Document Detail


Protease corin expression and activity in failing hearts.
MedLine Citation:
PMID:  20802129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Atrial and brain natriuretic peptides (ANP and BNP) regulate blood pressure and cardiac function. In patients with heart failure (HF), plasma levels of pro-ANP and pro-BNP, the precursor forms of ANP and BNP, are highly elevated, but the mechanism underlying the apparent deficiency in natriuretic peptide processing is unclear. Corin is a cardiac protease that activates natriuretic peptides. In this study, we examined corin protein expression and activity in mouse and human failing hearts. Tissue samples were obtained from a mouse model of HF induced by myotrophin overexpression and from human nonfailing, hypertrophic, and failing hearts. Corin protein levels in the membrane fraction and tissue lysate were measured by Western blotting and ELISA. Corin catalytic and biological activities were measured by fluorescent substrate and pro-ANP processing assays. In mice, corin protein levels did not change with age in normal hearts but increased significantly in failing hearts. In humans, corin protein levels were similar in the atrium from nonfailing and failing hearts but were increased in the ventricle in failing hearts compared with those in nonfailing or hypertrophic hearts. Unlike the protein level, however, corin activity did not increase in failing hearts, as measured by fluorogenic substrate and pro-ANP processing assays. Our results indicate that corin activation is a rate-limiting step in failing hearts. Insufficient corin activation is expected to prevent natriuretic peptide processing and may contribute to body fluid retention and impaired cardiac function in patients with HF.
Authors:
Shenghan Chen; Subha Sen; David Young; Wei Wang; Christine S Moravec; Qingyu Wu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-11-29     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1687-92     Citation Subset:  IM    
Affiliation:
Molecular Cardiology, Cardiovascular Medicine and Nephrology/Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Atrial Natriuretic Factor / metabolism
Blood Pressure / physiology
Disease Models, Animal
Female
Heart Failure / metabolism*,  physiopathology
Humans
Male
Mice
Mice, Transgenic
Middle Aged
RNA, Messenger / metabolism
Serine Endopeptidases / metabolism*
Grant Support
ID/Acronym/Agency:
HL089298-S1/HL/NHLBI NIH HHS; R01HL089298/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 85637-73-6/Atrial Natriuretic Factor; EC 3.4.21.-/CORIN protein, human; EC 3.4.21.-/Corin protein, mouse; EC 3.4.21.-/Serine Endopeptidases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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