title: Corin is present in the normal human heart, kidney, and blood, with pro-B-type natriuretic peptide processing in the circulation.
abstract: BACKGROUND
  B-type natriuretic peptide (BNP), which is activated in heart failure (HF), is processed to an active form by corin. The corin gene is expressed in the human heart and kidney, but corin protein expression in the heart, kidney, and circulation, along with whether proBNP is processed by circulating corin, remains unknown.
  
  
  METHODS
  We examined corin protein expression by immunostaining and Western blot in human heart and kidney, and we assessed the circulating corin concentration by ELISA. We examined histidine-tagged (His-tag) proBNP(1-108) processing in serum and plasma by immunoprecipitation and Western blot and sequenced the processed form.
  
  
  RESULTS
  Normal human heart and kidney displayed the presence of corin, especially in cells around the vasculature. Both corin and proBNP(1-108) were present in the plasma of healthy human subjects, with circulating corin significantly higher in men than women (P < 0.0001) and a positive correlation of corin to age (P = 0.0497, r = 0.27). In fresh normal plasma and serum, His-tag proBNP(1-108) was processed to a lower molecular weight form confirmed to be BNP. Processed BNP was higher in men than women (P = 0.041) and was positively correlated to plasma corin concentrations (P = 0.041, r = 0.65).
  
  
  CONCLUSIONS
  Our results support the concept that proBNP(1-108) may be processed outside of the heart in the circulation where the proprotein convertase is present. Moreover, sex may impact this process, since corin concentrations are higher in men. These findings may have important physiologic and pathophysiologic implications for the proBNP/corin system in the human.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, MN 55905, USA. ichiki.tomoko@mayo.edu
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichiki
authors.forename: Brenda K
authors.initials: BK
authors.lastname: Huntley
authors.forename: Denise M
authors.initials: DM
authors.lastname: Heublein
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Sandberg
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKie
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Martin
authors.forename: Michihisa
authors.initials: M
authors.lastname: Jougasaki
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000367:Age Factors; D001775:Blood Circulation; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D004492:Edetic Acid; D005260:Female; D006493:Heparin; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010949:Plasma; D011498:Protein Precursors / Q000097:blood*; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000097:blood; D044967:Serum; D012737:Sex Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor; D006493:Heparin; D004492:Edetic Acid; C119812:CORIN protein, human; D012697:Serine Endopeptidases