Document Detail

Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis.
MedLine Citation:
PMID:  23152112     Owner:  NLM     Status:  MEDLINE    
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.
Tomoko Ichiki; Guido Boerrigter; Brenda K Huntley; S Jeson Sangaralingham; Paul M McKie; Gail J Harty; Gerald E Harders; John C Burnett
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  304     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-03-05     Revised Date:  2014-01-23    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R102-9     Citation Subset:  IM    
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MeSH Terms
Blotting, Western
Cardiac Pacing, Artificial
Disease Models, Animal
Furin / genetics,  metabolism*
Heart Atria / enzymology,  pathology
Heart Failure / enzymology*,  genetics,  pathology
Heart Ventricles / enzymology*,  pathology
Myocardium / enzymology*,  pathology
Natriuretic Peptides / genetics,  metabolism*
Protein Precursors / genetics,  metabolism*
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Serine Endopeptidases / genetics,  metabolism*
Time Factors
Ventricular Remodeling
Grant Support
Reg. No./Substance:
0/Natriuretic Peptides; 0/Protein Precursors; 0/RNA, Messenger; EC 3.4.21.-/CORIN protein, human; EC 3.4.21.-/Serine Endopeptidases; EC protein, human; EC

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