Seemann Ingar, Te Poele Johannes A M, Hoving Saske, Stewart Fiona A
Division of Biological Stress Response (H3), The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
ISRN Cardiol. 2014 Mar 27;2014:506348. doi: 10.1155/2014/506348. eCollection 2014.
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.
背景。放射疗法常用于治疗乳腺癌和胸段癌，但它也会导致微血管延迟损伤并增加心脏死亡风险。内皮细胞增殖和血管再形成对于修复微血管损伤及维持受照射心脏的功能至关重要。因此，我们研究了骨髓源性内皮祖细胞（BM来源的EPCs）修复辐射诱导的微血管损伤的潜力。材料与方法。对成年C57BL/6小鼠的心脏给予16 Gy辐射。在照射后16周和28周，给小鼠注射从Eng(+/+)或Eng(+/-)小鼠获得的BM来源的EPCs。相对于仅接受辐射的小鼠和年龄匹配的对照小鼠，在移植后40周评估移植小鼠的形态学损伤。结果。心脏照射降低了微血管密度，并增加了存活毛细血管中的内皮损伤（碱性磷酸酶表达降低，血管性血友病因子增加）。用BM来源的EPCs治疗并未减轻微血管损伤。然而，来自Eng(+/+)和Eng(+/-)小鼠的BM来源的EPCs均减少了辐射诱导的胶原蛋白沉积。结论。用BM来源的EPCs治疗并未修复辐射诱导的微血管损伤，但确实抑制了纤维化。内皮糖蛋白缺乏并未损害这一过程。
