Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis

Am J Physiol Regul Integr Comp Physiol. 2013 Jan 15;304(2):R102-9. doi: 10.1152/ajpregu.00233.2012. Epub 2012 Nov 14.

Abstract

In heart failure (HF), the cardiac hormone natriuretic peptides (NPs) atrial (ANP), B-type (BNP), and C-type (CNP) play a key role to protect cardiac remodeling. The proprotein convertases corin and furin process their respective pro-NPs into active NPs. Here we define in a canine model of HF furin and corin gene and protein expression in normal and failing left atrium (LA) or ventricle (LV) testing the hypothesis that the NP proproteins convertases production is altered in experimental HF. Experimental canine HF was produced by rapid right ventricular pacing for 10 days. NPs, furin, and corin mRNA expression were determined by quantitative RT-PCR. Protein concentration or expression was determined by immunostaining, radioimmunoassay, or Western blot. Furin and corin proteins were present in normal canine LA and LV myocardium and vasculature and in smooth muscle cells. In normal canines, expression of NPs was dominant in the atrium compared with the ventricle. In experimental early stage HF characterized with marked atrial fibrosis, ANP, BNP, and CNP mRNA, and protein concentrations were higher in HF LA but not HF LV compared with normals. In LA, corin mRNA and protein expressions in HF were lower, whereas furin mRNA and protein expressions were higher than normals. NPs and furin expressions were augmented in the atrium in experimental early stage HF and, conversely, corin mRNA and protein expressions were decreased with atrial remodeling. Selective changes of these NP convertases may have significance in the regulation of pro-NP processing and atrial remodeling in early stage HF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cardiac Pacing, Artificial
  • Disease Models, Animal
  • Dogs
  • Fibrosis
  • Furin / genetics
  • Furin / metabolism*
  • Heart Atria / enzymology
  • Heart Atria / pathology
  • Heart Failure / enzymology*
  • Heart Failure / genetics
  • Heart Failure / pathology
  • Heart Ventricles / enzymology*
  • Heart Ventricles / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Myocardium / enzymology*
  • Myocardium / pathology
  • Natriuretic Peptides / genetics
  • Natriuretic Peptides / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Time Factors
  • Ventricular Remodeling

Substances

  • Natriuretic Peptides
  • Protein Precursors
  • RNA, Messenger
  • CORIN protein, human
  • Serine Endopeptidases
  • FURIN protein, human
  • Furin