Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications

Radiation therapy while important in the management of several diseases, is implicated in the causation of atherosclerosis and other cardiovascular complications. Cancer and atherosclerosis go through the same stages of initiation, promotion, and complication, beginning with a mutation in a single cell. Clinical observations before the 1960s lead to the belief that the heart is relatively resistant to the doses of radiation used in radiotherapy. Subsequently, it was discovered that the heart is sensitive to radiation and many cardiac structures may be damaged by radiation exposure. A significantly higher risk of death due to ischemic heart disease has been reported for patients treated with radiation for Hodgkin's disease and breast cancer. Certain cytokines and growth factors, such as TGF-beta1 and IL-1 beta, may stimulate radiation-induced endothelial proliferation, fibroblast proliferation, collagen deposition, and fibrosis leading to advanced lesions of atherosclerosis. The treatment for radiation-induced ischemic heart disease includes conventional pharmacological therapy, balloon angioplasty, and bypass surgery. Endovascular irradiation has been shown to be effective in reducing restenosis-like response to balloon-catheter injury in animal models. Caution must be exercised when radiation therapy is combined with doxorubicin because there appears to be a synergistic toxic effect on the myocardium. Damage to endothelial cells is a central event in the pathogenesis of damage to the coronary arteries. Certain growth factors that interfere with the apoptotic pathway may provide new therapeutic strategies for reducing the risk of radiation-induced damage to the heart. Exposure to low level occupational or environmental radiation appears to pose no undue risk of atherosclerosis development or cardiovascular mortality. But, other radiation-induced processes such as the bystander effects, abscopal effects, hormesis, and individual variations in radiosensitivity may be important in certain circumstances.