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

Tomoko Ichiki, Guido Boerrigter, Brenda K. Huntley, S Jeson Sangaralingham, Paul McKie, Gail J. Harty, Gerald E. Harders, John C Jr. Burnett

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume304
Issue number2
DOIs
StatePublished - Jan 15 2013

Fingerprint

Furin
Natriuretic Peptides
Fibrosis
Heart Failure
Heart Atria
Canidae
Atrial Natriuretic Factor
Messenger RNA
Proprotein Convertases
Atrial Remodeling
Heart Ventricles
Proteins
Smooth Muscle Myocytes
Radioimmunoassay
Myocardium
Western Blotting

Keywords

  • Atrial fibrosis
  • Corin
  • Furin
  • Heart failure
  • Natriuretic peptides

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

@article{fcb3aa85d98748c7beb4099aba732e68,
title = "Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis",
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.",
keywords = "Atrial fibrosis, Corin, Furin, Heart failure, Natriuretic peptides",
author = "Tomoko Ichiki and Guido Boerrigter and Huntley, {Brenda K.} and Sangaralingham, {S Jeson} and Paul McKie and Harty, {Gail J.} and Harders, {Gerald E.} and Burnett, {John C Jr.}",
year = "2013",
month = "1",
day = "15",
doi = "10.1152/ajpregu.00233.2012",
language = "English (US)",
volume = "304",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis

AU - Ichiki, Tomoko

AU - Boerrigter, Guido

AU - Huntley, Brenda K.

AU - Sangaralingham, S Jeson

AU - McKie, Paul

AU - Harty, Gail J.

AU - Harders, Gerald E.

AU - Burnett, John C Jr.

PY - 2013/1/15

Y1 - 2013/1/15

N2 - 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.

AB - 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.

KW - Atrial fibrosis

KW - Corin

KW - Furin

KW - Heart failure

KW - Natriuretic peptides

UR - http://www.scopus.com/inward/record.url?scp=84872402330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872402330&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00233.2012

DO - 10.1152/ajpregu.00233.2012

M3 - Article

C2 - 23152112

AN - SCOPUS:84872402330

VL - 304

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 2

ER -