Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-11-1
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1687-92
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Protease corin expression and activity in failing hearts.
pubmed:affiliation
Molecular Cardiology, Cardiovascular Medicine and Nephrology/Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural