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心脏转甲状腺素蛋白淀粉样变性血清的蛋白质组学分析:生物标志物发现的诊断和预后意义

Proteomic Analysis of Serum in Cardiac Transthyretin Amyloidosis: Diagnostic and Prognostic Implications for Biomarker Discovery.

作者信息

Waś Joanna, Gawor-Prokopczyk Monika, Sioma Agnieszka, Szewczyk Rafał, Pel Aleksandra, Krzysztoń-Russjan Jolanta, Niedolistek Magdalena, Sokołowska Dorota, Grzybowski Jacek, Mazurkiewicz Łukasz

机构信息

Department of Medical Biology, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland.

Department of Cardiomyopathy, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland.

出版信息

Biomedicines. 2025 Jul 6;13(7):1647. doi: 10.3390/biomedicines13071647.

Abstract

Having serum biomarkers available for cardiac transthyretin amyloidosis (ATTR-CA) would be beneficial for diagnosis and prognosis. This study aimed to identify potential ATTR-CA biomarkers through proteomic analysis. Serum proteomic analyses were conducted on 15 ATTR-CA patients before receiving treatment, 11 ATTR-CA patients who had received tafamidis treatment for at least six months, and 13 patients with suspected cardiac amyloidosis who were later ruled out. All patients underwent blood tests, standard 12-lead electrocardiography, transthoracic echocardiography, and Tc-DPD scintigraphy. Proteomic analysis revealed significant differences in protein levels among the study groups. Key findings revealed increased levels of several proteins, including ceruloplasmin, apolipoprotein E, SERPINA1, and cDNA FLJ54111 (which is highly similar to serum transferrin), in ATTR-CA patients before receiving specific treatment. There was also a reduction in prothrombin, transferrin, CD14, and alpha-2-macroglobulin. In the ATTR-CA group treated with tafamidis, elevated levels of SERPINA1, paraoxonase 1, and complement C2 were observed. Notably, levels of cDNA FLJ54111 and SERPINA3 were reduced in this group. Compared to the control group, patients with ATTR-CA exhibited higher levels of ceruloplasmin, SERPINA3, and VCAM1, as well as lower levels of ApoA-I, ApoA-II, clusterin, and gelsolin. Controls exhibited elevated levels of transthyretin and prothrombin. This study identified candidate serum biomarkers for diagnosing ATTR-CA and monitoring the effectiveness of tafamidis treatment.

摘要

拥有可用于心脏转甲状腺素蛋白淀粉样变性(ATTR-CA)的血清生物标志物将有助于诊断和预后评估。本研究旨在通过蛋白质组学分析确定潜在的ATTR-CA生物标志物。对15例接受治疗前的ATTR-CA患者、11例接受氯苯唑酸治疗至少6个月的ATTR-CA患者以及13例后来被排除疑似心脏淀粉样变性的患者进行了血清蛋白质组分析。所有患者均接受了血液检查、标准12导联心电图、经胸超声心动图和锝-二膦酸盐闪烁扫描。蛋白质组分析显示研究组之间蛋白质水平存在显著差异。主要发现显示,在接受特定治疗前的ATTR-CA患者中,几种蛋白质水平升高,包括铜蓝蛋白、载脂蛋白E、丝氨酸蛋白酶抑制剂A1(SERPINA1)和cDNA FLJ54111(与血清转铁蛋白高度相似)。凝血酶原、转铁蛋白、CD14和α-2-巨球蛋白也有所减少。在接受氯苯唑酸治疗的ATTR-CA组中,观察到SERPINA1、对氧磷酶1和补体C2水平升高。值得注意的是,该组中cDNA FLJ54111和丝氨酸蛋白酶抑制剂A3(SERPINA3)水平降低。与对照组相比,ATTR-CA患者的铜蓝蛋白、SERPINA3和血管细胞黏附分子1(VCAM1)水平较高,而载脂蛋白A-I、载脂蛋白A-II、簇集素和凝溶胶蛋白水平较低。对照组的转甲状腺素蛋白和凝血酶原水平升高。本研究确定了用于诊断ATTR-CA和监测氯苯唑酸治疗效果的候选血清生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff85/12293033/dc3c8583174c/biomedicines-13-01647-g001.jpg

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