Systemic Transcriptional Alterations of Innate and Adaptive Immune Signaling Pathways in Atherosclerosis, Ischemia Stroke, and Myocardial Infarction
- *Corresponding Author:
- Chiang-Ching Huang
Joseph J. Zilber School of Public Health
University of Wisconsin, Milwaukee
1240 N. 10th Street Milwaukee
Wisconsin 53201-0413, USA
Tel: +414 227-5006
E-mail: [email protected]
Received Date: December 29, 2014; Accepted Date: March 30, 2015; Published Date: April 03, 2015
Citation: Barr TL, VanGilder RL, Seiberg R, Petrone A, Chantler PD, et al. (2015) Systemic Transcriptional Alterations of Innate and Adaptive Immune Signaling Pathways in Atherosclerosis, Ischemia Stroke, and Myocardial Infarction. J Bioanal Biomed 7: 029-034. doi: 10.4172/1948-593X.1000120
Copyright: © 2015 Barr TL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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. Methods and 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). Conclusion: 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.