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Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis.

Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Research Abstract Details 

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  • Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Abstract Text:

    lacramioara ivanciuLacramioara Ivanciu,robert d gerardRobert D Gerard,haiwang tangHaiwang Tang,florea lupuFlorea Lupu,cristina lupuCristina Lupu,

    OBJECTIVE: Extracellular matrix (ECM) remodeling during angiogenesis is accomplished through plasmin-dependent pericellular proteolysis and through the action of matrix metalloproteinases (MMPs). Because tissue factor pathway inhibitor-2 (TFPI-2), a Kunitz-type protease inhibitor with prominent ECM localization, inhibits plasmin and MMPs activity, we investigated the role of TFPI-2 in endothelial cell (EC) migration and angiogenesis. METHODS AND RESULTS: Real-time polymerase chain reaction and immunostaining showed that the expression of TFPI-2 mRNA and protein was upregulated in migrating ECs. The effect of TFPI-2 on angiogenesis was studied in mouse models of Matrigel and polyvinylalcohol sponge implants by overexpressing TFPI-2 through infection with a replication-deficient adenovirus (AdTFPI-2). Using (immuno)fluorescence and confocal microscopy we observed that TFPI-2 reduced neovascularization and promoted ECM deposition. Lateral cell migration and capillary tube formation in vitro also were impaired by TFPI-2, a process reversed by anti-TFPI-2 antibodies. Increased apoptosis occurred both in AdTFPI-2-treated ECs and in the mouse implants. Zymography and assays in the absence of plasminogen confirmed plasmin inhibition as a main mechanism through which TFPI-2 inhibits EC migration. CONCLUSIONS: Our data suggest that TFPI-2 may be an important regulator of aberrant angiogenesis associated with tumor growth/metastasis, cardiovascular diseases, chronic inflammation, or diabetes.

    Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Publishing Authors By Initials

    l ivanciuL Ivanciu,rd gerardRD Gerard,h tangH Tang,f lupuF Lupu,c lupuC Lupu,

    For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

    PUBMED ID PMID:

    MEDLINE DATE:

    Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Arteriosclerosis, thrombosis, and vascular biology

    VOLUME: 27

    Page Numbers: 310-6

    Journal Abbreviation: Arterioscler. Thromb. Vasc. Bi

    ISSN: 1524-4636

    DAY: 30

    MONTH: 11

    YEAR: 2006

    Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 9505803

    Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Keywords Mesh Terms:

    KEYWORDS: Up-Regulation

    MESH TERMS: physiology

    Chemical & Substance for Abstract: Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Information

    Substance Name: tissue-factor-pathway inhibitor 2

    Registry Number: 0

    Grant and Affiliation Information for Adenovirus-mediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis.

    AFFILIATION: Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIGMS

    GRANT: 5R01GM037704-17

    ACRONYM: GM

    MEDLINETA: Arterioscler Thromb Vasc Biol

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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