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Purpose: Atherosclerosis (AS) is a chronic inflammatory vascular disease and the predominant cause of ischemic stroke (IS). AS is a potential pathogenetic factor in IS. However, the processes by which they interact remain unknown. The purpose of this paper was to investigate the shared gene signatures and putative molecular processes in AS and IS. Methods: Gene Expression Omnibus (GEO) data for AS and IS microarrays were retrieved. The co-expression modules associated with AS and IS were identified using the Weighted Gene Co-Expression Network Analysis (WGCNA). We constructed an interaction network of shared differentially expressed genes in AS and IS and conducted an enrichment analysis using ClueGO software. We validated the results in a separate cohort through differential gene analysis. Additionally, we retrieved AS and IS-related miRNAs from the Human microRNA Disease Database (HMDD) and predicted their target genes using miRWalk. We then built a network of miRNAs-mRNAs-KEGG pathways using the shared genes. Results: Through WGCNA, we identified five modules and six modules as significant in AS and IS, respectively. A ClueGO enrichment analysis of common genes showed that highly active CCR1 chemokine receptor binding is critical to AS and IS pathogenesis. The differential analysis expression results in another cohort closely matched these findings. The miRNA-mRNA network suggested that hsa-miR-330-5p, hsa-miR-143-3p, hsa-miR-16-5p, hsa-miR-152-3p might regulate the shared gene KRAS, which could be a key player in AS and IS. Conclusion: We integrated ischemic stroke and carotid atherosclerosis public database data and found that ATF3, CCL3, CCL4, JUNB, KRAS, and ZC3H12A may affect both, making them novel biomarkers or therapeutic target genes. Clinical samples and expression trends supported our analyses of pivotal genes.
RESUMO
BACKGROUND: The vascular morphology and the characteristics of atherosclerotic plaques in the middle cerebral artery (MCA) have not been fully studied with high-resolution magnetic resonance imaging (HR-MRI). OBJECTIVE: HR-MRI was applied to investigate vascular morphology and atherosclerotic plaque in patients with symptomatic MCA stenosis. MATERIALS AND METHODS: A total of 343 patients with symptomatic MCA stenosis were enrolled in this study. All the patients were examined by HR-MRI to analyze the morphology of MCA and the M1 segment (MCA-M1), the characteristics and the location of the plaques. RESULTS: The proportion of L-shaped MCA-M1 decreased, while the proportion of S-shaped MCAM1 increased with age. The anterior plaques were the most common in all the patients. The superior plaques were relatively common in patients with L-shaped and U-shaped MCA-M1, while the inferior plaques were relatively common in patients with inverted U-shaped and S-shaped MCAM1. Among all the plaques, the majority were isointense or heterogeneous. The MCA-M1 morphology had no direct relationship with the common risk factors of atherosclerosis and the clinical outcomes of the patients after 12 months of follow up. CONCLUSION: The morphology of MCA-M1 is not directly related to the plaque burden or the degree of stenosis in patients with symptomatic MCA stenosis. The morphology of MCA-M1 is not associated with the risk factors of atherosclerosis, or the clinical outcomes of the patients.
