Nature Medicine
1, 541 - 545 (1995)
doi:10.1038/nm0695-541
Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivoCiro Indolfi1, 5, Enrico V. Avvedimento2, Antonio Rapacciuolo1, Emilio Di Lorenzo1, Giovanni Esposito1, Eugenio Stabile1, Antonio Feliciello3, Evelina Mele2, Paola Giuliano3, GianLuigi Condorelli4
& Massimo Chiariello1
1Cattedra di Cardiologia, Università degli Studi di Napoli "Federico II", Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Via Pansini 5, 80131 Naples, Italy
2Dipartimento di Medicina Sperimentale Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Via T. Campanella, 88100 Catanzaro, Italy
3Dipartimento di Biologia e Patologia Molecolare e Cellulare, Università degli Studi di Napoli "Federico II", Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Via Pansini 5, 80131 Naples, Italy
4Jefferson Cancer Institute, Bluemle Life Sciences Building, 233 South 50th Street, Philadelphia, Pennsylvania 19107-5541, USA
5Correspondence should be addressed to C.I. 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.
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