title: Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts.
abstract: BACKGROUND
  Coronary artery bypass grafting is employed for the treatment of multiple-vessel lesions. Studies have shown that continued maladaptive remodelling expedites atherosclerosis and that excessive remodelling leads to graft restenosis. However, few studies have focussed on mechanistic target of rapamycin (mTOR) signalling involved during remodelling of transplanted veins.
  
  
  METHODS
  Rabbits were randomly allocated to groups undergoing vein-graft restenosis or sham surgery. At 1, 3, 7, 14, 28 and 90 days after surgery, we removed bypassed grafts and placed them in groups named T1, T2, T3, T4, T5and T6, respectively. Group T0denoted the control group. Analysis included vessel thickness, electron microscope data, TUNEL staining, and expression of the proliferation-associated gene proliferating cell nuclear antigen (PCNA). We chose specific time-points of gene expression, and then observed changes in the mTOR signalling.
  
  
  RESULTS
  The early stage of vein grafting (one to three days after surgery) led to apoptosis and degradation of the extracellular matrix. Seven days after surgery, cells began to proliferate. RICTOR expression in mTOR complex 2 (mTORC2) and that of its downstream substrate protein kinase C was enhanced in the early stage (T1and T3), and was higher in T1. mTORC1's upstream gene regulation decreased in T1and increased in T3. Its downstream genes eIF4b and 4E-BP showed similar changes. Expression of eIF4e and eIF4b increased, and led to an increase in protein composition.
  
  
  CONCLUSIONS
  After transplantation, mTORC1 function and its upstream and downstream genes were inhibited on the first day after grafting, but mTORC2 function was enhanced. One week after surgery, mTORC2 was still overexpressed when mTORC1 function had recovered and became enhanced. Hence, mTORC2 plays a major role in arterialisation of veins.
authors.affiliation: Department of Cardiovascular Surgery, Cardiovascular Research Institute Laboratory, First Hospital of Nanchang University, Nanchang 330000, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Cardiovascular Research Institute Laboratory, First Hospital of Nanchang University, Nanchang 330000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Basic Medical College, Nanchang University, Nanchang 330006, China.
authors.forename: Liqiao
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Cardiovascular Research Institute Laboratory, First Hospital of Nanchang University, Nanchang 330000, China. Electronic address: m17770086396_1@163.com.
authors.forename: Jichun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001026:Coronary Artery Bypass; D006083:Graft Occlusion, Vascular / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D066253:Vascular Remodeling; D014680:Veins / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: Vascular remodelling; Vein arterialisation; Vein graft restenosis; mTORC1/2