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  • The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty and stenting

    Author(s)
    Murrell, Melanie
    Khachigian, Levon
    Ward, Michael R.
    Griffith University Author(s)
    Murrell, Melanie J.
    Year published
    2007
    Metadata
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    Abstract
    Restenosis after balloon angioplasty and stenting is exacerbated by low flow. Flow-dependent restenosis after angioplasty but not stenting is prevented by the antioxidant pyrrolidine dithiocarbamate (PDTC). c-jun may play a role in these events as AP-1 activity is both flow and redox sensitive. Carotid arteries of cholesterol fed rabbits underwent stenting or balloon injury in the presence of low or normal flow. c-jun mRNA expression was enhanced by low flow and injury (stent > balloon) and inhibited by the antioxidant PDTC irrespective of the injury type. The effect of locally delivered DZ13 (a DNAzyme specific for c-jun) ...
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    Restenosis after balloon angioplasty and stenting is exacerbated by low flow. Flow-dependent restenosis after angioplasty but not stenting is prevented by the antioxidant pyrrolidine dithiocarbamate (PDTC). c-jun may play a role in these events as AP-1 activity is both flow and redox sensitive. Carotid arteries of cholesterol fed rabbits underwent stenting or balloon injury in the presence of low or normal flow. c-jun mRNA expression was enhanced by low flow and injury (stent > balloon) and inhibited by the antioxidant PDTC irrespective of the injury type. The effect of locally delivered DZ13 (a DNAzyme specific for c-jun) or scrambled DZ13 (inactive DNAzyme) was assessed by histomorphometry at 28 days. Low flow significantly increased intimal hyperplasia in B and S relative to normal flow (P < 0.05). The active DNAzyme DZ13 markedly reduced intimal hyperplasia (P < 0.001) and increased lumen size (P < 0.05) in balloon-injured but not in stented segments, and abrogated the effect of low flow on restenosis after angioplasty, similar to the morphological effects of PDTC. We conclude that c-jun expression is enhanced by low flow and by injury (stent > balloon) and markedly attenuated by PDTC, and that c-jun is an important mediator of flow-dependent restenosis in balloon-injured but not stented vessels.
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    Journal Title
    Atherosclerosis
    Volume
    194
    Issue
    2
    DOI
    https://doi.org/10.1016/j.atherosclerosis.2006.11.016
    Subject
    Clinical Sciences not elsewhere classified
    Cardiorespiratory Medicine and Haematology
    Clinical Sciences
    Publication URI
    http://hdl.handle.net/10072/33484
    Collection
    • Journal articles

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