J. Vasc. Biol. 42, Sup:2 (2005) p122

P350 Inflammatory response and apoptosis induction after vascular brachytherapy: role of the peroxynitrite-poly(ADP-ribose) polymerase pathway.
1C.J.Beller, 2E.Horvath, 1J.Kosse, 1L.Seres, 1T.Radovits, 3R.Krempien, 4I.Berger, 1S.Hagl, 2C.Szabó, 1G.Szabó
1Department of Cardiac Surgery, University of Heidelberg, Heidelberg, DE; 2Department of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, HU; 3Department of Clinical Radiology, University of Heidelberg, Heidelberg, DE; 4Department of Pathology, University of Heidelberg, Heidelberg, DE.

Objective: We investigated in a surgical rat model of vascular injury the potential role of the peroxynitrite - poly(ADP-ribose)polymerase pathway in inflammatory response and apoptosis induction after surgical vessel reconstruction with consecutive irradiation.

Methods: Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n=10) or were irradiated with 15 Gray (n=13) or 20 Gray (n=10) postoperatively and compared with sham-operated rats (n=10).

Results: After 21 days, neointima formation was significantly suppressed after irradiation. However a significant inflammation of the vessel wall with focal wall necrosis was detected. Immunohistochemistry showed significant staining for nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor in the neointima of the control group. In the irradiated groups these stainings were significantly higher in the media and adventitia compared to the non-irradiated groups.

Conclusions: Activation of the peroxynitrite - poly(ADP-ribose)polymerase pathway was demonstrated, in conjunction with the inflammatory response and apoptosis induction after surgical vessel reconstruction with consecutive irradiation. We propose that poly(ADP-ribose)polymerase may be a new target to prevent restenosis after surgical vessel reconstruction and may be able to ameliorate irradiation induced side-effects of vascular brachytherapy.

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