Morbidelli Lucia, Donnini Sandra, Ziche Marina
Department of Life Sciences, University of Siena, Via A. Moro 2, 53100, Siena, Italy.
Cardiooncology. 2016 Mar 15;2(1):3. doi: 10.1186/s40959-016-0010-6.
The vascular endothelium plays a fundamental role in the maintenance of tissue homeostasis, regulating local blood flow and other physiological processes. Chemotherapeutic drugs and target therapies, including antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors, not only efficiently act against tumor growth, but may also induce endothelial dysfunction and cardiovascular toxicity. Continued research efforts aim to better understand, prevent and mitigate these chemotherapy associated cardiovascular diseases. Conventional chemotherapeutic agents, such as anthracyclines, platinum compounds, and taxanes, and newer targeted agents, such as bevacizumab, trastuzumab, and tyrosine kinase inhibitors, have known risk of cardiovascular toxicity, which can limit their effectiveness by promoting increased morbidity and/or mortality. This review describes a) the activity of anticancer agents in inducing endothelial dysfunction, b) the metabolic pathways and signalling cascades which may be targeted by protective agents able to maintain or restore endothelial cell function, such as endothelial nitric oxide synthase/fibroblast growth factor-2 (eNOS-FGF-2) pathway, and c) the drugs/strategies reported to improve endothelial function and to reduce the risks of cardiovascular diseases such as angiotensin converting enzyme inhibitors (ACEi) and beta blockers, that are fundamental therapies in chronic heart failure (HF), as well as non-standard HF treatments such ad nitric oxide donors and antioxidant strategies. There is increasing interest in whether ACEi, beta-blockers, and/or statins might prevent and/or therapeutically control cardiotoxic effects in cancer patients. Maintaining endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor drug-effectiveness, is essential for preserving or recovering cardiovascular homeostasis. In this respect, the early detection and immediate therapy of cardiovascular toxicity appear crucial for substantial recovery of cardiac function in cancer patients.
血管内皮在维持组织稳态、调节局部血流及其他生理过程中发挥着重要作用。化疗药物和靶向治疗药物，包括针对血管内皮生长因子（VEGF）或其受体的抗血管生成药物，不仅能有效对抗肿瘤生长，还可能导致内皮功能障碍和心血管毒性。持续的研究致力于更好地理解、预防和减轻这些与化疗相关的心血管疾病。传统化疗药物，如蒽环类、铂类化合物和紫杉烷类，以及新型靶向药物，如贝伐单抗、曲妥珠单抗和酪氨酸激酶抑制剂，都存在已知的心血管毒性风险，这可能通过增加发病率和/或死亡率来限制其有效性。本综述描述了：a）抗癌药物诱导内皮功能障碍的活性；b）可能被能够维持或恢复内皮细胞功能的保护剂靶向的代谢途径和信号级联反应，如内皮型一氧化氮合酶/成纤维细胞生长因子-2（eNOS-FGF-2）途径；c）据报道可改善内皮功能并降低心血管疾病风险的药物/策略，如血管紧张素转换酶抑制剂（ACEi）和β受体阻滞剂，它们是慢性心力衰竭（HF）的基础治疗药物，以及非标准的HF治疗方法，如一氧化氮供体和抗氧化策略。人们越来越关注ACEi、β受体阻滞剂和/或他汀类药物是否能预防和/或治疗性控制癌症患者的心脏毒性作用。在化疗药物治疗期间或之后维持内皮功能，同时不影响抗肿瘤药物的有效性，对于维持或恢复心血管稳态至关重要。在这方面，心血管毒性的早期检测和即时治疗对于癌症患者心脏功能的实质性恢复似乎至关重要。
