ABSTRACT

Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly prominent among patients receiving mediastinal radiotherapy, such as breast cancer and Hodgkin’s lymphoma patients. A number of mechanisms of radiation-induced CVD pathogenesis have been proposed such as endothelial inflammatory activation, premature endothelial senescence, increased ROS and mitochondrial dysfunction. However, current research seems to point to a so-far unexamined and potentially novel involvement of epigenetics in radiation-induced CVD pathogenesis. Firstly, epigenetic mechanisms have been implicated in CVD pathophysiology. In addition, several studies have shown that ionizing radiation can cause epigenetic modifications, especially DNA methylation alterations. As a result, this review aims to provide a summary of the current literature linking DNA methylation to radiation-induced CVD and thereby explore DNA methylation as a possible contributor to radiation-induced CVD pathogenesis.

摘要

癌症治疗中的放射疗法涉及使用电离辐射杀死癌细胞。尽管放射治疗已显示出对癌症复发和死亡率的显着改善，但已记录了一些放射引起的不良反应。在这些不良反应中，放射诱发的心血管疾病（CVD）在接受纵隔放射治疗的患者中尤为突出，例如乳腺癌和霍奇金淋巴瘤患者。已经提出了辐射诱导的CVD发病机制的许多机制，例如内皮炎症激活、内皮过早衰老、ROS增加和线粒体功能障碍。然而，目前的研究似乎指出，表观遗传学在辐射诱发的 CVD 发病机制中的作用尚未得到检验，而且可能是新颖的。首先，表观遗传机制与CVD病理生理学有关。此外，多项研究表明电离辐射可引起表观遗传修饰，尤其是 DNA 甲基化改变。因此，本综述旨在总结当前将 DNA 甲基化与辐射诱发的 CVD 联系起来的文献，从而探讨 DNA 甲基化作为辐射诱发的 CVD 发病机制的可能因素。