title: Expansive remodeling in venous bypass grafts: novel implications for vein graft disease.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Expansive lumenal remodeling is a novel mechanism of vein graft response to the arterial circulation, which is accelerated by a high cholesterol diet.
authors: Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: Amy P
authors: AP
authors: Wong
authors: Nafiseh
authors: N
authors: Nili
authors: Zane S
authors: ZS
authors: Jackson
authors: Beiping
authors: B
authors: Qiang
authors: Howard
authors: H
authors: Leong-Poi
authors: Ronen
authors: R
authors: Jaffe
authors: Ehud
authors: E
authors: Raanani
authors: Philip W
authors: PW
authors: Connelly
authors: John D
authors: JD
authors: Sparkes
authors: Bradley H
authors: BH
authors: Strauss
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D017536:Carotid Artery, Common / Q000601:surgery; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003094:Collagen / Q000096:biosynthesis; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D006083:Graft Occlusion, Vascular / Q000209:etiology*; D007601:Jugular Veins / Q000637:transplantation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011817:Rabbits; D012038:Regeneration; D017539:Tunica Intima / Q000166:cytology
chemical_list: D002791:Cholesterol, Dietary; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9