title: Systemic Transcriptional Alterations of Innate and Adaptive Immune Signaling Pathways in Atherosclerosis, Ischemia Stroke, and Myocardial Infarction.
abstract: BACKGROUND
  Transcriptional profiles are available for a variety of cardiovascular-related diseases. The goal of this study was to compare blood transcriptional profiles of the Toll-like receptor (TLR), T-cell receptor (TCR), and B-cell receptor (BCR) signaling pathways in asymptomatic atherosclerosis, acute ischemic stroke, and myocardial infarction patients to identify common mechanisms of immune regulation and their association with epigenetic regulation.
  
  
  RESULTS
  Peripheral blood gene expression profiles from human atherosclerosis-related diseases and healthy controls were downloaded from Gene Expression Omnibus (GEO). Genes in the TLR, TCR, and BCR pathways were retrieved from the NCBI BioSystems database. Significance of gene enrichment and concordance of expression changes in each pathway was compared between studies. Gene expression was significantly correlated across the three disease conditions (p<10-15) and the proportion of significant genes was high (30~60%, p<0.001). Hub genes identified by weighted gene co-expression network analysis (WGCNA) in the TCR/BCR sub-network, including CD81 and TCR-CD3ζ, were significantly down-regulated and highly correlated with DNA (cytosine-5-)-methyltransferase 1 (DNMT1).
  
  
  CONCLUSIONS
  Common biologically relevant networks associated with immune regulation in stroke, atherosclerosis, and myocardial infarction were discovered. Given the high correlation of DNMT1 with these immune signaling pathways, epigenetic regulation may contribute to the coordination of innate and adaptive immune response in all CVD disease states. Down-regulation of the TCR-BCR axis in the adaptive immune system offers critical information for the investigation of the functional mechanisms underlying chronic inflammation-induced immune suppression in cardiovascular disease and stroke.
authors.affiliation: Department of Health Restoration School of Nursing and Center for Basic and Translational Stroke Research West Virginia University, USA.
authors.forename: Taura L
authors.initials: TL
authors.lastname: Barr
authors.affiliation: Department of Health Restoration West Virginia University School of Nursing and Emergency Medicine, USA.
authors.forename: Reynal L
authors.initials: RL
authors.lastname: VanGilder
authors.affiliation: Feinberg School of Medicine, Northwestern University, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Seiberg
authors.affiliation: School of Medicine, Center for Neuroscience West Virginia University, USA.
authors.forename: Ashely
authors.initials: A
authors.lastname: Petrone
authors.affiliation: Division of Exercise Physiology and Center for Cardiovascular and Respiratory Sciences, School of Medicine, West Virginia University, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Chantler
authors.affiliation: Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, USA.
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
keywords: Atherosclerosis; Gene expression; Immune system; Stroke