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复发性自发性颈内动脉夹层的细胞外基质蛋白特征。

Extracellular matrix protein signature of recurrent spontaneous cervical artery dissection.

机构信息

From the Departments of Neurology (L.M., R.P., C.B., T.T., J.W., S.K., M.K.), Neuroradiology (E.R.G.), Internal Medicine IV (P.P.), and Dermatology (G.R.), Medical University Innsbruck, Austria; King's British Heart Foundation Centre (J.B.-B., M.L., X.Y., M.M.), King's College London, London, UK; and VASCage (S.K.), Research Centre on Vascular Ageing and Stroke, Innsbruck, Austria.

出版信息

Neurology. 2020 Oct 13;95(15):e2047-e2055. doi: 10.1212/WNL.0000000000010710. Epub 2020 Sep 4.

Abstract

OBJECTIVE

To assess whether connective tissue disorder is evident in patients with spontaneous cervical artery dissection and therefore identify patients at risk of recurrence using a cutting-edge quantitative proteomics approach.

METHODS

In the ReSect study, all patients with spontaneous cervical artery dissection treated at the Innsbruck University Hospital since 1996 were invited to attend a standardized clinical follow-up examination. Protein abundance in skin punch biopsies (n = 50) was evaluated by a cutting-edge quantitative proteomics approach (liquid chromatography-mass spectrometry) that has hitherto not been applied to such patients.

RESULTS

Patients with 1-time single-vessel (n = 19) or multiple-vessel (n = 13) dissections did not differ between each other or compared to healthy controls (n = 12) in protein composition. Patients with recurrent spontaneous cervical artery dissection (n = 6), however, showed significantly different expression of 25 proteins compared to the other groups combined. Literature review and Gene Ontology term annotation check revealed that 13 of the differently expressed proteins play a major role in the structural integrity of connective tissue or are linked to connective tissue disorders. These proteins showed clustering to a collagen/elastin cluster and one consisting of desmosome related proteins.

CONCLUSION

This study unravels an extracellular matrix protein signature of recurrent spontaneous cervical artery dissection. In the long run and after large-scale validation, our findings may well assist in identifying patients at risk of recurrent spontaneous cervical artery dissection and thus guide therapy.

摘要

目的

评估结缔组织疾病是否在自发性颈内动脉夹层患者中表现明显,并采用先进的定量蛋白质组学方法确定易复发患者。

方法

在 ReSect 研究中,邀请自 1996 年以来在因斯布鲁克大学医院接受自发性颈内动脉夹层治疗的所有患者参加标准化临床随访检查。通过先进的定量蛋白质组学方法(液相色谱-质谱法)评估皮肤穿刺活检(n = 50)中的蛋白质丰度,该方法迄今尚未应用于此类患者。

结果

单次单血管(n = 19)或多血管(n = 13)夹层患者与健康对照组(n = 12)之间在蛋白质组成上无差异。然而,复发性自发性颈内动脉夹层(n = 6)患者与其他两组相比,25 种蛋白的表达明显不同。文献综述和基因本体术语注释检查显示,13 种差异表达的蛋白在结缔组织的结构完整性中起主要作用,或与结缔组织疾病有关。这些蛋白聚类为胶原/弹性蛋白簇和一个由桥粒相关蛋白组成的簇。

结论

本研究揭示了复发性自发性颈内动脉夹层的细胞外基质蛋白特征。从长远来看,经过大规模验证后,我们的研究结果很可能有助于识别易复发自发性颈内动脉夹层的患者,并指导治疗。

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