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经无标记蛋白质组学分析慢性心房颤动合并二尖瓣疾病患者的心房纤维化蛋白。

Protein analysis of atrial fibrosis via label-free proteomics in chronic atrial fibrillation patients with mitral valve disease.

机构信息

Cardiovascular Surgery Department, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

出版信息

PLoS One. 2013 Apr 4;8(4):e60210. doi: 10.1371/journal.pone.0060210. Print 2013.

Abstract

BACKGROUND

Atrial fibrosis, as a hallmark of atrial structure remodeling, plays an important role in maintenance of chronic atrial fibrillation, but interrelationship of atrial fibrosis and atrial fibrillation is uncertain. Label-free proteomics can implement high throughput screening for finding and analyzing pivotal proteins related to the disease.. Therefore, we used label-free proteomics to explore and analyze differentially proteins in chronic atrial fibrillation patients with mitral valve disease.

METHODS

Left and right atrial appendages obtained from patients with mitral valve disease were both in chronic atrial fibrillation (CAF, AF≥6 months, n = 6) and in sinus rhythm (SR, n = 6). One part of the sample was used for histological analysis and fibrosis quantification; other part were analyzed by label-free proteomic combining liquid chromatography with mass spectrometry (LC-MS), we utilized bioinformatics analysis to identify differential proteins.

RESULTS

Degree of atrial fibrosis was higher in CAF patients than that of SR patients. 223 differential proteins were detected between two groups. These proteins mainly had vital functions such as cell proliferation, stress response, focal adhesion apoptosis. We evaluated that serine/threonine protein kinase N2 (PKN2), dermatopontin (DP), S100 calcium binding protein B (S100B), protein tyrosine kinase 2 (PTK2) and discoidin domain receptor tyrosine kinase 2 (DDR2) played important roles in fibrotic process related to atrial fibrillation.

CONCLUSION

The study presented differential proteins responsible for atrial fibrosis in chronic atrial fibrillation patients through label-free proteomic analysis. We assessed some vital proteins including their characters and roles. These findings may open up new realm for mechanism research of atrial fibrillation.

摘要

背景

心房纤维化作为心房结构重构的标志,在维持慢性心房颤动中起着重要作用,但心房纤维化与心房颤动的相互关系尚不确定。无标记蛋白质组学可以实现高通量筛选,寻找和分析与疾病相关的关键蛋白。因此,我们使用无标记蛋白质组学方法来探索和分析合并二尖瓣疾病的慢性心房颤动患者的差异蛋白。

方法

从合并二尖瓣疾病的慢性心房颤动(CAF,AF≥6 个月,n=6)和窦性心律(SR,n=6)患者中获取左、右心耳。一部分样本用于组织学分析和纤维化定量;另一部分通过无标记蛋白质组学结合液相色谱-质谱(LC-MS)进行分析,我们利用生物信息学分析来识别差异蛋白。

结果

CAF 患者心房纤维化程度高于 SR 患者。两组之间检测到 223 个差异蛋白。这些蛋白主要具有细胞增殖、应激反应、焦点黏附凋亡等重要功能。我们评估丝氨酸/苏氨酸蛋白激酶 N2(PKN2)、角质蛋白(DP)、S100 钙结合蛋白 B(S100B)、蛋白酪氨酸激酶 2(PTK2)和盘状结构域受体酪氨酸激酶 2(DDR2)在与心房颤动相关的纤维化过程中起着重要作用。

结论

本研究通过无标记蛋白质组学分析,提出了与慢性心房颤动患者心房纤维化相关的差异蛋白。我们评估了一些重要蛋白,包括它们的特征和作用。这些发现可能为心房颤动的机制研究开辟新的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0c5/3617171/ec8e88e12439/pone.0060210.g001.jpg

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