Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury

Ciro Indolfi, Enrico Vittorio Avvedimento, Emilio Di Lorenzo, Giovanni Esposito, Antonio Rapacciuolo, Paola Giuliano, Domenico Grieco, Luigi Cavuto, Angela M. Stingone, Ilaria Ciullo, Gianluigi Condorelli, Massimo Chiariello

Research output: Contribution to journalArticle

Abstract

Injury of the arterial wall induces the formation of the neointima. This structure is generated by the growth of mitogenically activated smooth muscle cells of the arterial wall. The molecular mechanism underlying the formation of the neointima involves deregulated cell growth, primarily triggered by the injury of the arterial wall. The activated gene products transmitting the injury-induced mitogenic stimuli have been identified and inhibited by several means: transdominant negative expression vectors, antisense oligodeoxynucleotides, adenovirus-mediated gene transfer, antibodies and inactivating drugs. Results of our study show that local administration of 3',5'-cyclic AMP and phosphodiesterase-inhibitor drugs (aminophylline and amrinone) to rats markedly inhibits neointima formation after balloon injury in vivo and in smooth muscle cells in vitro. The growth inhibitory effect of aminophylline was completely reversed by the inhibition of cAMP-dependent protein kinase A (PKA). These findings indicate an alternative approach to the treatment of diseases associated with injury-induced cell growth of the arterial wall, as stimulation of cAMP signaling is pharmacologically feasible in the clinical setting.

Original languageEnglish
Pages (from-to)775-781
Number of pages7
JournalNature Medicine
Volume3
Issue number7
DOIs
Publication statusPublished - Jul 1997

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Indolfi, C., Avvedimento, E. V., Di Lorenzo, E., Esposito, G., Rapacciuolo, A., Giuliano, P., Grieco, D., Cavuto, L., Stingone, A. M., Ciullo, I., Condorelli, G., & Chiariello, M. (1997). Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury. Nature Medicine, 3(7), 775-781. https://doi.org/10.1038/nm0797-775