Cathepsin B Dependent Cleavage Product of Serum Amyloid A1 Identifies Patients with Chemotherapy-Related Cardiotoxicity.
Cathepsin B Dependent Cleavage Product of Serum Amyloid A1 Identifies Patients with Chemotherapy-Related Cardiotoxicity.
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血清淀粉样蛋白 A1 的组织蛋白酶 B 依赖性裂解产物可识别患有化疗相关心脏毒性的患者。
DOI：
10.1021/acsptsci.9b00035
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发表时间：
2019
影响因子：
--
通讯作者：
Hu,TonyY
中科院分区：
文献类型：
--
作者：
Zhang,Fangfang;Lyon,ChristopherJ;Walls,RobertJ;Ning,Bo;Fan,Jia;Hu,TonyY
癌症长期生存率的提高导致化疗相关心力衰竭的患病率增加，但治疗诱导的心脏损伤可能要到治疗后很长时间才能检测到。建议监测心脏功能;然而，癌症患者的心血管损伤与原发性心功能不全患者不同，这限制了传统心脏生物标志物的实用性。在此，我们检测了组织蛋白酶B产生的肽的血浆水平，组织蛋白酶B在化疗诱导的心脏损伤过程中释放。我们应用nanotrap分级富集来自接受或不接受化疗的癌症患者的血浆肽。通过质谱鉴定与化疗诱导的心脏毒性相关的肽，而不是其他心脏损伤，并使用酶抑制实验确定其对组织蛋白酶B活性的依赖性。我们发现，一种肽（SAA-1525）来源于血清淀粉样蛋白A1显着增加心脏毒性患者，其生产被抑制时，血浆样品与组织蛋白酶B特异性抑制剂预处理。血浆SAA-1525也与心脏损伤的其他标志物相关。血浆SAA-1525水平的分析可能具有作为监测亚临床损伤的快速和微创方法的潜力，从而允许及时干预以减轻进一步的心脏损伤并避免更严重的临床表现。
Improvements in long-term cancer survival rates have resulted in an increase in the prevalence of chemotherapy-linked cardiac failure, but treatment-induced cardiac injuries may not be detected until long after therapy. Monitoring cardiac function is recommended; however, cardiovascular injury in cancer patients differs from those with primary cardiac dysfunction, which limits the utility of traditional cardiac biomarkers. Here we examined plasma levels of peptides produced by cathepsin B, which is released during chemotherapy-induced cardiac injury. We applied nanotrap fractionation to enrich plasma peptides from cancer patients treated with or without chemotherapy. Peptides associated with chemotherapy-induced cardiotoxicity, but not other cardiac injury, were identified by mass spectrometry, and their dependence on cathepsin B activity was determined using enzyme inhibition experiments. We found that a peptide (SAA-1525) derived from serum amyloid A1 was significantly increased in cardiotoxicity patients, and its production was inhibited when plasma samples were pretreated with cathepsin B specific inhibitors. Plasma SAA-1525 also correlated with other markers of cardiac injury. Analysis of plasma SAA-1525 levels may hold potential as a rapid and minimally invasive method to monitor subclinical injury, thereby allowing timely intervention to mitigate further cardiac damage and avoid more severe clinical presentation.