Original articleGene expression profiles of cardiomyocytes in rat autoimmune myocarditis by DNA microarray and increase of regenerating gene family
Section snippets
Animals
Lewis rats were obtained from Charles River, Japan (Atsugi, Kanagawa, Japan) and were maintained in our animal facilities until they reached 8 weeks of age. Throughout the studies, all animals were treated in accordance with the guidelines for animal experiments of our institute and the guide for the care and use of laboratory animals published by the U.S. National Institutes of Health.
Induction of experimental autoimmune myocarditis (EAM)
Whole cardiac myosin was prepared from the ventricular muscle of porcine hearts as previously described. It
DNA microarray
Scatter plots of 7711 gene expressions in cardiomyocytes show that the expressions of various genes in cardiomyocytes of EAM markedly increased or decreased compared with normal cardiomyocytes (Fig 1). All data for each spot, which include the Cy3 and Cy5 intensities of which were over 100, are shown in an online data supplement (see online data supplement). Areas surrounded by the triangle in Fig 1 indicate that both Cy3 and Cy5 intensities were over 100, and these intensities showed over
Discussion
In this study, we examined the gene expressions in cardiomyocytes with myocarditis comprehensively. Various comprehensive studies for gene expressions with myocarditis by DNA microarray were reported7, 8, 9; however, other cells except cardiomyocytes (inflammatory cells, fibroblast and smooth muscle cells, and so on) increase in hearts with myocarditis; therefore, gene expressions in cardiomyocytes can be analyzed more accurately using purified cardiomyocytes than unpurified cells. Our
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2014, American Journal of CardiologyCitation Excerpt :PAP was among a group of genes whose expression was restored to normal by eplerenone treatment; this response to eplerenone was associated with improvements in left ventricular remodeling. Watanabe et al5 found that PAP was the most significantly upregulated gene in the hearts of rats with experimental autoimmune myocarditis. Finally, induction of PAP expression can be prevented by chemical inhibitors of stress kinase family proteins in vitro.6
Free heme is a danger signal inducing expression of proinflammatory proteins in cultured cells derived from normal rat hearts
2011, Molecular ImmunologyCitation Excerpt :However, the identity of “danger signals” in myocardium remains largely unknown; nor is it known which resident cells react to these signals and produce pro-inflammatory proteins such as cytokines and chemokines. On the other hand, our previous gene expression analysis in hearts of rats with myocarditis by DNA microarray and real time RT-PCR has demonstrated that gene expression of several iron metabolism-related proteins, such as lipocalin-2/NGAL/alpha-2μ globulin-related protein (Lcn2/NGAL), hepcidin and heme oxygenase-1 (HO-1), is markedly increased in such cardiomyocytes (Ding et al., 2010; Isoda et al., 2010; Watanabe et al., 2008). The role of these proteins in injured hearts still remains largely unknown; however, this finding led us to hypothesize that resident cells in injured hearts are rapidly and strongly influenced by a molecule containing iron, which is critically involved in inflammation.
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Supported in part by a Ministry of Health, Labor, and Welfare in Japan Grant “Research on Regulatory Science of Pharmaceutical and Medical Devices.”