Plasmin-mediated fibroblast growth factor-2 mobilisation supports smooth muscle cell proliferation in human saphenous vein

Sarah J. George, Jason L. Johnson, Melanie A. Smith, Christopher L. Jackson*

*Corresponding author for this work

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    29 Citations (Scopus)

    Abstract

    The focus of this study was identification of the contribution of the plasminogen activator-plasmin system to smooth muscle cell proliferation and migration in human saphenous vein. Segments of human saphenous vein were grown in organ culture for up to 14 days. Smooth muscle cell proliferation and migration were measured by incubating vein segments in bromodeoxyuridine, and smooth muscle cell death was detected by in situ end-labelling. Tissue-type (tPA) and urokinase-type (uPA) plasminogen activator enzymic activities were detectable in cultured saphenous vein segments, and were concentrated in focal zones. Inhibition of plasmin activity with α-N-acetyl-L-lysine methyl ester (NALME) or of uPA activity with a neutralising antibody caused significant decreases in smooth muscle cell proliferation in the media and the intima, but no significant changes in smooth muscle cell migration. Intimal thickness was also significantly decreased. Incubation with plasminogen or plasmin caused fibroblast growth factor-2 (FGF2) to be released into the medium. Addition of FGF2 to segments cultured with NALME reversed the inhibition of smooth muscle cell proliferation, and blocking the activity of FGF2 with a neutralising antibody caused a significant decrease in medial smooth muscle cell proliferation. These data suggest that plasmin mobilises FGF2 bound to the extracellular matrix of human saphenous vein, so that it can support smooth muscle cell proliferation and intimal thickening.

    Original languageEnglish
    Pages (from-to)492-501
    Number of pages10
    JournalJournal of Vascular Research
    Volume38
    Issue number5
    DOIs
    Publication statusPublished - 1 Dec 2001

    Keywords

    • Bypass graft
    • Extracellular matrix
    • Fibroblast growth factor
    • Plasmin
    • Saphenous vein
    • Smooth muscle cell

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