Reduction of myointimal hyperplasia after arterial anastomosis by local injection of transforming growth factor β3

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-beta 3 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-beta 3 in 100 mu L 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-beta 3 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-beta 3 and placebo, collagen type VIII content was reduced around the TGF-beta 3 anastomoses (P =.011). A reduction in the total elastin content (P =.003) and number of elastic fiber lamellae (P =.042) was found surrounding TGF-beta 3-treated anastomoses, but not placebo-treated anastomosis. A 29% increase in vasa vasorum (P =.044) was present around TGF-beta 3-treated anastomoses. No differences in inflammatory cell infiltration were seen between sides. Conclusions. Direct subadventitial infiltration of TGF-beta 3 immediately after creation of an arterial anastomosis attenuates cell proliferation, with a reduction in elastin and collagen type VIII content and vessel wall thickness.