Anthracycline chemotherapy-mediated vascular dysfunction as a model of accelerated vascular aging.
Anthracycline chemotherapy-mediated vascular dysfunction as a model of accelerated vascular aging.
复制标题
蒽环类药物化疗介导的血管功能障碍作为加速血管老化的模型。
DOI：
10.1002/aac2.12033
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Seals DR
中科院分区：
文献类型：
--
作者：
Clayton ZS;Hutton DA;Mahoney SA;Seals DR
心血管疾病（CVD）是世界范围内导致死亡的主要原因，而年龄是迄今为止罹患CVD的最大危险因素。血管功能障碍，包括内皮功能障碍和动脉硬化，是心血管疾病风险随年龄增加的主要原因。与衰老相关的血管功能障碍的一个关键机制是氧化应激，氧化应激降低了一氧化氮（NO）的生物利用度，诱导了动脉壁细胞外基质的不利变化（例如，弹性蛋白断裂/降解，胶原沉积）和晚期糖基化终产物的增加，这些终产物在动脉壁结构蛋白中形成交联。尽管血管功能障碍和心血管疾病在老年人中最为普遍，但在任何年龄，一些情况都可能“加速”这些事件的发生。其中一个因素是用蒽环类药物，如阿霉素（DOXO）进行化疗，以对抗常见形式的癌症。与年龄匹配的健康对照相比，接受这些化疗药物治疗的儿童、青少年和年轻人表现出血管功能受损，未来心血管疾病发展的风险增加。蒽环类药物治疗还会加重中年（50-64岁）和老年人（65岁及以上）的血管功能障碍，与年龄匹配的对照组相比，内皮功能障碍和动脉僵硬更严重。总的来说，这些观察结果表明，蒽环类化疗药物的使用诱导血管衰老样表型，后者有助于暴露于这些药物的癌症幸存者过早心血管疾病。在这里，我们回顾了支持这些观点的现有文献，讨论了可能保护动脉免受这些不利影响的潜在机制和干预措施，确定了研究空白，并为未来的研究提出了建议。
Cardiovascular diseases (CVD) are the leading cause of death worldwide, and age is by far the greatest risk factor for developing CVD. Vascular dysfunction, including endothelial dysfunction and arterial stiffening, is responsible for much of the increase in CVD risk with aging. A key mechanism involved in vascular dysfunction with aging is oxidative stress, which reduces the bioavailability of nitric oxide (NO) and induces adverse changes to the extracellular matrix of the arterial wall (e.g., elastin fragmentation/degradation, collagen deposition) and an increase in advanced glycation end products, which form crosslinks in arterial wall structural proteins. Although vascular dysfunction and CVD are most prevalent in older adults, several conditions can “accelerate” these events at any age. One such factor is chemotherapy with anthracyclines, such as doxorubicin (DOXO), to combat common forms of cancer. Children, adolescents and young adults treated with these chemotherapeutic agents demonstrate impaired vascular function and an increased risk of future CVD development compared with healthy age-matched controls. Anthracycline treatment also worsens vascular dysfunction in mid-life (50-64 years of age) and older (65 and older) adults such that endothelial dysfunction and arterial stiffness are greater compared to age-matched controls. Collectively, these observations indicate that use of anthracycline chemotherapeutic agents induce a vascular aging-like phenotype and that the latter contributes to premature CVD in cancer survivors exposed to these agents. Here, we review the existing literature supporting these ideas, discuss potential mechanisms as well as interventions that may protect arteries from these adverse effects, identify research gaps and make recommendations for future research.