Inhibition of neointimal formation in porcine coronary artery by a Ras mutant

Background. Therapeutic approaches to reduce the neointimal formation cause d by balloon injury have been focused mainly on experimental models of rest enosis in the rat carotid artery, However, restenosis in rat carotid artery may not replicate the coronary arterial responses to injury in larger anim als and humans. Methods. In this study, we used pig coronary arteries as an animal model to evaluate the preventive effects of a virus-mediated dominant negative muta nt RasNI7 on balloon injury-induced restenosis. The viral particles were de livered to the balloon-injured coronary arteries via a dispatch catheter to keep the virus in a confined arterial segment for 10 min to reach optimal transfection, Six weeks after balloon injury, the pigs were sacrificed and the left anterior descending arteries were isolated for histological analys is. Results. Neointima formation was prominent in the group receiving balloon i njury as compared with the uninjured controls, A remodeling process with mi gration of collagen was also found in the injured coronary arteries. The ap plication of AdRasN17 led to a 56% decrease in neointima formation and a 75 % increase in lumen size, as compared with the balloon-injured vessels trea ted with AdLac Z control. Conclusions. These results suggest that AdRasN17 is an effective therapeuti c gene in preventing balloon injury-induced neointimal formation in pig cor onary arteries. (C) 2001 Academic Press.