Linked Life Data

18436234

Source:http://linkedlifedata.com/resource/pubmed/id/18436234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-9
pubmed:abstractText
Myocardial matrix remodeling is a well-recognized disease modifier in the pathogenesis of heart failure, although the precise underlying molecular mechanisms remain to be elucidated. Here we investigated the effects of leptin, circulating levels of which are typically increased in obese individuals, on MMP and collagen expression and MMP activity in isolated cardiac myofibroblasts. Neonatal rat myofibroblasts were treated with 6 nM recombinant leptin and the collected supernatant analyzed for MMP-2 activity via gelatin zymography. MMP-2, MT1-MMP and procollagen-I and -III protein expression were determined by western blotting and MMP-2 and MT1-MMP mRNA expression were examined utilizing real-time PCR. Procollagen-I levels were analyzed by confocal microscopy and collagen synthesis was determined through [(3)H]-proline incorporation. Exposure of myofibroblasts to leptin (24 h) significantly increased MMP-2 activity, while mRNA and protein levels remained unchanged. Leptin also significantly enhanced mRNA and protein expression of MT1-MMP, a known activator of MMP-2. Biotinylation assays indicated increased cell surface expression of MT1-MMP in response to leptin and use of a MT1-MMP inhibitor attenuated the leptin-mediated elevation of MMP-2 activity. Total cellular collagen synthesis was unaffected by leptin treatment, however intracellular procollagen-I protein was significantly increased in treated cells. Furthermore, extracellular soluble procollagen-I was increased, while a decrease in soluble procollagen-III protein was observed in conditioned media. In summary, these findings in isolated cardiac myofibroblasts support the suggestion that leptin may directly influence myocardial matrix metabolism, and this may represent a mechanism contributing to cardiac fibrosis in obese patients with elevated plasma leptin levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1095-8584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
874-81
pubmed:meshHeading
pubmed-meshheading:18436234-Animals, pubmed-meshheading:18436234-Animals, Newborn, pubmed-meshheading:18436234-Cell Membrane, pubmed-meshheading:18436234-Collagen Type I, pubmed-meshheading:18436234-Collagen Type III, pubmed-meshheading:18436234-Enzyme Activation, pubmed-meshheading:18436234-Extracellular Space, pubmed-meshheading:18436234-Fibroblasts, pubmed-meshheading:18436234-Gelatin, pubmed-meshheading:18436234-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18436234-Intracellular Space, pubmed-meshheading:18436234-Leptin, pubmed-meshheading:18436234-Matrix Metalloproteinase 14, pubmed-meshheading:18436234-Matrix Metalloproteinase 2, pubmed-meshheading:18436234-Mice, pubmed-meshheading:18436234-Myocardium, pubmed-meshheading:18436234-Proline, pubmed-meshheading:18436234-Protein Transport, pubmed-meshheading:18436234-RNA, Messenger, pubmed-meshheading:18436234-Rats, pubmed-meshheading:18436234-Rats, Sprague-Dawley
pubmed:year
2008
pubmed:articleTitle
Increased expression and cell surface localization of MT1-MMP plays a role in stimulation of MMP-2 activity by leptin in neonatal rat cardiac myofibroblasts.
pubmed:affiliation
York University, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't