Dataset Information

Serum-based proteomics reveals lipid metabolic and immunoregulatory 、dysregulation in cervical artery dissection with stroke

ABSTRACT: Cervical artery dissection (CAD) is an important causal factor for stroke in young and middle-aged individuals and presents a great burden to the individual stroke victim. However, the pathophysiological mechanisms underlying CAD remain unknown. Here, an isobaric tagging for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed, to identify differentially expressed proteins in serum samples obtained from spontaneous CAD and non-CAD ischemic stroke subjects. Differential protein expression was analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway over-representation, and six differential proteins were selected for enzyme-linked immunosorbent assay (ELISA) validation. Through KEGG analysis, the significantly differentiated proteins were primarily involved in immunoregulation, blood coagulation, and lipid metabolism. For the first time, differential expressions of apolipoprotein B (APOB), apolipoprotein C-I (APOC-I), lipopolysaccharide-binding protein (LBP), vascular cell adhesion molecule 1(VCAM1), fibulin-1 (FBLN1), and ficolin-2 (FCN2) were confirmed as being significantly upregulated in CAD as compared to non-CAD ischemic stroke subjects. In conclusion, proteomic analysis reveals that early perturbation of immunoregulation and lipid metabolism may be involved in the pathophysiology of CAD. Specifically, the panel of six proteins identified are promising as serum-based predictors for the detection of increased CAD risk in stroke subjects.

ORGANISM(S): Homo Sapiens

SUBMITTER: Zhenhua Zhou

PROVIDER: PXD017340 | iProX | Thu Jan 30 00:00:00 GMT 2020

REPOSITORIES: iProX

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Publications

Serum-Based Proteomics Reveals Lipid Metabolic and Immunoregulatory Dysregulation in Cervical Artery Dissection With Stroke.

Yang Yongtao Y Peng Jing J Wang Suxia S Huang Jialu J Ran Hong H Chen Kangning K Zhou Zhenhua Z

Frontiers in neurology 20200519

Cervical artery dissection (CAD) is an important causal factor for stroke in young and middle-aged individuals and presents a great burden to the individual stroke victim. However, the pathophysiological mechanisms underlying CAD remain unknown. Here, an iTRAQ (isobaric tagging for relative and absolute quantitation)-based quantitative proteomic approach was performed, to identify differentially expressed proteins in serum samples obtained from spontaneous CAD and non-CAD ischemic stroke subject ...[more]

PMID: 32508734

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Project description:Objective Acute ischemic stroke is a group of diseases characterized by high morbidity, high disability, high mortality, and high recurrence, and most patients are left with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a major cause of acute ischemic stroke pathogenesis, and its formation and progression are influenced by a combination of pathways including lipid metabolism and inflammatory response. sICAS has a high risk of clinical recurrence. Therefore, timely and effective assessment of intracranial vascular stenosis in acute ischemic stroke is particularly important for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence.Method The aim of this study was to screen for unique differential proteins that are closely associated with sICAS in patients with acute ischemic stroke. Fourteen patients with acute ischemic stroke were included and divided into stenosis and control groups according to whether the intracranial vessels were stenosed or not. First, mass spectrometry was applied to all patients included using 4D Label-free proteome quantification technology to obtain the differential proteins between the two groups. Secondly, functional enrichment analysis using GO classification, KEGG pathway, Domain and other bioinformatics libraries were used to obtain differential protein-related enrichment trends. Then, the STRING (v.11.5) protein interaction network database was applied for comparison to obtain the differential protein interactions and corresponding target proteins. Finally, PRM was applied to validate the selected target proteins.Result 1096 proteins were obtained by mass spectrometry, of which the number of quantitatively comparable proteins was 991. When P value<0.05, a change in differential expression of more than 1.3 was used as the change threshold for significant up-regulation and less than 1/1.3 was used as the change threshold for significant down-regulation, resulting in a total of 46 differential proteins screened, of which 24 proteins were significantly up-regulated and 22 proteins were significantly down-regulated. In PRM experiments, five proteins involved in lipid metabolism and inflammatory response have been validated, namely A2M ,LBP, CTSG,CST3,FABP1.Conclusion By detecting the changes of these five proteins in acute ischemic stroke patients, we can provide a basis for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence, and also help to promote the development of drugs for the prevention of acute ischemic stroke recurrence by combining Chinese and Western medicine.

Dataset Information

Serum-based proteomics reveals lipid metabolic and immunoregulatory 、dysregulation in cervical artery dissection with stroke

Publications

Serum-Based Proteomics Reveals Lipid Metabolic and Immunoregulatory Dysregulation in Cervical Artery Dissection With Stroke.

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