Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice.

Autor: Hoving S; Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Heeneman S, Gijbels MJ, te Poele JA, Pol JF, Gabriels K, Russell NS, Daemen MJ, Stewart FA
Jazyk: angličtina
Zdroj: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2011 Oct; Vol. 101 (1), pp. 100-8. Date of Electronic Publication: 2011 Oct 14.
DOI: 10.1016/j.radonc.2011.09.019
Abstrakt: Background and Purpose: We previously showed that irradiating the carotid arteries of ApoE(-/-) mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis.
Material and Methods: ApoE(-/-) mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L(-/-)/ApoE(-/-) and ApoE(-/-) littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks.
Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis.
Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.
(Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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