Effects of active and negative mutants of Ras on rat arterial neointima formation

Background Ras protein is a key signal transducer in the cause of cell prol iferation. We studied the effects of active and negative mutants of the Ras gene on arterial neointimal formation in rats, with the aim of elucidating the molecular mechanisms regulating restenosis following percutaneous tran sluminal coronary angioplasty. Materials and methods. AdRasV12 and AdRasN17: the recombinant adenoviruses containing a constitutively active mutant and a dominant negative mutant of Ras, respectively, were used to determine whether Ras is necessary and suf ficient to modulate the smooth muscle cell proliferation and neointima form ation. Following balloon injury, rat common carotid arteries were treated i n their distal half with AdRasV12, AdRasN17, or AdLacZ, with the proximal b ah used as uninfected control. Results. In rat arteries subjected to balloon injury, either uninfected or treated with AdLacZ, there were pronounced SMC proliferation and neointima formation. These changes were markedly augmented by AdRasV12 and reduced by AdRasN17. Conclusion. Res is necessary and sufficient for SMC proliferation and neoin tima formation and may play a critical role in restenosis following balloon angioplasty. (C) 2000 Academic Press.