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

@article{citeulike:2961518, 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-18Ralpha/beta 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-gamma, IL-6, and IL-8 mRNA expression and nuclear factor-kappaB 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.}, address = {Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. pamaffia@unina.it}, author = {Maffia, P. and Grassia, G. and Di Meglio, P. and Carnuccio, R. and Berrino, L. and Garside, P. and Ianaro, A. and Ialenti, A. }, citeulike-article-id = {2961518}, doi = {http://dx.doi.org/10.1161/CIRCULATIONAHA.105.602714}, issn = {1524-4539}, journal = {Circulation}, keywords = {atherosclerosis, cardiovascular-disease, il-18}, month = {August}, number = {5}, pages = {430--437}, posted-at = {2008-07-04 01:12:28}, priority = {2}, title = {Neutralization of interleukin-18 inhibits neointimal formation in a rat model of vascular injury.}, url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.105.602714}, volume = {114}, year = {2006} }

TY - JOUR ID - citeulike:2961518 L3 - citeulike-article-id:2961518 TI - Neutralization of interleukin-18 inhibits neointimal formation in a rat model of vascular injury. JF - Circulation VL - 114 IS - 5 SP - 430 EP - 437 AD - Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. pamaffia@unina.it SN - 1524-4539 N2 - 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-18Ralpha/beta 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-gamma, IL-6, and IL-8 mRNA expression and nuclear factor-kappaB 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. KW - atherosclerosis KW - cardiovascular-disease KW - il-18 AU - Maffia, P AU - Grassia, G AU - Di Meglio, P AU - Carnuccio, R AU - Berrino, L AU - Garside, P AU - Ianaro, A AU - Ialenti, A PY - 2006/08/01/ UR - http://dx.doi.org/10.1161/CIRCULATIONAHA.105.602714 ER -