Search

Background: Ischemic Stroke (IS) is a serious cerebrovascular disease, which leads to irreversible damage or death of brain cells. Effective control of stroke risk factors can effectively reduce the incidence of IS. However, there was an “obesity paradox” about the relationship between obesity and the prognosis of IS, in which obesity would not bring worse outcomes than non-obese IS patients. Objective: Herein, we aimed to investigate the transcriptional response to IS in obese and nonobese mice brain via RNA-Seq technology. The datasets of obese and non-obese mice with/without IS were obtained from the Gene Expression Omnibus (GEO) database. Methods: Differentially expressed genes (DEGs) between Control and Obesity (DEGsObesity) and between Obesity and Obese-Stroke (DEGsObese-Stroke) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Protein-Protein Interaction (PPI) network analysis were performed to predict the function of DEGs. 28 and 109 DEGs were screened in DEGsObesity and DEGsObese-Stroke, respectively. Results: Significantly, in the top 10 key-genes of DEGsObese-Stroke (Tnf, Lgals3, Serpinb2, Ly6c2, Chil3, Clec4e, Mmp3, Mefv, Spn, Tlr8), Tnf and Mefv were involved in the NOD-like receptor signaling pathway, which was consistent with KEGG pathway enrichment results. And Chil3, as a mononuclear cell marker, was significantly elevated in Obese-Stroke compared with Stroke, suggesting mononuclear cell, rather than other peripheral immune cells, infiltrated into the brain of Obese-stroke. Conclusion: Hence, we concluded that obesity could affect the brain microenvironment at the transcriptome level and Stroke after obesity could lead to more changes in NOD-like receptor signaling pathway and monocyte infiltration, compared with non-obese Stroke.

Background: Recent studies have reported that the levels of serum interleukin-33 (IL- 33) and its receptor, suppression of tumorigenicity 2 (ST2), are potential biomarkers for susceptibility of cardiovascular diseases. However, the genetic association of the IL-33/ST2 axis with cardiovascular diseases remains controversial. Objective: We aimed to investigate the association between common variants in the IL-33/ST2 axis and ischemic stroke in the Han Chinese population. Methods: We consecutively enrolled 1166 patients with ischemic stroke and 1079 age- and gender- matched controls. Eight single nucleotide polymorphisms (SNPs) within IL-33/ST2 axis were genotyped using the improved Multiple Ligase Detection Reaction platform. We analyzed the association between the tested SNPs and ischemic stroke at both the genotype and haplotype levels. Results: Binary logistic regression analysis indicated that rs10435816 (additive model: odds ratio [OR]=0.72, 95% confidence interval [CI], 0.54-0.95; recessive model: OR=0.72, 95%CI, 0.56- 0.94) was associated with a decreased risk of ischemic stroke after adjustment of confounding factors. Subgroup analysis indicated that rs10435816 (additive model: OR=0.61, 95%CI, 0.41-0.89; recessive model: OR=0.56, 95%CI, 0.40-0.80), rs7025417 (additive model: OR=0.57, 95%CI, 0.39-0.83), rs11792633 (additive model: OR=0.66, 95%CI, 0.46-0.95; recessive model: OR=0.67, 95%CI, 0.49-0.93), and rs7044343 (additive model: OR=0.69, 95%CI, 0.48-0.97; recessive model: OR=0.67, 95%CI, 0.49-0.91) were associated with a decreased risk of large-artery atherosclerosis stroke after adjustment of confounding factors. Conclusion: Our findings suggested an association between common variants in the IL-33/ST2 axis and a decreased risk of ischemic stroke in the Han Chinese population.