Project description:The goal of our study is to uncover the pathogenesis of large-artery atherosclerotic ischemic stroke (LAAIS) and small-artery occlusion ischemic stroke (SAOIS) and analyze their difference using RNA sequencing.RNA sequencing was used to filtrate differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in LAAIS and SAOIS. Specific DEmRNAs and DElncRNAs in LAAIS and SAOIS were further foun. Functional annotation and DElncRNA-DEmRNA co-expression network was built to reveal biological function of DEmRNAs.
Project description:We compared gene expression profiles between asymptomatic and symptomatic atherosclerotic plaques from the same patient. This was accomplished by analyzing carotid plaques from four patients with bilateral high-grade carotid artery stenoses one being symptomatic (TIA or stroke) and the other asymptomatic.
Project description:A microarray analysis of advanced human atherosclerotic carotid artery plaques (equal or over 70% stenosis, NASCET criteria) from radiologically confirmed ipsilateral stroke patients (stroke-susceptible plaques, n=12) compared with carotid plaques collected from clinically asymptomatic patients with clear brain imaging (asymptomatic plaques, n=9) with equivalent conventional risk factors and severity of carotid stenosis.
Project description:Paraoxonase 1 (PON 1) binds to high-density lipoprotein (HDL) and is responsible for its anti-atherosclerotic effect through its antioxidant activity. This dataset contains gene expression data obtained from a study investigating the effects of human paraoxonase 1 treatment on acute ischemic stroke model mice. The study aimed to identify gene expression changes associated with the treatment and to understand the molecular mechanisms underlying the therapeutic effects of human paraoxonase 1 in acute ischemic stroke model mice. The dataset includes raw microarray data and associated metadata. The study was conducted using a middle cerebral artery (MCA) ischemia/reperfusion model in mice, and gene expression was measured in the brain tissue samples collected from control and treated mice. The dataset also includes information on the experimental design, sample collection, and data processing methods used in the study.
Project description:A single nucleotide polymorphism (SNP) in the human glucocorticoid receptor (GR), N363S, has been the focus of several clinical studies, and some epidemiological data link this SNP to increased glucocorticoid sensitivity, coronary artery disease and increased body mass index (BMI). However, molecular studies in vitro using reporter gene expression systems have failed to define a link between this polymorphism and altered glucocorticoid receptor function. To address the biological relevancy of N363S in glucocorticoid receptor mechanisms and function, we established stable U-2 OS (human osteosarcoma) cell lines expressing wild type hGR or N363S using a tetracycline-regulated expression system. Functional assays with reporter gene systems revealed only minor differences between the wild type hGR and N363S receptors under a variety of conditions that probe for GR function. However, examination of this polymorphism by human gene microarray analysis showed, for the first time, that there are significant differences between wild type hGR and the N363S SNP in their ability to selectively regulate gene expression. Several of these genes may define the link between the N363S SNP and human disease. Keywords: human glucocorticoid receptor, N363S single nucleotide polymorphism, microarray gene analysis
Project description:A single nucleotide missense polymorphism (rs1800449, R158Q) in the propeptide domain of lysyl oxidase (LOX-PP) is associated with increased risk of coronary disease independent of plasma lipid levels. Although the enzymatic function of LOX has an essential role for the cross-linking of extracellular matrix proteins in connective tissues, whether and how LOX-PP R158Q contributes to the development of atherosclerosis has not been clearly established. In this study, we characterized atherosclerotic plaque lesions of both human and mouse arteries and found that LOX is mainly expressed by vascular smooth muscle cells (VSMCs). Using complementary mouse models, we provide evidence that the R158Q polymorphism promotes atherosclerosis and induces proliferation of macrophages and VSMCs without altering LOX enzymatic activity. Using single-cell RNA sequencing, we found that the transcriptional program of atherosclerotic plaques from mice harboring R158Q was strongly enriched for proliferation- and calcification-related genes in a regionally distinct manner. Together, these results establish an enzymatically-independent proatherogenic role for the LOX-PP and suggest its potential as a novel therapeutic target.
