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Expansive remodeling in venous bypass grafts: Novel implications for vein graft disease

  • Author Footnotes
    1 These authors contributed equally to this study.
    ,
    Author Footnotes
    2 Present address: Thoracic Surgery Research Laboratories, Max Bell Research Centre, McEwen Centre for Regenerative Medicine, Toronto General Hospital, Toronto, Canada.
    Amy P. Wong
    Footnotes
    1 These authors contributed equally to this study.
    2 Present address: Thoracic Surgery Research Laboratories, Max Bell Research Centre, McEwen Centre for Regenerative Medicine, Toronto General Hospital, Toronto, Canada.
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Author Footnotes
    1 These authors contributed equally to this study.
    ,
    Author Footnotes
    3 Present address: Isfahan University of Technology, Isfahan, Iran.
    Nafiseh Nili
    Footnotes
    1 These authors contributed equally to this study.
    3 Present address: Isfahan University of Technology, Isfahan, Iran.
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Zane S. Jackson
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Beiping Qiang
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Howard Leong-Poi
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Ronen Jaffe
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Ehud Raanani
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Philip W. Connelly
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • John D. Sparkes
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Bradley H. Strauss
    Correspondence
    Corresponding author at: Sunnybrook Health Sciences Centre, Schulich Heart Program, A253-2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5. Tel.: +1 416 480 6066; fax: +1 416 480 4745.
    Affiliations
    Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this study.
    2 Present address: Thoracic Surgery Research Laboratories, Max Bell Research Centre, McEwen Centre for Regenerative Medicine, Toronto General Hospital, Toronto, Canada.
    3 Present address: Isfahan University of Technology, Isfahan, Iran.

      Abstract

      Objective

      To date, intimal hyperplasia has been regarded as the principle mechanism responsible for subsequent vein graft disease. Lumen remodeling has not been previously considered as an additional mechanism. The objectives of this study were to determine changes in lumen remodeling in arterialized vein grafts, the accompanying cellular and extracellular matrix events contributing to remodeling, and the effects of a high cholesterol diet.

      Methods and results

      Reversed jugular vein-to-common carotid artery interposition grafts were constructed in 70 normocholesterolemic and 11 hypercholesterolemic male New Zealand white rabbits. The lumen area initially remained unchanged between 1 and 4 weeks but significantly increased by 40% at 12 weeks. This phase of expansive positive remodeling was accompanied by significantly increased cell apoptosis, collagen synthesis (1.7-fold), collagen content (3.7-fold), gelatinase (MMP-2 and MMP-9) levels and decreased tissue inhibitor of metalloproteinase (TIMP) levels. Expansive remodeling temporally corresponded to high macrophage infiltration and increased low density lipoprotein (LDL) retention (fourfold) in the vein grafts. A high cholesterol diet stimulated early macrophage infiltration and increased MMP-12 (metalloelastase) levels, which was associated with earlier onset of expansive remodeling.

      Conclusion

      Expansive lumenal remodeling is a novel mechanism of vein graft response to the arterial circulation, which is accelerated by a high cholesterol diet.

      Keywords

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