Background. Radiotherapy is commonly used to treat breast and thoracic cancers but it also causes delayed microvascular damage and increases the risk of cardiac mortality. Endothelial cell proliferation and revascularization are crucial to restore microvasculature damage and maintain function of the irradiated heart. We have therefore examined the potential of bone marrow-derived endothelial progenitor cells (BM-derived EPCs) for restoration of radiation-induced microvascular damage. Material & Methods. 16？Gy was delivered to the heart of adult C57BL/6 mice. Mice were injected with BM-derived EPCs, obtained from Eng+/+ or Eng+/？ mice, 16 weeks and 28 weeks after irradiation. Morphological damage was evaluated at 40 weeks in transplanted mice, relative to radiation only and age-matched controls. Results. Cardiac irradiation decreased microvascular density and increased endothelial damage in surviving capillaries (decrease alkaline phosphatase expression and increased von Willebrand factor). Microvascular damage was not diminished by treatment with BM-derived EPCs. However, BM-derived EPCs from both Eng+/+ and Eng+/？ mice diminished radiation-induced collagen deposition. Conclusion. Treatment with BM-derived EPCs did not restore radiation-induced microvascular damage but it did inhibit fibrosis. Endoglin deficiency did not impair this process. 1. Introduction Radiotherapy is commonly used for treatment of thoracic and chest wall tumors. Although radiotherapy is effective against the cancer, it is also known to induce delayed damage in surrounded normal tissue, including cardiac damage [1–4]. Nowadays, the volume of the heart exposed to radiation is kept as low as possible but for most left sided breast cancer patients the heart still receives a treatment dose of 1 to 5？Gy and this can eventually lead to ischemic heart disease [2, 5–8]. Preclinical studies have demonstrated the involvement of radiation-induced microvascular damage in the development of cardiac injury. Radiation leads to endothelial cell loss, which results in a decrease in microvascular density. Radiation also activates thrombotic and inflammatory reactions in the remaining vessels and induces the development of fibrosis in the myocardium [9–12]. Perfusion defects, measured with single photon emission computerized tomography (SPECT), have been identified in asymptomatic breast cancer patients 6 to 18 months after radiotherapy. The incidence of perfusion defects is much higher for patients with left sided cancer (71%), where radiation dose to the heart is higher, than for right sided cancer
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