LOCAL-DELIVERY OF TGF-BETA ANTIBODIES TO PREVENT NEOINTIMA FORMATION AFTER BALLOON INJURY IN A PIG CORONARY-ARTERY MODEL

Background. The formation of neointima after vessel injury results fro m smooth muscle cell proliferation and extracellular matrix secretion. This process is activated by multiple growth factor release. Among th ese, Transforming Growth Factor-beta (TGF-beta) has been shown to play an important role. We hypothesized that local delivery of TGF-beta an tibodies could reduce neointima formation after balloon angioplasty. M ethods and Results. Using autoperfusion double-balloon catheters (Baxt er, Irvine, California), we infused polyclonal TGF-beta antibodies in 30 minutes, immediately after oversized balloon angioplasty in pig cor onary arteries. Eleven coronary arteries received 100 mu g anti-TGF-be ta and thirteen served as controls. Animals were sacrificed 10 weeks l ater; coronary segments were harvested and processed for histologic qu antitative assessment of the neointima. The extent of injury was simil ar in treated versus control vessels (39% +/- 5% vs. 30% +/- 4%) and t here was no difference in intimal thickening (0.63 +/- 0.19 mm for tre ated vs. 0.52 +/- 0.12 mm for controls). A previously validated resten osis injury index (ratio of neointimal area to total wall area over ex tent of injury) was also similar in both groups, 1.46 +/- 0.15 for tre ated versus 1.55 +/- 0.14 for controls. Conclusion. Local delivery of a single dose of TGF-beta antibodies failed to demonstrate a benefit o n neointima formation in a pig coronary artery model.