Tenascin-C作为阿霉素诱导的心肌病免疫组织病理学的潜在标志物。

European heart journal open Pub Date : 2023-10-09 eCollection Date: 2023-09-01 DOI:10.1093/ehjopen/oead104
Tatsuya Nishikawa, Mikio Shiba, Yoshihiko Ikeda, Keiko Ohta-Ogo, Takumi Kondo, Tomoka Tabata, Toru Oka, Wataru Shioyama, Hironori Yamamoto, Taku Yasui, Yoshiharu Higuchi, Hatsue Ishibashi-Ueda, Keiichiro Honma, Chisato Izumi, Shuichiro Higo, Kinta Hatakeyama, Yasushi Sakata, Masashi Fujita
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摘要

目的:阿霉素用于几种癌症类型的经典化疗。阿霉素诱导的心肌病(DOX-CM)是癌症患者的一个关键问题。然而,将DOX-CM的诊断与其他心肌病的诊断区分开来是困难的。因此,在本研究中,我们旨在确定诊断DOX-CM的新的组织病理学特征。方法和结果:包括在两个医疗中心接受心脏组织病理学检查的12名连续的DOX-CM患者。12名扩张型心肌病患者组成对照组,他们在年龄、性别和左心室射血分数方面与DOX-CM患者相匹配。另一个对照组包括连续5例由酪氨酸激酶抑制剂或血管内皮生长因子抑制剂诱导的癌症治疗相关心功能不全患者作为对照。评估tenascin-C的阳性面积、浸润巨噬细胞的数量以及p62和泛素阳性心肌细胞的存在。人诱导多能干细胞来源的心肌细胞(hiPSC CMs)用于体外研究。与对照组相比,DOX-CM组心肌的腱蛋白阳性面积和巨噬细胞数量显著增加(P<0.01)。腱蛋白阳性区域与CD68和CD163阳性细胞的数量相关(分别为r=0.748和r=0.656)。p62免疫染色在10例(83%)DOX-CM患者中呈阳性。此外,蛋白质印迹分析显示,阿霉素治疗后,hiPSC CMs中tenascin-C水平显著升高(P<0.05)。结论:结合组织病理学评估tenascin-C、巨噬细胞和p62/泛素可作为诊断DOX-CM的新工具。阿霉素可能直接影响心肌中tenascin-C的表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Tenascin-C as a potential marker for immunohistopathology of doxorubicin-induced cardiomyopathy.

Aims: Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM.

Methods and results: Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for in vitro investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (P < 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (r = 0.748 and r = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (P < 0.05).

Conclusion: The combined histopathological assessment for tenascin-C, macrophages, and p62/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.

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