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 proliferation. 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 transluminal coronary angioplasty.


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 sufficient to modulate the smooth muscle cell proliferation and neointima formation. Following balloon injury, rat common carotid arteries were treated in their distal half with AdRasV12, AdRasN17, or AdLacZ, with the proximal half 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.


CONCLUSIONS
Ras is necessary and sufficient for SMC proliferation and neointima formation and may play a critical role in restenosis following balloon angioplasty.
Jin
G
G
Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, La Jolla, California 92093-0427, USA.
Chieh-Hsi Wu
J
J
Li
Y S
YS
Hu
Y L
YL
Shyy
J Y
JY
Chien
S
S
D000256:Adenoviridae; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000502:physiology; D017536:Carotid Artery, Common / Q000473:pathology / Q000502:physiology*; D016893:Carotid Stenosis / Q000473:pathology / Q000628:therapy; D002404:Catheterization; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D011905:Genes, ras; D008297:Male; D009154:Mutation; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology*