American Journal of Immunology

Microarray Analysis of Human Vascular Smooth Muscle Cell Responses to Bacterial Lipopolysaccharide

Joe Minta James, J. Yun, Sandy Der and Shikha Rana

DOI : 10.3844/ajisp.2007.56.73

American Journal of Immunology

Volume 3, Issue 2

Pages 56-73

Abstract

Accumulating evidence suggest a causal role of bacterial and viral infections in atherogenesis. Bacterial lipopolysaccharide (LPS) has been shown to stimulate resting vascular smooth muscle cells (SMC) with the production of inflammatory cytokines and modulation of quiescent cells to the proliferative and synthetic phenotype. To comprehensively identify biologically important genes associated with LPS-induced SMC phenotype modulation, we compared the transcriptomes of quiescent human coronary artery SMC and cells treated with LPS for 4 and 22 h. The SMCs responded robustly to LPS treatment by the differential regulation of several genes involved in chromatin remodeling, transcription regulation, translation, signal transduction, metabolism, host defense, cell proliferation, apoptosis, matrix formation, adhesion and motility and suggest that the induction of clusters of genes involved in cell proliferation, migration and ECM production may be the main force that drives the LPS-induced phenotypic modulation of SMC rather than the differential expression of a single gene or a few genes. An interesting observation was the early and dramatic induction of four tightly clustered interferon-induced genes with tetratricopeptide repeats (IFIT1, 2, 4, 5). siRNA knock-down of IFIT1 in SMC was found to be associated with a remarkable up-regulation of TP53, CDKN1A and FOS, suggesting that IFIT1 may play a role in cell proliferation. Our data provide a comprehensive list of genes involved in LPS biology and underscore the important role of LPS in SMC activation and phenotype modulation which is a pivotal event in the onset of atherogenesis.

Copyright

© 2007 Joe Minta James, J. Yun, Sandy Der and Shikha Rana. 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.