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Bioinformatics Approach to Evaluate Differential Gene Expression of M1/M2 Macrophage Phenotypes and Antioxidant Genes in Atherosclerosis

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Abstract

Atherosclerosis is a pro-inflammatory process intrinsically related to systemic redox impairments. Macrophages play a major role on disease development. The specific involvement of classically activated, M1 (pro-inflammatory), or the alternatively activated, M2 (anti-inflammatory), on plaque formation and disease progression are still not established. Thus, based on meta-data analysis of public micro-array datasets, we compared differential gene expression levels of the human antioxidant genes (HAG) and M1/M2 genes between early and advanced human atherosclerotic plaques, and among peripheric macrophages (with or without foam cells induction by oxidized low density lipoprotein, oxLDL) from healthy and atherosclerotic subjects. Two independent datasets, GSE28829 and GSE9874, were selected from gene expression omnibus (http://www.ncbi.nlm.nih.gov/geo/) repository. Functional interactions were obtained with STRING (http://string-db.org/) and Medusa (http://coot.embl.de/medusa/). Statistical analysis was performed with ViaComplex® (http://lief.if.ufrgs.br/pub/biosoftwares/viacomplex/) and gene score enrichment analysis (http://www.broadinstitute.org/gsea/index.jsp). Bootstrap analysis demonstrated that the activity (expression) of HAG and M1 gene sets were significantly increased in advance compared to early atherosclerotic plaque. Increased expressions of HAG, M1, and M2 gene sets were found in peripheric macrophages from atherosclerotic subjects compared to peripheric macrophages from healthy subjects, while only M1 gene set was increased in foam cells from atherosclerotic subjects compared to foam cells from healthy subjects. However, M1 gene set was decreased in foam cells from healthy subjects compared to peripheric macrophages from healthy subjects, while no differences were found in foam cells from atherosclerotic subjects compared to peripheric macrophages from atherosclerotic subjects. Our data suggest that, different to cancer, in atherosclerosis there is no M1 or M2 polarization of macrophages. Actually, M1 and M2 phenotype are equally induced, what is an important aspect to better understand the disease progression, and can help to develop new therapeutic approaches.

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Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Rede Instituto Brasileiro de Neurociência (IBN-Net)—01.06.0842-00 and MCT/CNPq INCT-TM.

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  1. Laboratory of Cellular Biochemistry, Department of Biochemistry, Institute of Health Basic Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos – 2600, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

    Ricardo Fagundes da Rocha, Marco Antônio De Bastiani & Fábio Klamt

  2. National Institutes of Science & Technology – Translational Medicine (INCT-TM), Porto Alegre, Rio Grande do Sul, Brazil

    Ricardo Fagundes da Rocha, Marco Antônio De Bastiani & Fábio Klamt

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  1. Ricardo Fagundes da Rocha
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da Rocha, R.F., De Bastiani, M.A. & Klamt, F. Bioinformatics Approach to Evaluate Differential Gene Expression of M1/M2 Macrophage Phenotypes and Antioxidant Genes in Atherosclerosis. Cell Biochem Biophys 70, 831–839 (2014). https://doi.org/10.1007/s12013-014-9987-3

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