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Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression.

Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Research Abstract Details 

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  • Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Abstract Text:

    lamis hammoudLamis Hammoud,fuli xiangFuli Xiang,xiangru luXiangru Lu,friedrich brunnerFriedrich Brunner,kevin lecoKevin Leco,qingping fengQingping Feng,

    OBJECTIVE: We have recently demonstrated that endothelial nitric oxide synthase (eNOS) promotes cardiomyocyte proliferation. However, mechanisms by which eNOS regulates cardiomyocyte proliferation are not fully understood. The goal of the present study was to investigate the role of tissue inhibitor of metalloproteinase-3 (TIMP-3) in eNOS-mediated cardiomyocyte proliferation. METHODS AND RESULTS: Experiments were conducted in cultured neonatal mouse cardiomyocytes. TIMP-3 expression was significantly decreased in wild-type (WT) cardiomyocytes treated with an adenoviral eNOS (Ad-eNOS). Furthermore, TIMP-3 levels were significantly decreased in cardiomyocytes derived from eNOS transgenic mice. Conversely, TIMP-3 transcript levels were significantly elevated in eNOS(-/-) cardiomyocytes. The inhibitory effect of NO on TIMP-3 expression was dependent on S-nitrosylation of c-jun, a subunit of AP-1. Cell proliferation was increased in TIMP-3(-/-) cardiomyocytes while recombinant TIMP-3 decreased proliferation in both TIMP-3(-/-) and WT cardiomyocytes. Furthermore, the decline in proliferation observed in eNOS(-/-) cardiomyocytes was abrogated when TIMP-3 expression was blocked by an anti-TIMP-3 antibody. In vivo cardiomyocyte proliferation was assessed by Ki67 immunostaining on postnatal day 1 hearts. Ki67-positive cardiomyocytes were decreased in eNOS(-/-), but increased in eNOS-Tg and TIMP-3(-/-) hearts compared to WT controls. CONCLUSIONS: Our study suggests that eNOS promotes neonatal cardiomyocyte proliferation by inhibiting TIMP-3 expression.

    Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Publishing Authors By Initials

    l hammoudL Hammoud,f xiangF Xiang,x luX Lu,f brunnerF Brunner,k lecoK Leco,q fengQ Feng,

    For similar investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research

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    Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Cardiovascular research

    VOLUME: 75

    Page Numbers: 359-68

    Journal Abbreviation: Cardiovasc. Res.

    ISSN: 0008-6363

    DAY: 10

    MONTH: 05

    YEAR: 2007

    Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 77427

    Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Keywords Mesh Terms:

    KEYWORDS: Transduction, Genetic

    MESH TERMS: methods

    Chemical & Substance for Abstract: Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression. Information

    Substance Name: Nitric Oxide Synthase Type III

    Registry Number: EC 1.14.13.39

    Grant and Affiliation Information for Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation by inhibiting tissue inhibitor of metalloproteinase-3 expression.

    AFFILIATION: Lawson Health Research Institute, London, Ontario, Canada.

    Country: Netherlands

    Netherlands Research PublicationNetherlands Research Publication

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    MEDLINETA: Cardiovasc Res

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