Biomarker study of symptomatic intracranial atherosclerotic stenosis in patients with acute ischemic stroke

Abstract

ObjectiveAcute ischemic stroke (AIS) is characterized by high rates of morbidity, disability, mortality, and recurrence, often leaving patients with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a significant contributor to AIS pathogenesis and recurrence. The formation and progression of sICAS are influenced by pathways such as lipid metabolism and inflammatory response. Given its high risk of clinical recurrence, timely assessment of intracranial vascular stenosis in AIS is crucial for diagnosing sICAS, treating stroke, and preventing stroke recurrence.MethodsFourteen AIS patients were divided into stenosis and control groups based on the presence or absence of intracranial vessel stenosis. Initially, 4D Label-free proteome quantification technology was employed for mass spectrometry analysis to identify differential proteins between the groups. Subsequently, functional enrichment analysis, including GO classification, KEGG pathway, and Domain, revealed trends related to differential proteins. The STRING (v.11.5) protein interaction network database was used to identify differential protein interactions and target proteins. Finally, parallel reaction monitoring (PRM) validated the selected target proteins.ResultsMass spectrometry identified 1,096 proteins, with 991 being quantitatively comparable. Using a p-value <0.05 and differential expression change thresholds of >1.3 for significant up-regulation and < 1/1.3 for significant down-regulation, 46 differential proteins were identified: 24 significantly up-regulated and 22 significantly down-regulated. PRM experiments validated five proteins related to lipid metabolism and inflammatory response: namely alpha-2-macroglobulin (A2M), lipopolysaccharide-binding protein (LBP), cathepsin G (CTSG), cystatin (CST)3, and fatty acid-binding protein (FABP)1.ConclusionThe detection of changes in these five proteins in AIS patients can aid in the diagnosis of sICAS, inform stroke treatment, and assist in preventing stroke recurrence. Moreover, it can contribute to the development of drugs for preventing AIS recurrence by integrating traditional Chinese and Western medicine.