Insulin-like growth factor-1 protects from vascular stenosis and accelerates re-endothelialization in a rat model of carotid artery injury

A. Cittadini, M. G. Monti, M. C. Castiello, E. D'arco, G. Galasso, D. Sorriento, L. Saldamarco, A. De Paulis, R. Napoli, G. Iaccarino, L. Saccà

Research output: Contribution to journalArticle

Abstract

Background: IGF-1 is a potent mitogen for vascular smooth muscle cells, but exerts protective effects on endothelial cells that may trigger antiatherogenic mechanisms. Objectives: This study was designed to test the hypothesis that an IGF-1 excess following arterial injury prevents neointima formation and vascular stenosis. Methods: Rats were subjected to carotid balloon injury and treated with IGF-1 (1.2 mg kg-1 per die) or saline for 10 days. Results: In IGF-1 treated animals, high tissue levels of eNOS, Akt and its phosphorylated form were found, confirming activation of IGF-1-dependent signaling pathways. IGF-1 markedly reduced neointima formation and post-injury arterial stenosis. IGF-1 exerted proliferative and anti-apoptotic effects in the media of injured carotids, but inhibited mitotic activity and induced apoptosis in the neointima. Furthermore, IGF-1 stimulated mobilization of progenitor endothelial cells and re-endothelialization of the injured arteries. L-NAME administration inhibited IGF-1 vasculoprotective effects. Conclusions: IGF-1 attenuates post-injury carotid stenosis by exerting differential effects in the neointima and tunica media with regard to the key components of the response to injury. The data point to a novel role of IGF-1 as a potent vasculoprotective factor.

Original languageEnglish
Pages (from-to)1920-1928
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume7
Issue number11
DOIs
Publication statusPublished - Nov 2009

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Keywords

  • Carotid arteries
  • Endothelium
  • IGF-1
  • Nitric oxide synthase
  • Restenosis

ASJC Scopus subject areas

  • Hematology

Cite this

Cittadini, A., Monti, M. G., Castiello, M. C., D'arco, E., Galasso, G., Sorriento, D., Saldamarco, L., De Paulis, A., Napoli, R., Iaccarino, G., & Saccà, L. (2009). Insulin-like growth factor-1 protects from vascular stenosis and accelerates re-endothelialization in a rat model of carotid artery injury. Journal of Thrombosis and Haemostasis, 7(11), 1920-1928. https://doi.org/10.1111/j.1538-7836.2009.03607.x