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      Altered expression of microRNAs in the myocardium of rats with acute myocardial infarction

      research-article
      1 , 2 , 3 , 1 , 3 , 3 , 4 , , 1 , 3 ,
      BMC Cardiovascular Disorders
      BioMed Central

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          Abstract

          Background

          MicroRNAs(miRNAs) are important cellular components and their dysfunction is associated with various diseases. Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases. Although several miRNAs are reported to be associated with AMI, more novel miRNAs are needed to further investigate and improve certainty

          Methods

          We applied a well-established acute myocardial infarction rat model and performed miRNAs microarray experiments upon the myocardium tissue of rats with AMI and under sham control. We identified the differentially expressed miRNAs and analyzed the function of miRNA targets, transcription factors, and host genes based on bioinformatics.

          Results

          As a result, the levels of expression of seventeen miRNAs significantly deregulated, of which four miRNAs were further validated by qRT-PCR. In addition, we observed that the transcription factors, targets, and host genes of these deregulated miRNAs are enriched in cardiovascular-related functions.

          Conclusion

          We found that the miRNAs expression level altered in rats with AMI and differentially expressed miRNAs may be novel biomarkers of AMI.

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          Most cited references17

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          In silico prediction of protein-protein interactions in human macrophages

          Background: Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results: We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion: Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.
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            Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis.

            Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied by a pathological remodeling response that includes hypertrophic cardiac growth and fibrosis, which impair cardiac contractility. Previously, we showed that cardiac hypertrophy and heart failure are accompanied by characteristic changes in the expression of a collection of specific microRNAs (miRNAs), which act as negative regulators of gene expression. Here, we show that MI in mice and humans also results in the dysregulation of specific miRNAs, which are similar to but distinct from those involved in hypertrophy and heart failure. Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.
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              Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.

              MicroRNAs (miRNAs) are short endogenous RNAs known to post-transcriptionally repress gene expression in animals and plants. A microarray profiling survey revealed the expression patterns of 175 human miRNAs across 24 different human organs. Our results show that proximal pairs of miRNAs are generally coexpressed. In addition, an abrupt transition in the correlation between pairs of expressed miRNAs occurs at a distance of 50 kb, implying that miRNAs separated by <50 kb typically derive from a common transcript. Some microRNAs are within the introns of host genes. Intronic miRNAs are usually coordinately expressed with their host gene mRNA, implying that they also generally derive from a common transcript, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic miRNAs.
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                Author and article information

                Journal
                BMC Cardiovasc Disord
                BMC Cardiovascular Disorders
                BioMed Central
                1471-2261
                2010
                1 March 2010
                : 10
                : 11
                Affiliations
                [1 ]Department of Cardiology, Peking University Third Hospital, Beijing, China
                [2 ]Department of Cardiology, Beijing Military General Hospital, Beijing, China
                [3 ]MOE key Laboratory of Molecular Cardiology, Peking University, Beijing, China
                [4 ]Department of Biomedical Informatics, Peking University Health Science Center, Beijing, China
                Article
                1471-2261-10-11
                10.1186/1471-2261-10-11
                2844352
                20187981
                c26b9aa9-5394-419b-955a-3a5c92e5924a
                Copyright ©2010 Shi et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 October 2009
                : 1 March 2010
                Categories
                Research article

                Cardiovascular Medicine
                Cardiovascular Medicine

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