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肌联蛋白中基质金属蛋白酶-12 裂解片段作为心血管血清生物标志物的临床评估。

Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker.

机构信息

Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Herlev, Denmark.

出版信息

J Transl Med. 2012 Jul 6;10:140. doi: 10.1186/1479-5876-10-140.

DOI:10.1186/1479-5876-10-140
PMID:22768802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3487750/
Abstract

BACKGROUND

Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage.

METHODS

A competitive ELISA was developed to specifically measure levels of the titin sequence 12670' NVTVEARLIK 12679', derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa).

RESULTS

Mean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (± 43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (± 90.14)] (P < 0.05). AMI patients showed 56.3% higher levels [792 ng/ml (± 149)] (P < 0.05).

CONCLUSIONS

The titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.

摘要

背景

肌联蛋白是一种存在于心脏和骨骼肌中的肌肉特异性蛋白,负责恢复被动张力。肌联蛋白的水平和功能已被证明受到心脏损伤的影响。由于在临床环境中体内测量肌联蛋白水平固有困难,我们旨在开发一种可靠地测量血清中降解肌联蛋白片段的测定法,并可能用于评估心肌损伤。

方法

开发了一种竞争 ELISA 来特异性测量肌联蛋白序列 12670'NVTVEARLIK 12679 的水平,该序列由基质金属蛋白酶 (MMP)-12 降解肌联蛋白产生。90 名个体的血清样本分为 3 个相等大小的组。一组被诊断为急性心肌梗死 (AMI),而其余两组是无症状个体,要么有 CT 扫描冠状动脉钙的迹象(CT-plusCa),要么没有冠状动脉钙(CT-noCa)。

结果

CT-noCa 组肌联蛋白片段的平均几何水平为 506.5ng/ml(±43.88)。CT-plusCa 组标志物水平高出 50.6%[763ng/ml(±90.14)](P<0.05)。AMI 患者的水平高出 56.3%[792ng/ml(±149)](P<0.05)。

结论

在未确诊和确诊的 CVD 个体中均存在肌联蛋白-12670 片段。AMI 组标志物水平的统计学显著增加表明,这种新表位生物标志物可能是 AMI 的有用血清标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab3/3487750/a17d869929f3/1479-5876-10-140-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab3/3487750/78731d840af6/1479-5876-10-140-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab3/3487750/a17d869929f3/1479-5876-10-140-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab3/3487750/78731d840af6/1479-5876-10-140-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab3/3487750/a17d869929f3/1479-5876-10-140-2.jpg

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