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Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms
BACKGROUND: Rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. Our previous study revealed a downregulation of genes related to T lymphocytes and an upregulation of genes related to monocytes and neutrophils after IA rupture. It remains...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498486/ https://www.ncbi.nlm.nih.gov/pubmed/31046777 http://dx.doi.org/10.1186/s12967-019-1891-6 |
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author | Korostynski, Michal Piechota, Marcin Morga, Rafal Hoinkis, Dzesika Golda, Slawomir Zygmunt, Magdalena Dziedzic, Tomasz Moskala, Marek Slowik, Agnieszka Pera, Joanna |
author_facet | Korostynski, Michal Piechota, Marcin Morga, Rafal Hoinkis, Dzesika Golda, Slawomir Zygmunt, Magdalena Dziedzic, Tomasz Moskala, Marek Slowik, Agnieszka Pera, Joanna |
author_sort | Korostynski, Michal |
collection | PubMed |
description | BACKGROUND: Rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. Our previous study revealed a downregulation of genes related to T lymphocytes and an upregulation of genes related to monocytes and neutrophils after IA rupture. It remains unknown whether that resulted from alterations in transcription or cell count. We sought to characterize the systemic response to IA rupture through analysis of transcript expression profiles in peripheral blood cells. We also investigated effects of IA rupture on the composition of mononuclear cells in peripheral blood. METHODS: We included 19 patients in the acute phase of IA rupture (RAA, first 72 h), 20 patients in the chronic phase (RAC, 3–15 months), and 20 controls. Using deep transcriptome sequencing, we analyzed the expression of protein-coding and noncoding RNAs. Expression levels, transcript biotypes, alternative splicing and other features of the regulated transcripts were studied. A functional analysis was performed to determine overrepresented ontological groups among gene expression profiles. Flow cytometry was used to analyze alterations in the level of mononuclear leukocyte subpopulations. RESULTS: Comparing RAA and controls, we identified 491 differentially expressed transcripts (303 were downregulated, and 188 were upregulated in RAA). The results indicate that the molecular changes in response to IA rupture occur at the level of individual transcripts. Functional analysis revealed that the most impacted biological processes are related to regulation of lymphocyte activation and toll-like receptor signaling pathway. Differences between RAC and controls were less prominent. Analysis of leukocyte subsets revealed a significantly decreased number of CD4+ lymphocytes and increase of classical and intermediate monocytes in RAA patients compared to controls. CONCLUSIONS: IA rupture in the acute phase strongly influences the transcription profiles of peripheral blood cells as well as the composition of mononuclear cells. A specific pattern of gene expression alteration was found, suggesting a depression of lymphocyte response and enhancement of monocyte activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1891-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6498486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64984862019-05-09 Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms Korostynski, Michal Piechota, Marcin Morga, Rafal Hoinkis, Dzesika Golda, Slawomir Zygmunt, Magdalena Dziedzic, Tomasz Moskala, Marek Slowik, Agnieszka Pera, Joanna J Transl Med Research BACKGROUND: Rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. Our previous study revealed a downregulation of genes related to T lymphocytes and an upregulation of genes related to monocytes and neutrophils after IA rupture. It remains unknown whether that resulted from alterations in transcription or cell count. We sought to characterize the systemic response to IA rupture through analysis of transcript expression profiles in peripheral blood cells. We also investigated effects of IA rupture on the composition of mononuclear cells in peripheral blood. METHODS: We included 19 patients in the acute phase of IA rupture (RAA, first 72 h), 20 patients in the chronic phase (RAC, 3–15 months), and 20 controls. Using deep transcriptome sequencing, we analyzed the expression of protein-coding and noncoding RNAs. Expression levels, transcript biotypes, alternative splicing and other features of the regulated transcripts were studied. A functional analysis was performed to determine overrepresented ontological groups among gene expression profiles. Flow cytometry was used to analyze alterations in the level of mononuclear leukocyte subpopulations. RESULTS: Comparing RAA and controls, we identified 491 differentially expressed transcripts (303 were downregulated, and 188 were upregulated in RAA). The results indicate that the molecular changes in response to IA rupture occur at the level of individual transcripts. Functional analysis revealed that the most impacted biological processes are related to regulation of lymphocyte activation and toll-like receptor signaling pathway. Differences between RAC and controls were less prominent. Analysis of leukocyte subsets revealed a significantly decreased number of CD4+ lymphocytes and increase of classical and intermediate monocytes in RAA patients compared to controls. CONCLUSIONS: IA rupture in the acute phase strongly influences the transcription profiles of peripheral blood cells as well as the composition of mononuclear cells. A specific pattern of gene expression alteration was found, suggesting a depression of lymphocyte response and enhancement of monocyte activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1891-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-02 /pmc/articles/PMC6498486/ /pubmed/31046777 http://dx.doi.org/10.1186/s12967-019-1891-6 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Korostynski, Michal Piechota, Marcin Morga, Rafal Hoinkis, Dzesika Golda, Slawomir Zygmunt, Magdalena Dziedzic, Tomasz Moskala, Marek Slowik, Agnieszka Pera, Joanna Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
title | Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
title_full | Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
title_fullStr | Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
title_full_unstemmed | Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
title_short | Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
title_sort | systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498486/ https://www.ncbi.nlm.nih.gov/pubmed/31046777 http://dx.doi.org/10.1186/s12967-019-1891-6 |
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