Discovery of Cytokines Associated with Large Artery Atherosclerosis Acute Ischemic Stroke by Protein Array Analysis

Abstract

BackgroundThe full comprehension of the Characteristics of acute ischemic stroke (AIS) especially with large artery atherosclerosis remains incomplete. In this study, the differentially expressed proteins and their possible signaling pathways in the patients with LAA-AIS were screened using protein chip and bioinformatics technology.MethodsA total of 54 patients with LAA-AIS were enrolled in the Fourth Medical Centre of Chinese PLA General Hospital from January 2023 to December 2024. Differentially expressed proteins were detected and screened in serum samples from 4 LAA-AIS patients and 4 healthy subjects by RayBiotech cytokine antibody chips. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) analysis were used to screen the features of the differential proteins and involved signaling pathways. The varied concentration of proteins were further validated in 50 LAA-AIS patients and 50 healthy subjects via Enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic(ROC) curves were generated to evaluate the diagnostic value for LAA-AIS.ResultsThe findings shown that three serum proteins displayed considerably different levels in AIS patients compared to healthy individuals, including Vascular cell adhesion molecule-1 (VCAM-1), cardiotrophin-1 (CT-1) and tissue factor pathway inhibitor (TFPI). The levels of VCAM-1, CT-1 increased, while TFPI levels decreased in LAA-AIS patients compared to the healthy control group(P<0.05). The ROC curve analysis results showed that the AUC of VCAM-1 for predicting LAA-AIS was 0.999 (95%CI:0.955, 1.000), the sensitivity and specificity were 98.08% and 100.00%,respectively; the AUC of CT-1 was 0.985 (95%CI:0.930, 0.999), the sensitivity and specificity were 100.00% and 93.33%; the AUC of TFPI 0.792 (95%CI:0.689, 0.874), the sensitivity and specificity were 84.62% and 66.67%,respectively.ConclusionThe enrichment analysis results indicate that differentially expressed proteins were related to inflammation and cytokine pathways. VCAM-1, CT-1 and TFPI may be relevant biomarkers for the diagnosis of acute ischemic stroke caused by large artery atherosclerosis.

Note:
Funding declaration: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of Interests: The authors declare no competing financial interests, including financial and non-financial interests.

Ethical Approval: The study was approved by the Ethics Committee at the Fourth Medical Centre, Chinese PLA General Hospital (Study# 2023KY114-KS001).

Keywords: Acute ischemic stroke, large artery atherosclerosis, Vascular cell adhesion molecule 1, Cardiotrophin-1, Tissue factor pathway inhibitor, Proteomics