Zebrafish Models of Cancer Therapy-Induced Cardiovascular Toxicity.
Zebrafish Models of Cancer Therapy-Induced Cardiovascular Toxicity.
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DOI：
10.3390/jcdd8020008
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发表时间：
2021-01-22
影响因子：
2.4
通讯作者：
Asnani A
中科院分区：
文献类型：
--
作者：
Lane S;More LA;Asnani A
综述目的：传统和新型癌症治疗方法都会对患者造成心血管毒性。集成心血管和癌症表型的体内模型允许研究这些药物引起的靶上和靶外毒性机制。斑马鱼是高通量筛选心脏毒性的最佳整体模型，同时评估心脏毒性途径在癌症治疗抗肿瘤效果中的作用。在这里，我们重点介绍了已建立的人类心血管疾病和癌症的斑马鱼模型，斑马鱼在研究癌症治疗相关心血管毒性机制方面的独特优势，以及使用斑马鱼研究毒性时需要考虑的重要限制。最新发现：癌症治疗相关的心血管毒性从传统药物的心肌病到与新的靶向治疗相关的心律失常和血栓并发症。斑马鱼可以用来确定新的治疗策略，在不影响抗肿瘤活性的情况下选择性地保护心脏免受癌症治疗的影响。基因组编辑技术的进步使几个转基因斑马鱼品系的建立成为可能，这些转基因斑马鱼品系对心血管和癌症病理生理学研究有价值。摘要：斑马鱼与人类之间高度的遗传保守性，以及在癌症患者中观察到的心脏毒性表型的重现能力，使斑马鱼成为研究癌症治疗相关心血管毒性的有效模型。尽管该模型比现有的体外和体内模型提供了几个关键的好处，但斑马鱼模型的局限性包括大多数高通量应用所需的早期发育阶段。
Purpose of review: Both traditional and novel cancer therapies can cause cardiovascular toxicity in patients. In vivo models integrating both cardiovascular and cancer phenotypes allow for the study of on- and off-target mechanisms of toxicity arising from these agents. The zebrafish is the optimal whole organism model to screen for cardiotoxicity in a high throughput manner, while simultaneously assessing the role of cardiotoxicity pathways on the cancer therapy’s antitumor effect. Here we highlight established zebrafish models of human cardiovascular disease and cancer, the unique advantages of zebrafish to study mechanisms of cancer therapy-associated cardiovascular toxicity, and finally, important limitations to consider when using the zebrafish to study toxicity. Recent findings: Cancer therapy-associated cardiovascular toxicities range from cardiomyopathy with traditional agents to arrhythmias and thrombotic complications associated with newer targeted therapies. The zebrafish can be used to identify novel therapeutic strategies that selectively protect the heart from cancer therapy without affecting antitumor activity. Advances in genome editing technology have enabled the creation of several transgenic zebrafish lines valuable to the study of cardiovascular and cancer pathophysiology. Summary: The high degree of genetic conservation between zebrafish and humans, as well as the ability to recapitulate cardiotoxic phenotypes observed in patients with cancer, make the zebrafish an effective model to study cancer therapy-associated cardiovascular toxicity. Though this model provides several key benefits over existing in vitro and in vivo models, limitations of the zebrafish model include the early developmental stage required for most high-throughput applications.
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影响因子：
20.1
作者：
Ding Y;Sun X;Huang W;Hoage T;Redfield M;Kushwaha S;Sivasubbu S;Lin X;Ekker S;Xu X
通讯作者：
Xu X
影响因子：
45.3
作者：
Armstrong, Gregory T.;Kawashima, Toana;Oeffinger, Kevin C.
通讯作者：
Oeffinger, Kevin C.
脊椎动物心脏传导系统的遗传和生理解剖。
影响因子：
9.8
作者：
Chi NC;Shaw RM;Jungblut B;Huisken J;Ferrer T;Arnaout R;Scott I;Beis D;Xiao T;Baier H;Jan LY;Tristani-Firouzi M;Stainier DY
通讯作者：
Stainier DY
影响因子：
30.8
作者：
Gerull, B;Gramlich, M;Thierfelder, L
通讯作者：
Thierfelder, L
影响因子：
37.8
作者：
Cardinale, Daniela;Colombo, Alessandro;Cipolla, Carlo M.
通讯作者：
Cipolla, Carlo M.