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Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts.

Qun Wang1, Li Wan1, Liqiao Liu2

  • 1Department of Cardiovascular Surgery, Cardiovascular Research Institute Laboratory, First Hospital of Nanchang University, Nanchang 330000, China.

Heart, Lung & Circulation
|May 18, 2016
PubMed
Summary

Mechanistic target of rapamycin (mTOR) signaling in vein grafts shows early inhibition of mTORC1 and enhanced mTORC2 function. mTORC2 plays a key role in vein arterialization following transplantation.

Keywords:
Vascular remodellingVein arterialisationVein graft restenosismTORC1/2

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Area of Science:

  • Vascular biology
  • Cardiovascular surgery
  • Molecular signaling

Background:

  • Coronary artery bypass grafting treats multiple-vessel lesions.
  • Vein graft remodeling can lead to atherosclerosis and restenosis.
  • Mechanistic target of rapamycin (mTOR) signaling in vein graft remodeling is understudied.

Purpose of the Study:

  • To investigate the role of mechanistic target of rapamycin (mTOR) signaling in vein graft remodeling.
  • To elucidate the involvement of mTOR complexes in the arterialization process of transplanted veins.

Main Methods:

  • Rabbit models of vein-graft restenosis and sham surgery were used.
  • Grafts were analyzed at multiple time points (1-90 days) for vessel thickness, ultrastructure, apoptosis, and proliferation (PCNA).
  • Expression and activity of mTORC1 and mTORC2 signaling pathways were assessed.

Main Results:

  • Early vein grafting (1-3 days) induced apoptosis and extracellular matrix degradation.
  • Cell proliferation began around 7 days post-surgery.
  • mTORC2 (RICTOR) and its substrate PKC were enhanced early, while mTORC1 activity was initially inhibited then recovered and enhanced by day 7.

Conclusions:

  • mTORC1 function is inhibited early post-transplantation, whereas mTORC2 function is enhanced.
  • mTORC2 remains overexpressed one week after surgery when mTORC1 function recovers.
  • mTORC2 plays a significant role in the arterialization of veins after grafting.