Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo.
Proliferation of smooth muscle cells of the arterial wall in response to local injury is an important aetiologic factor of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. Ras proteins are key transducers of mitogenic signals from membrane to nucleus in many cell types. We investigated the role of ras proteins in the vascular response to arterial injury by inactivating cellular ras of rats in which the common carotid artery was subjected to balloon injury. DNA vectors expressing ras transdominant negative mutants, which interfere with ras function, reduced neointimal formation after injury. Our results indicate a key role for ras in smooth muscle cell proliferation and show that the local delivery of transdominant negative mutants of ras in vivo might prevent some of the acute vascular injury caused by balloon injury.
Indolfi
C
C
Cattedra di Cardiologia, Università degli Studi di Napoli Federico II, Italy.
Avvedimento
E V
EV
Rapacciuolo
A
A
Di Lorenzo
E
E
Esposito
G
G
Stabile
E
E
Feliciello
A
A
Mele
E
E
Giuliano
P
P
Condorelli
G
G
D000818:Animals; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics / Q000627:therapeutic use; D011905:Genes, ras; D015316:Genetic Therapy; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins; D014162:Transfection
D004274:DNA, Recombinant; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras)