代谢重构参与肿瘤治疗相关心功能不全机制的研究进展

Mechanisms of Metabolic Remodeling Participating in Cancer Therapy-Related Cardiac Dysfunction

近年随着抗肿瘤药物研发及综合诊治水平提高,肿瘤患者生存质量及生存率明显提高,但绝大部分抗肿瘤药物可直接造成心脏和血管损伤。因此,预防肿瘤治疗相关心血管毒性(CTR-CVT)尤为重要。目前,CTR-CVT包括肿瘤治疗相关心功能不全(CTRCD)、心肌炎、高血压、心律失常、心包疾病等,而CTRCD包括心肌损伤、心肌病及心力衰竭等。研究表明,代谢重构与心血管疾病和肿瘤的发生发展密切相关。基于此,本文主要综述了代谢重构参与CTRCD的机制,并发现能量代谢、氨基酸代谢参与了阿霉素治疗相关心力衰竭的发生,脂肪酸代谢参与了环磷酰胺治疗相关心脏收缩功能障碍及雄激素剥夺疗法治疗相关心血管疾病的发生,线粒体损伤参与了5-氟尿嘧啶治疗相关心脏毒性的发生,线粒体功能障碍和心肌能量代谢改变与曲妥珠单抗治疗相关心功能障碍相关,细胞生物学过程改变可能参与了血管内皮生长因子-酪氨酸激酶抑制剂治疗相关心功能不全的发生,故针对代谢重构进行治疗可能对CTRCD有益。

In recent years,with the development of anti-tumor drugs and the improvement of comprehensive diagnosis and treatment,the quality of life and survival rate of cancer patients have been significantly improved,but almost of anti-tumor drugs can directly cause heart and vascular damage.Therefore,it is particularly important to prevent cancer therapy-related cardiovascular toxicity(CTR-CVT).At present,CTR-CVT includes cancer therapy-related cardiac dysfunction(CTRCD),myocarditis,hypertension,arrhythmia,pericardial disease,etc.,while CTRCD includes myocardial injury,cardiomyopathy and heart failure,etc.Studies have shown that metabolic remodeling is closely related to the occurrence and development of cardiovascular diseases and tumors.Based on this,this article mainly reviews the mechanism of metabolic remodeling participating in CTRCD,and finds that energy metabolism and amino acid metabolism are involved in doxorubicin treatment-related heart failure,fatty acid metabolism is involved in cyclophosphamide treatment-related cardiac systolic dysfunction and androgen deprivation therapy-related cardiovascular disease,mitochondrial damage is involved in 5-fluorouracil treatment-related cardiotoxicity,mitochondrial dysfunction and myocardial energy metabolism changes are associated with trastuzumab treatment-related cardiac dysfunction,changed cellular biological processes is involved in vascular endothelial growth factor-tyrosine kinase inhibitors treatment-related cardiac dysfunction,so the treatment for metabolic remodeling may be beneficial to CTRCD.