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Abstract: SA-PO787

Cardiac Radiation Exposure and Coronary Atherosclerosis: An Inflammatory Interplay

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Nepali, Prerna R., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Mathieu, Mickael, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Monette, Sebastien, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Qiu, Yunping, Albert Einstein College of Medicine, Bronx, New York, United States
  • Kurland, Irwin J., Albert Einstein College of Medicine, Bronx, New York, United States
  • Rimner, Andreas, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Haimovitz-Friedman, Adriana, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background

Cardiac radiation exposure is a known risk factor for the increased cardiovascular mortality observed in cancer patients receiving thoracic radiation therapy (RT). A better understanding of the mechanisms involved is essential to develop preventive and treatment strategies. In this study we hypothesize that the development of accelerated atherosclerosis after RT is dependent upon inflammatory mechanisms that include the activation of eicosanoid pathways.

Methods

Male Apolipoprotein E knockout mice on a high fat diet received 16Gy cardiac RT to the whole or partial (apical or basal) regions of the heart at 9 or 16 weeks (w) of age. Atherosclerotic lesions (H&E) and inflammatory infiltrates (IHC) were assessed 8w post RT. Eicosanoid profile was studied (liquid chromatography mass spectrometry) in the serum of 16w old mice 24 hours post radiation. RNAscope was used to assess LOX mRNA expression post RT.

Results

(1) At 8w follow up, mice receiving basal RT at 16w showed a greater number of atherosclerotic lesions in the basal coronary arteries (29.33 ± 5.48 versus 9 ± 2.70) and basal subendocardial vasculature (6.66 ± 2.07 versus 0.2 ± 0.2) as compared to controls. Inflammatory cells (CD45, CD3) and endothelial adhesion molecules were differentially expressed based upon the site of RT. (2) Protective oxidized EPA metabolites (5HEPE and 12HEPE) were decreased after whole RT but increased after basal irradiation compared to whole RT (Table). (3) 12LOX mRNA was significantly elevated in the cardiac lesions of mice after apical RT and there was a trend towards increased 15LOX and 5LOX mRNA expression post whole, basal and apical RT compared to controls.

Conclusion

Our results indicate that RT to different regions of the heart results in a distinctive variance in the systemic production of eicosanoids and vascular LOX mRNA expression profile which may mediate or be a compensatory response in the development of accelerated atherosclerosis after RT.