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细胞角蛋白 18 作为肥厚型心肌病患者的新型生物标志物。

Cytokeratin 18 as a Novel Biomarker in Patients with Hypertrophic Cardiomyopathy.

机构信息

Cardiology Department, Heraklion University General Hospital, 71110 Heraklion, Greece.

Cardiology Department, School of Medicine, University of Crete, 71003 Heraklion, Greece.

出版信息

Cells. 2024 Aug 9;13(16):1328. doi: 10.3390/cells13161328.

DOI:10.3390/cells13161328
PMID:39195218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11352956/
Abstract

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease associated with an increased risk for sudden cardiac death (SCD). Cytokeratin 18-based proteins, such as M30 and M65 antigens, are known cell-death biomarkers. M30 antigen is released from cells during apoptosis, and M65 antigen is released during cell death from any cause, such as apoptosis or necrosis. We aimed to study the expression of M30 and M65 antigens in peripheral blood obtained by 46 HCM patients and compare with 27 age- and sex-matched patients without HCM. We also investigated the CK18 expression in myocardium from postmortem HCM hearts. M30 and M65 antigens were significantly increased in the HCM vs. non-HCM group (Μ30: 338 ± 197 U/uL vs. 206 ± 166 U/uL, = 0.003; M65: 428 ± 224 U/uL vs. 246 ± 214 U/uL, = 0.001), and HCM patients with a higher expression of these markers (M30: 417 ± 208 vs. 271 ± 162 U/uL, = 0.011; M65: 518 ± 242 vs. 351 ± 178 U/uL, = 0.011) had a higher risk for SCD. In HCM, both apoptosis and necrosis are increased, but particularly necrosis (M30/M65 ratio: 0.75 ± 0.09 vs. 0.85 ± 0.02, < 0.001). CK18 is expressed in the HCM myocardium (1.767 ± 0.412 vs. 0.537 ± 0.383, % of area, = 0.0058). Therefore, M30 and M65 antigens may be novel biomarkers in HCM.

摘要

肥厚型心肌病(HCM)是一种与心脏性猝死(SCD)风险增加相关的心肌疾病。细胞角蛋白 18 为基础的蛋白,如 M30 和 M65 抗原,是已知的细胞死亡生物标志物。M30 抗原在细胞凋亡过程中从细胞中释放出来,而 M65 抗原在任何原因(如凋亡或坏死)导致的细胞死亡过程中释放。我们旨在研究 46 例 HCM 患者外周血中 M30 和 M65 抗原的表达情况,并与 27 例年龄和性别匹配的无 HCM 患者进行比较。我们还研究了心肌梗死后 HCM 心脏的 CK18 表达。与非 HCM 组相比,HCM 组的 M30 和 M65 抗原明显升高(M30:338±197 U/uL 比 206±166 U/uL, = 0.003;M65:428±224 U/uL 比 246±214 U/uL, = 0.001),且这些标志物表达较高的 HCM 患者(M30:417±208 比 271±162 U/uL, = 0.011;M65:518±242 比 351±178 U/uL, = 0.011)SCD 风险更高。在 HCM 中,凋亡和坏死均增加,但特别是坏死(M30/M65 比值:0.75±0.09 比 0.85±0.02, < 0.001)。CK18 在 HCM 心肌中表达(1.767±0.412 比 0.537±0.383,面积百分比, = 0.0058)。因此,M30 和 M65 抗原可能是 HCM 的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/673a3bbde201/cells-13-01328-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/ae440bcd0432/cells-13-01328-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/ddecedc0d4d2/cells-13-01328-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/a3cf18f1c708/cells-13-01328-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/ce606fcfe66d/cells-13-01328-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/673a3bbde201/cells-13-01328-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/ae440bcd0432/cells-13-01328-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/ddecedc0d4d2/cells-13-01328-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/a3cf18f1c708/cells-13-01328-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/ce606fcfe66d/cells-13-01328-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7812/11352956/673a3bbde201/cells-13-01328-g005.jpg

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本文引用的文献

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Medicine (Baltimore). 2024 Jun 7;103(23):e38342. doi: 10.1097/MD.0000000000038342.
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2023 ESC Guidelines for the management of cardiomyopathies.
2023年欧洲心脏病学会心肌病管理指南。
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Myocardial Histopathology in Patients With Obstructive Hypertrophic Cardiomyopathy.梗阻性肥厚型心肌病患者的心肌组织病理学。
J Am Coll Cardiol. 2021 May 4;77(17):2159-2170. doi: 10.1016/j.jacc.2021.03.008.
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Keratin intermediate filaments in the colon: guardians of epithelial homeostasis.结肠中的角蛋白中间丝:上皮细胞稳态的守护者。
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Usefulness of serum M30 and M65 levels to predict response to neoadjuvant chemotherapy in patients with breast cancer.血清 M30 和 M65 水平对预测乳腺癌患者新辅助化疗反应的作用。
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