In vivo attenuation of myointimal hyperplasia using transforming growth factor-beta3 in an interposition graft model.
OBJECTIVE
To examine if transforming growth factor-beta3 (TGFbeta3) can attenuate the development of para-anastomotic myointimal hyperplasia in an animal model of small-diameter vascular graft failure.


METHODS
Under general anesthesia, 10 adult goats underwent bilateral polyurethane interposition graft insertion in the carotid position. Following completion of the anastomoses, each artery received adventitial infiltration of 50 ng of TGFbeta3 around the anastomoses; a placebo was administered to the other side. Postoperatively, each animal received 150 mg of aspirin daily. The arteries were explanted, half at 6 weeks and the remaining 5 at 3 months, for histological examination.


RESULTS
Vessel wall thickness surrounding the anastomosis was reduced by 37% in TGFbeta3-treated arteries compared to placebo at 6 weeks and 3 months, principally due to reduced smooth muscle cell proliferation. There was decreased overall luminal loss on angiography. Total collagen content was not significantly different between TGFbeta3 and placebo sides. Further analysis for the subendothelial matrix component collagen type VIII showed decreased levels on the treated side. Total elastin content was reduced on the TGFbeta3-treated side.


CONCLUSIONS
Direct single-dose subadventitial infiltration of TGFbeta3 following insertion of an interposition graft reduces SMC proliferation and elastin content. It would appear that TGFbeta3 holds promise as a prophylaxis against the development of myointimal hyperplasia, the predominant cause of graft failure in peripheral bypass surgery.
Murphy
Michael O
MO
Department of Vascular Surgery, Manchester Royal Infirmary, Manchester, UK.
Ghosh
Jonathan
J
Halka
Anatassi T
AT
Carter
Andrew
A
Turner
Neill J
NJ
Ferguson
Mark W J
MW
Kielty
Cay M
CM
Walker
Michael G
MG
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000714:Anastomosis, Surgical; D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D024102:Collagen Type VIII / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005260:Female; D006041:Goats; D006083:Graft Occlusion, Vascular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006965:Hyperplasia / Q000517:prevention & control; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology* / Q000627:therapeutic use; D014654:Vascular Patency
D000199:Actins; D024102:Collagen Type VIII; D012333:RNA, Messenger; D053782:Transforming Growth Factor beta3; D004549:Elastin