Reduction of myointimal hyperplasia after arterial anastomosis by local injection of transforming growth factor beta3.
BACKGROUND
The transforming growth factor (TGF)-beta family of cytokines exerts pleiotropic actions on vascular smooth muscle cell phenotype, proliferation, and extracellular matrix synthesis. This in vivo study assessed the use of TGF-beta3 in attenuating the development of postanastomotic smooth muscle cell proliferation.


METHODS
Under general anesthesia, 10 adult goats underwent transection and reanastomosis of both common carotid arteries. After reanastomosis, one artery was infiltrated with 50 ng of TGF-beta3 in 100 microL of pH buffer around the anastomosis, and the other side was infiltrated with buffer only. After surgery, each animal received 150 mg of aspirin daily. The arteries were explanted after 3 months for histologic examination.


RESULTS
Vessel wall thickness surrounding the anastomosis was reduced by 30% after TGF-beta3 treatment compared with placebo (P = .003), with a 20% (P = .002) reduction in cellular content. Although total collagen content was not significantly different between TGF-beta3 and placebo, collagen type VIII content was reduced around the TGF-beta3 anastomoses (P = .011). A reduction in the total elastin content (P = .003) and number of elastic fiber lamellae (P = .042) was found surrounding TGF-beta3-treated anastomoses, but not placebo-treated anastomosis. A 29% increase in vasa vasorum (P = .044) was present around TGF-beta3-treated anastomoses. No differences in inflammatory cell infiltration were seen between sides.


CONCLUSIONS
Direct subadventitial infiltration of TGF-beta3 immediately after creation of an arterial anastomosis attenuates cell proliferation, with a reduction in elastin and collagen type VIII content and vessel wall thickness.
Ghosh
Jonathan
J
Department of Vascular Surgery, Manchester Royal Infirmary, Manchester, UK.
Baguneid
Mohammed
M
Khwaja
Nadeem
N
Murphy
Michael O
MO
Turner
Neill
N
Halka
Anatassi
A
Ferguson
Mark W
MW
Kielty
Cay M
CM
Walker
Michael G
MG
D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D001158:Arteries / Q000601:surgery*; D005260:Female; D006041:Goats; D006965:Hyperplasia / Q000517:prevention & control; D015552:Injections, Intralesional; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D011183:Postoperative Complications / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D053782:Transforming Growth Factor beta3; D017539:Tunica Intima / Q000473:pathology*
D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3