Abstract 3069: Radiation exposure of the base of the heart accelerates coronary atherosclerosis

Abstract

Abstract Purpose: To determine the mechanisms associated with the development of atherosclerotic lesions in different areas of the heart exposed to radiation therapy (RT). We hypothesize that accelerated development of cardiovascular disease (CVD) post-RT is dependent upon the differential sensitivity of regions of the heart to radiation. Experimental procedures: Male Apolipoprotein E knockout (ApoE-/-) mice on a high fat diet received 16Gy cardiac irradiation targeted to the whole or partial (apical or basal) region of the heart at 9 weeks or 16 weeks of age. Atherosclerotic lesions and inflammatory changes in the hearts as compared to control unirradiated mice were assessed eight weeks following radiation. Results: Our studies demonstrate that atherosclerotic lesion formation is accelerated by cardiac RT. Our results show that (1) Subendocardial atherosclerotic lesions at the base of heart of 9 weeks old mice after basal irradiation are comparable to those formed post whole heart irradiation. (2) A greater number of atherosclerotic lesions were present in the basal coronary arteries and basal subendocardial vasculature after irradiating the cardiac base as compared to unirradiated controls in older mice at 8 weeks post-RT. (3) Apical or whole heart irradiation had no impact on the development or acceleration of lesions in the basal region of the hearts of 16 week old mice, thus demonstrating the adverse impact of basal irradiation. (4) Infiltration of inflammatory cells (CD45 and CD3) and enhanced expression of endothelial adhesion molecules (CD31) were differentially and locally regulated based upon the site of irradiation. This also demonstrates a long-term inflammatory response to RT which may be crucial in the development of RT-related CVD. Conclusion: Our results indicate that the base of the heart is more prone to development of RT-induced atherosclerotic lesions that could lead to CVD and thus omitting this area from RT direct exposure may improve the quality of life for cancer patients receiving thoracic RT. Citation Format: Prerna R. Nepali, Mickael Mathieu, Sarah Kitz, Chiharuko Nakauchi, James Russell, Sebastien Monette, Andreas Rimner, Fiona A. Stewart, Edgar A. Jaimes, Adriana Haimovitz-Friedman. Radiation exposure of the base of the heart accelerates coronary atherosclerosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3069.