title: First identification of circulating prepro-A-type natriuretic peptide (preproANP) signal peptide fragments in humans: initial assessment as cardiovascular biomarkers.
abstract: BACKGROUND
  New biomarkers are needed to assist clinical decision making in cardiovascular disease. We have recently shown that signal peptides may represent a novel biomarker target in cardiovascular diseases.
  
  
  METHODS
  We developed a novel immunoassay for the signal peptide of preproANP (ANPsp) and used it to document cardiac tissue levels of ANPsp in explant human hearts (n = 9), circulating venous concentrations of ANPsp in healthy volunteers (n = 65), temporal ANPsp concentrations in patients with ST-elevation myocardial infarction (STEMI) <4 h after chest pain onset (n = 23), and regional plasma ANPsp concentrations in patients undergoing clinically indicated catheterization (n = 10). We analyzed the structure and sequence of circulating ANPsp by tandem mass spectrometry (MS/MS).
  
  
  RESULTS
  ANPsp levels in human heart tissue were 50-1000 times lower than those of ANP/NT-proANP. ANPsp was detectable in control human plasma at concentrations comparable with ANP itself (approximately 20 ng/L). In STEMI patients, plasma concentrations of ANPsp rose to peak values at 5 h after symptom onset, significantly earlier than myoglobin, creatine kinase-MB, and troponin (P < 0.001). There were significant arteriovenous increases in ANPsp concentrations (P < 0.05) across the heart and kidney; arterial and coronary sinus concentrations of ANPsp both negatively correlated with systolic and mean arterial blood pressures (both P < 0.01). MS/MS verified circulating ANPsp to be preproANP(16-25) and preproANP(18-25).
  
  
  CONCLUSIONS
  ANPsp is a novel circulating natriuretic peptide with potential to act as a cardiovascular biomarker. The rapid increase of plasma ANPsp in STEMI and its significant relationship with blood pressure encourage further study of its potential clinical utility.
authors.affiliation: Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, New Zealand. chris.pemberton@otago.ac.nz
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Pemberton
authors.forename: Maithri
authors.initials: M
authors.lastname: Siriwardena
authors.forename: Torsten
authors.initials: T
authors.lastname: Kleffmann
authors.forename: Peter
authors.initials: P
authors.lastname: Ruygrok
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.forename: Tim G
authors.initials: TG
authors.lastname: Yandle
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007118:Immunoassay; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis; D009206:Myocardium / Q000378:metabolism; D021382:Protein Sorting Signals; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D021382:Protein Sorting Signals; D009320:Atrial Natriuretic Factor