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Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis
Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045661/ https://www.ncbi.nlm.nih.gov/pubmed/30006564 http://dx.doi.org/10.1038/s41598-018-29026-0 |
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author | Vajen, Tanja Koenen, Rory R. Werner, Isabella Staudt, Mareike Projahn, Delia Curaj, Adelina Sönmez, Tolga Taha Simsekyilmaz, Sakine Schumacher, David Möllmann, Julia Hackeng, Tilman M. Hundelshausen, Philipp von Weber, Christian Liehn, Elisa A. |
author_facet | Vajen, Tanja Koenen, Rory R. Werner, Isabella Staudt, Mareike Projahn, Delia Curaj, Adelina Sönmez, Tolga Taha Simsekyilmaz, Sakine Schumacher, David Möllmann, Julia Hackeng, Tilman M. Hundelshausen, Philipp von Weber, Christian Liehn, Elisa A. |
author_sort | Vajen, Tanja |
collection | PubMed |
description | Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression of atherosclerosis. A specifically designed compound (MKEY) to block this CCL5-CXCR4 interaction is investigated as a potential therapeutic in a model of myocardial ischemia/reperfusion (I/R) damage. 8 week-old male C57BL/6 mice were intravenously treated with MKEY or scrambled control (sMKEY) from 1 day before, until up to 7 days after I/R. By using echocardiography and intraventricular pressure measurements, MKEY treatment resulted in a significant decrease in infarction size and preserved heart function as compared to sMKEY-treated animals. Moreover, MKEY treatment significantly reduced the inflammatory reaction following I/R, as revealed by specific staining for neutrophils and monocyte/macrophages. Interestingly, MKEY treatment led to a significant reduction of citrullinated histone 3 in the infarcted tissue, showing that MKEY can prevent neutrophil extracellular trap formation in vivo. Disrupting chemokine heterodimers during myocardial I/R might have clinical benefits, preserving the therapeutic benefit of blocking specific chemokines, and in addition, reducing the inflammatory side effects maintaining normal immune defence. |
format | Online Article Text |
id | pubmed-6045661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60456612018-07-16 Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis Vajen, Tanja Koenen, Rory R. Werner, Isabella Staudt, Mareike Projahn, Delia Curaj, Adelina Sönmez, Tolga Taha Simsekyilmaz, Sakine Schumacher, David Möllmann, Julia Hackeng, Tilman M. Hundelshausen, Philipp von Weber, Christian Liehn, Elisa A. Sci Rep Article Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression of atherosclerosis. A specifically designed compound (MKEY) to block this CCL5-CXCR4 interaction is investigated as a potential therapeutic in a model of myocardial ischemia/reperfusion (I/R) damage. 8 week-old male C57BL/6 mice were intravenously treated with MKEY or scrambled control (sMKEY) from 1 day before, until up to 7 days after I/R. By using echocardiography and intraventricular pressure measurements, MKEY treatment resulted in a significant decrease in infarction size and preserved heart function as compared to sMKEY-treated animals. Moreover, MKEY treatment significantly reduced the inflammatory reaction following I/R, as revealed by specific staining for neutrophils and monocyte/macrophages. Interestingly, MKEY treatment led to a significant reduction of citrullinated histone 3 in the infarcted tissue, showing that MKEY can prevent neutrophil extracellular trap formation in vivo. Disrupting chemokine heterodimers during myocardial I/R might have clinical benefits, preserving the therapeutic benefit of blocking specific chemokines, and in addition, reducing the inflammatory side effects maintaining normal immune defence. Nature Publishing Group UK 2018-07-13 /pmc/articles/PMC6045661/ /pubmed/30006564 http://dx.doi.org/10.1038/s41598-018-29026-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Vajen, Tanja Koenen, Rory R. Werner, Isabella Staudt, Mareike Projahn, Delia Curaj, Adelina Sönmez, Tolga Taha Simsekyilmaz, Sakine Schumacher, David Möllmann, Julia Hackeng, Tilman M. Hundelshausen, Philipp von Weber, Christian Liehn, Elisa A. Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis |
title | Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis |
title_full | Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis |
title_fullStr | Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis |
title_full_unstemmed | Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis |
title_short | Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis |
title_sort | blocking ccl5-cxcl4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and netosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045661/ https://www.ncbi.nlm.nih.gov/pubmed/30006564 http://dx.doi.org/10.1038/s41598-018-29026-0 |
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