measured with a new assay. Values are medians (25th/75th percentiles).
  
  
  RESULTS
  The gradient of proBNP(1-108) across the nonfailing hearts was 8 (2/20) ng/l (aorta: 15 [1/25] ng/l; CS: 24 [8/41] ng/l; p = 0.018). The transcardiac gradient of proBNP(1-108) in the failing hearts was 326 (96/482) ng/l (arterial: 381 [201/586] ng/l; CS: 709 [408/1,087] ng/l; p<0.001). The transcardiac gradient was greater in failing than nonfailing hearts (p = 0.001).
  
  
  CONCLUSIONS
  ProBNP(1-108) is secreted by nonfailing and failing human hearts, but more so in the latter. It remains to be established where peripheral processing of proBNP(1-108) occurs and how this is affected by disease.
authors.affiliation: Mayo Clinic, Rochester, Minnesota. Electronic address: costello.boerrigter@gmail.com.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Costello-Boerrigter
authors.affiliation: Helios Clinic, Erfurt, Germany; Witten/Herdecke University, Faculty of Health, School of Medicine, Witten, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Lapp
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Guido
authors.initials: G
authors.lastname: Boerrigter
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: Helios Clinic, Wuppertal, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bufe
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Fima
authors.initials: F
authors.lastname: Macheret
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Heublein
authors.affiliation: Bio-Rad, Marnes-la-Coquette, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Larue
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000368:Aged; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood* / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: biomarker; heart failure; natriuretic peptides; proBNP(1-108)