Bioinformatics‐based analysis of mechanistic differences in vascular endothelial injury ischemic stroke induced by atrial fibrillation and atherosclerosis

Abstract

Studies of the intracranial vasculature in patients with ischemic stroke caused by atherosclerosis (AS) and cardiac embolism have revealed significantly different degrees of AS, plaque, and vascular stenosis. And the endothelium has a great influence on the vasculature throughout the circulatory system, especially in the brain. This study aimed to investigate the mechanistic differences in endothelial injury between atrial fibrillation (AF)-and AS-induced ischemic stroke. All target genes of AF, AS, and the vascular endothelial cell (VC) were obtained from the GeneCards database; the differential genes of AF and AS separately associated with the VC were established by a Venn diagram. A protein-protein interaction network was created, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to perform genomic enrichment and functional enrichment analysis. Hub genes were selected by Maximal Clique Centrality algorithm ranking and correlation linkage in the STRING database, and then, clinical serum samples were used to verify the quantitative expressions in the AF, AF stroke, AS, and AS stroke groups. Fifty-five AF-VCrelated genes and ninety-three AS-VC-related genes were screened, which differed in biological function, cellular composition, and molecular function. The genes correlation between AF and vascular endothelial cells (VCs) was KRAS and PTPN11, and those correlation between AS and VCs was IL-4, IFNG, IL-17A, and CSF-2. IL-4 and CSF-2 may be relevant proteins involved in the differences in stroke mechanisms between AF and AS, and they may act by further influencing the function of their downstream cells.This study provides a preliminary theoretical basis for investigating the differences in mechanisms of endothelial injury between AF-and AS-induced ischemic stroke.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies

“…IGFBP-2 was mainly observed in cardiomyocytes and endothelial and mesothelial cells. Taking in consideration that the endothelial expression of adhesion molecules, chemotactic agents, and growth factors results in higher thrombogenicity of the atrium [40], and that IGFPB-2 has been related to angiogenesis [18], vascular permeability, and transendothelial migration processes [18,31], we performed in vitro experiments to determine the effect of IGFBP-2 neutralization on endothelial function. IGFBP-2 neutralization almost significantly diminished the transendothelial migration of monocytes and significantly decreased microvascular permeability that could contribute to reduced thrombo-inflammation and thrombogenicity.…”