Neutralization of interleukin-18 inhibits neointimal formation in a rat model of vascular injury

Maffia, P. , Grassia, G., Di Meglio, P., Carnuccio, R., Berrino, L., Garside, P. , Ianaro, A. and Ialenti, A. (2006) Neutralization of interleukin-18 inhibits neointimal formation in a rat model of vascular injury. Circulation, 114, pp. 430-437. (doi:10.1161/CIRCULATIONAHA.105.602714) (PMID:16864728)

Maffia, P. , Grassia, G., Di Meglio, P., Carnuccio, R., Berrino, L., Garside, P. , Ianaro, A. and Ialenti, A. (2006) Neutralization of interleukin-18 inhibits neointimal formation in a rat model of vascular injury. Circulation, 114, pp. 430-437. (doi:10.1161/CIRCULATIONAHA.105.602714) (PMID:16864728)

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Abstract

Background— Studies in humans and animal models suggest that interleukin-18 (IL-18) plays a crucial role in vascular pathologies. IL-18 is a predictor of cardiovascular death in angina and is involved in atherotic plaque destabilization. Higher IL-18 plasma levels also are associated with restenosis after coronary artery angioplasty performed in patients with acute myocardial infarction. We investigated the effective role of IL-18 in neointimal formation in a balloon-induced rat model of vascular injury. Methods and Results— Endothelial denudation of the left carotid artery was performed by use of a balloon embolectomy catheter. Increased expression of IL-18 and IL-18Rα/β mRNA was detectable in carotid arteries from days 2 to 14 after angioplasty. The active form of IL-18 was highly expressed in injured arteries. Strong immunoreactivity for IL-18 was detected in the medial smooth muscle cells at days 2 and 7 after balloon injury and in proliferating/migrating smooth muscle cells in neointima at day 14. Moreover, serum concentrations of IL-18 were significantly higher among rats subjected to vascular injury. Treatment with neutralizing rabbit anti-rat IL-18 immunoglobulin G significantly reduced neointimal formation (by 27%; P<0.01), reduced the number of proliferating cells, and inhibited interferon-γ, IL-6, and IL-8 mRNA expression and nuclear factor-κB activation in injured arteries. In addition, in vitro data show that IL-18 affects smooth muscle cell proliferation. Conclusions— These results identify a critical role for IL-18 in neointimal formation in a rat model of vascular injury and suggest a potential role for IL-18 neutralization in the reduction of neointimal development.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale and Garside, Professor Paul and Grassia, Dr Gianluca
Authors: Maffia, P., Grassia, G., Di Meglio, P., Carnuccio, R., Berrino, L., Garside, P., Ianaro, A., and Ialenti, A.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:24 July 2006

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