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http://purl.uniprot.org/citations/10435007http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10435007http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Tissue inhibitors of metalloproteinases (TIMPs) are downregulated in the failing human heart. The objective of the present study was to test the hypothesis that cytokines might be involved in the regulation of TIMPs in cardiac cells.

Methods

Neonatal Sprague-Dawley rat ventricular cells were exposed to 100 units/ml tumor necrosis factor-alpha and/or 5 ng/ml interleukin-1 beta. The mRNA and protein expression of TIMPs-1-4 and disintegrin metalloproteinase was analyzed using Northern blot, ELISA and/or Western blot, respectively. Proteolytic activity and extracellular matrix degradation and turnover were determined using gelatin zymography and pulse-chase experiments.

Results

The TIMP-1 mRNA was upregulated in cardiac cells, while TIMP-1 protein levels were unchanged in myocytes but downregulated in non-myocytes. The TIMP-2 expression did not change with the cytokine treatment. TIMP-3 was downregulated at both the mRNA and protein levels in cardiac cells. TIMP-4 protein was transiently increased and then returned to control level. In contrast, disintegrin metalloproteinase mRNA and protein were significantly upregulated in those cells. The gelatinolytic activity and extracellular matrix protein degradation were significantly increased.

Conclusions

Tumor necrosis factor-alpha and interleukin-1 beta regulate the expression of TIMPs and disintegrin metalloproteinase, which may in turn contribute to the increased matrix degradation in cardiac cells. Since heart failure in humans is characterized by both re-expression of myocardial cytokines and remodeling of the extracellular matrix, those in vitro results suggest a potential role for those cytokines in the regulation of extracellular matrix remodeling and therefore in the transition to the end-stage heart failure phenotype."xsd:string
http://purl.uniprot.org/citations/10435007http://purl.org/dc/terms/identifier"doi:10.1016/s0008-6363(98)00297-1"xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/author"Li Y.Y."xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/author"Feldman A.M."xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/author"McTiernan C.F."xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/name"Cardiovasc Res"xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/pages"162-172"xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/title"Proinflammatory cytokines regulate tissue inhibitors of metalloproteinases and disintegrin metalloproteinase in cardiac cells."xsd:string
http://purl.uniprot.org/citations/10435007http://purl.uniprot.org/core/volume"42"xsd:string
http://purl.uniprot.org/citations/10435007http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10435007
http://purl.uniprot.org/citations/10435007http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10435007
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http://purl.uniprot.org/uniprot/#_P03957-mappedCitation-10435007http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/10435007
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http://purl.uniprot.org/uniprot/A0A8L2Q5Q1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/10435007
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