title: Evidence for functional heterogeneity of circulating B-type natriuretic peptide.
abstract: OBJECTIVE
  These studies describe molecular forms of circulating B-type natriuretic peptide (BNP) as well as their biological activity.
  
  
  BACKGROUND
  Increased circulating levels of immunoreactive BNP correlate with the severity of heart failure and are considered a sensitive biomarker. However, little is known about the molecular forms of circulating BNP and their biological activity.
  
  
  METHODS
  Western blot analysis was used to characterize immunoreactive BNP species in heart failure plasma. Recombinant proBNP was assessed for reactivity in commercially available BNP assays and cell activity by cyclic guanosine monophosphate production in vascular cells.
  
  
  RESULTS
  Heart failure plasma contained both low- (LMW-BNP) and high-molecular-weight (HMW-BNP) forms. The LMW-BNP migrated similarly to a 32-amino acid BNP standard, whereas HMW-BNP, when deglycosylated, was similar to deglycosylated recombinant proBNP. Recombinant proBNP and BNP were equally recognized by the Triage BNP assay (Biosite, San Diego, California). Furthermore, recombinant proBNP and BNP were both recognized by the Advia Centaur BNP test (Bayer Diagnostics, Tarrytown, New York), but only recombinant proBNP was recognized by the Elecsys NTproBNP assay (Roche Diagnostics, Indianapolis, Indiana). Recombinant proBNP exerted significantly less biological activity than BNP on human endothelial and vascular smooth muscle cells. Comparison of effective concentration (50%) values indicates that proBNP is 6- to 8-fold less potent than BNP in these human cells.
  
  
  CONCLUSIONS
  This study demonstrates that proBNP, constituting a substantial portion of immunoreactive BNP in heart failure plasma, possesses significantly lower biological activity than the processed 32-amino acid hormone. These results implicate a discordance in heart failure between the high circulating levels of immunoreactive BNP and hormone activity, suggesting that some patients may be in a state of natriuretic peptide deficiency.
authors.affiliation: Scios, Inc., Fremont, California 94555, USA.
authors.forename: Faquan
authors.initials: F
authors.lastname: Liang
authors.forename: Jessica
authors.initials: J
authors.lastname: O'Rear
authors.forename: Ute
authors.initials: U
authors.lastname: Schellenberger
authors.forename: Lungkuo
authors.initials: L
authors.lastname: Tai
authors.forename: Michael
authors.initials: M
authors.lastname: Lasecki
authors.forename: George F
authors.initials: GF
authors.lastname: Schreiner
authors.forename: Fred S
authors.initials: FS
authors.lastname: Apple
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.forename: N Stephen
authors.initials: NS
authors.lastname: Pollitt
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Protter
mesh_terms: D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D018450:Disease Progression; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D047468:Immunoprecipitation; D008967:Molecular Biology; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D018076:DNA, Complementary; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain