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比较血浆蛋白质组学研究揭示急性主动脉夹层的新型潜在生物标志物。

Comparative Proteomic Investigation of Plasma Reveals Novel Potential Biomarker Groups for Acute Aortic Dissection.

机构信息

The Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang, China.

The Department of Health Care for Cadres, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001 Xinjiang, China.

出版信息

Dis Markers. 2020 Mar 18;2020:4785068. doi: 10.1155/2020/4785068. eCollection 2020.

Abstract

Acute aortic dissection (AAD) is a catastrophic cardiovascular disease with high disability and mortality due to multiple fatal complications. However, the molecular changes of the serum proteome after AAD are not very clear. Here, we performed isobaric tags for relative and absolute quantitation- (iTRAQ-) based comparative proteomic analysis to investigate the proteome profile changes after AAD by collecting plasma samples from 20 AAD patients and 20 controls. Out of the 345 identified proteins, 266 were considered as high-quality quantified proteins (95%confident peptides ≥ 2), of which 25 proteins were accumulated and 12 were reduced in AAD samples. Gene ontology enrichment analysis showed that the 25 AAD-accumulated proteins were enriched in high-density lipoprotein particles for the cellular component category and protein homodimerization acidity for the molecular function category. Protein-protein interaction network analysis showed that serum amyloid A proteins (SAAs), complement component proteins, and carboxypeptidase N catalytic chain proteins (CPNs) possessed the key nodes of the network. The expression levels of six selected AAD-accumulated proteins, B2-GP1, CPN1, F9, LBP, SAA1, and SAA2, were validated by ELISA. Moreover, ROC analysis showed that the AUCs of B2-GP1 and CPN1 were 0.808 and 0.702, respectively. Our data provide insights into molecular change profiles in proteome levels after AAD and indicate that B2-GP1 and CPN1 are potential biomarkers for AAD.

摘要

急性主动脉夹层(AAD)是一种灾难性的心血管疾病,由于多种致命并发症,导致残疾率和死亡率都很高。然而,AAD 后血清蛋白质组的分子变化尚不清楚。在这里,我们通过收集 20 名 AAD 患者和 20 名对照者的血浆样本,进行了相对和绝对定量同位素标记(iTRAQ)-基于比较蛋白质组学分析,以研究 AAD 后的蛋白质组谱变化。在鉴定出的 345 种蛋白质中,有 266 种被认为是高质量定量蛋白质(95%置信肽≥2),其中 25 种在 AAD 样本中积累,12 种减少。基因本体富集分析显示,25 种 AAD 积累蛋白在细胞成分类别中富含高密度脂蛋白颗粒,在分子功能类别中富含蛋白质同源二聚体酸性。蛋白质-蛋白质相互作用网络分析表明,血清淀粉样蛋白 A 蛋白(SAAs)、补体成分蛋白和羧肽酶 N 催化链蛋白(CPNs)具有网络的关键节点。通过 ELISA 验证了 6 种选定的 AAD 积累蛋白,即 B2-GP1、CPN1、F9、LBP、SAA1 和 SAA2 的表达水平。此外,ROC 分析显示 B2-GP1 和 CPN1 的 AUC 分别为 0.808 和 0.702。我们的数据提供了 AAD 后蛋白质组水平分子变化谱的见解,并表明 B2-GP1 和 CPN1 可能是 AAD 的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a5c/7106916/9c8ebcd6658b/DM2020-4785068.001.jpg

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