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

Yongtao Yang,Jialu Huang,Kangning Chen,Zhenhua Zhou,Suxia Wang,Jing Peng,Hong Ran

doi:10.3389/fneur.2020.00352

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 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 subjects. Differential protein expression was analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway overrepresentation, and six differential proteins were selected for enzyme-linked immunosorbent assay 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, apolipoprotein C-I, lipopolysaccharide-binding protein, vascular cell adhesion molecule 1, fibulin-1, and ficolin-2 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 is promising as serum-based biomarkers for the detection of increased CAD risk in stroke subjects.

Highlights

Cervical artery dissection (CAD) is an important cause of cerebral ischemia in young and middle-aged patients
The present study demonstrated for the first time significantly increased levels of lipopolysaccharide-binding protein (LBP) in CAD compared to non-CAD ischemic stroke subjects, which were consistent with infection and inflammation as an important risk factor causing a transient arteriopathy linked to spontaneous CAD [19]
130 differentially expressed proteins were found in serum sampled from CAD and non-CAD ischemic stroke subjects using an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach

Summary

Introduction

Cervical artery dissection (CAD) is an important cause of cerebral ischemia in young and middle-aged patients. Accounting for only 2% of all ischemic strokes, CAD accounts for 8–25% of strokes in patients younger than 45 years [1]. Such a high incidence of stroke presents a great burden to the individual stroke victim and to their family, society, and the economy [2]. A lack of clinical symptoms associated with CAD is regarded as the main cause of missed diagnoses. Biomarkers of Stroke in Cervical Artery Dissection recognized in the past few years as involved in at least some aspects of this disease. The underlying pathogenesis responsible for spontaneous CAD is unknown, making the diagnosis of CAD more challenging

Methods

Results

Discussion

Conclusion