[The expression of mammalian target of rapamycin and its substrates in autogenous vein graft in rats].
OBJECTIVE
To investigate the expression of mammalian target of rapamycin (mTOR) and its substrates including p70s6k and 4E-BP1 in autogenous vein graft.


METHODS
Autogenous vein graft model was established in 64 Wistar rats by transplanting the right common jugular vein to infrarenal abdominal aorta. Vein graft samples were harvested 6 hours, 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks after surgery. The mRNA expression of mTOR, p70s6k and 4E-BP1 were measured by RT-PCR and in situ hybridization. Western blot and immunohistochemistry methods also were used to detect the protein expression of mTOR, p70s6k and 4E-BP1. Proliferating cell nuclear antigen (PCNA) was also detected at the same time.


RESULTS
The mRNA expression of mTOR and p70s6k increased soon after vein graft transplanting, rose quickly and reached the peak 3 days to 2 weeks after surgery, which recovered 6 to 8 weeks after surgery. The expression of 4E-BP1 mRNA decreased soon after surgery and reached the lowest at 1 week, then rose to the peak 4 to 6 weeks after transplantation. Protein expression of mTOR and p70s6k reached the peak 2 to 4 weeks and recovered to normal level 8 weeks after surgery, but the expression of 4E-BP1 decreased to the lowest during 1 to 2 weeks and reached the peak 4 to 6 weeks after transplanting. The positive cells mostly located in vascular smooth muscle cell (VSMC) just like PCNA.


CONCLUSIONS
The expression of mTOR and its substrates were activated in vein graft soon after transplantation, which means that mTOR and its substrates might become new targets for the prevention and therapy of stenosis or obliteration after vein graft transplanting.
Hu
Xin-hua
XH
Department of Vascular Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, China. xinhuahu@126.com
Zhang
Qiang
Q
Yang
Jun
J
Liu
Cheng-wei
CW
Zhang
Zhi-shen
ZS
Wang
Jun
J
Liu
Ge-fei
GF
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007601:Jugular Veins / Q000637:transplantation*; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D014182:Transplantation, Autologous
D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011494:Protein Kinases; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases