P318	Ionizing radiation accelerates the development of atherosclerotic lesions and results in intraplaque hemorrhage in ApoE-/- mice.
1S.Heeneman, 1M.Gijbels, 2H.te Poele, 2J.Kruse, 2N.Russell, 1M.Daemen, 2F.Stewart
1CARIM, Pathology, Maastricht, NL; 2NKI, Experimental Therapy, Amsterdam, NL.

Radiation has been shown to be an independent risk factor in vascular disease after radiotherapy for Hodgkin's disease, breast and neck cancer. The aim of this study was to investigate the development and progression of radiation-induced atherosclerosis. ApoE-/- mice, on a regular chow diet, were given single doses of 14 Gy, or sham treatment (0 Gy) to the neck, including both carotid arteries. At 22 weeks (both male and female mice) and 28 weeks (male mice) after irradiation, blood samples were taken and the aortic tree was removed for histological examination. Markers of systemic inflammation (sICAM-1, sVCAM-1, CRP) as well as cholesterol levels were not different in irradiated versus control animals. At 22 weeks after treatment there was a significant increase in the number of lesions in irradiated versus sham treated carotid arteries of both female mice (4.7±0.3 v 1.8±0.6 lesions/arch, p=0.002) and male mice (3.1±0.4 v 1.7±0.4 lesions/arch, p=0.02). The vast majority of plaques in these irradiated arteries were classified as initial lesions (85% and 96% of total in female and males, respectively). There was no significant increase in the total plaque burden. At the later follow-up time of 28 weeks, male mice showed a borderline increase in the mean size of advanced plaques (irradiated v sham animals, 128733±19393 v 86515±16040 um2, p=0.045), but total plaque burden was not significantly increased. Analysis of “out of field” renal arteries in the female mice, showed that there were no differences with respect to number of plaques or plaque area between irradiated and sham treated mice, respectively. The most marked difference between irradiated and sham carotid arteries was the inflammatory content and signs of intraplaque hemorrhage. The lesions in irradiated arteries were macrophage-rich, with a remarkable influx of inflammatory cells, predominantly granulocytes. Signs of intraplaque hemorrhage (fibrin, macrophages containing erytrocytes and/or iron deposits) were only seen in irradiated arteries and not in age matched controls. We propose that, irradiation accelerates the development of macrophage-rich, inflammatory atherosclerotic lesions, prone to intra-plaque hemorrhage, due to a local vascular specific inflammatory event.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.