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Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension

AIM: Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and repe...

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Autores principales: Ohm, Ingrid Kristine, Gao, Erhe, Belland Olsen, Maria, Alfsnes, Katrine, Bliksøen, Marte, Øgaard, Jonas, Ranheim, Trine, Nymo, Ståle Haugset, Holmen, Yangchen Dhondup, Aukrust, Pål, Yndestad, Arne, Vinge, Leif Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134200/
https://www.ncbi.nlm.nih.gov/pubmed/25126943
http://dx.doi.org/10.1371/journal.pone.0104407
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author Ohm, Ingrid Kristine
Gao, Erhe
Belland Olsen, Maria
Alfsnes, Katrine
Bliksøen, Marte
Øgaard, Jonas
Ranheim, Trine
Nymo, Ståle Haugset
Holmen, Yangchen Dhondup
Aukrust, Pål
Yndestad, Arne
Vinge, Leif Erik
author_facet Ohm, Ingrid Kristine
Gao, Erhe
Belland Olsen, Maria
Alfsnes, Katrine
Bliksøen, Marte
Øgaard, Jonas
Ranheim, Trine
Nymo, Ståle Haugset
Holmen, Yangchen Dhondup
Aukrust, Pål
Yndestad, Arne
Vinge, Leif Erik
author_sort Ohm, Ingrid Kristine
collection PubMed
description AIM: Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R) reduces infarct size, but the consequence of TLR9 activation timed to the onset of ischemia is not known. METHODS AND RESULTS: The TLR9-agonist; CpG B was injected i.p. in C57BL/6 mice immediately after induction of ischemia (30 minutes). Final infarct size, as well as area-at-risk, was measured after 24 hours of reperfusion. CpG B injection resulted in a significant increase in circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically, clear evidence of reduced cardiac infiltration of both monocytes and granulocytes could be demonstrated in I/R mice treated with CpG B (immunocytochemistry, myeloperoxidase activity and mRNA expression patterns). In addition, systemic TLR9 activation elicited significant alterations of cardiac inflammatory genes. Despite these biochemical and cellular changes, there was no difference in infarct size between vehicle and CpG B treated I/R mice. CONCLUSION: Systemic TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter final infarct size despite causing clear alterations of both systemic and cardiac inflammatory parameters. Our results question the clinical usefulness of TLR9 activation during cardiac I/R.
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spelling pubmed-41342002014-08-19 Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension Ohm, Ingrid Kristine Gao, Erhe Belland Olsen, Maria Alfsnes, Katrine Bliksøen, Marte Øgaard, Jonas Ranheim, Trine Nymo, Ståle Haugset Holmen, Yangchen Dhondup Aukrust, Pål Yndestad, Arne Vinge, Leif Erik PLoS One Research Article AIM: Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R) reduces infarct size, but the consequence of TLR9 activation timed to the onset of ischemia is not known. METHODS AND RESULTS: The TLR9-agonist; CpG B was injected i.p. in C57BL/6 mice immediately after induction of ischemia (30 minutes). Final infarct size, as well as area-at-risk, was measured after 24 hours of reperfusion. CpG B injection resulted in a significant increase in circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically, clear evidence of reduced cardiac infiltration of both monocytes and granulocytes could be demonstrated in I/R mice treated with CpG B (immunocytochemistry, myeloperoxidase activity and mRNA expression patterns). In addition, systemic TLR9 activation elicited significant alterations of cardiac inflammatory genes. Despite these biochemical and cellular changes, there was no difference in infarct size between vehicle and CpG B treated I/R mice. CONCLUSION: Systemic TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter final infarct size despite causing clear alterations of both systemic and cardiac inflammatory parameters. Our results question the clinical usefulness of TLR9 activation during cardiac I/R. Public Library of Science 2014-08-15 /pmc/articles/PMC4134200/ /pubmed/25126943 http://dx.doi.org/10.1371/journal.pone.0104407 Text en © 2014 Ohm et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ohm, Ingrid Kristine
Gao, Erhe
Belland Olsen, Maria
Alfsnes, Katrine
Bliksøen, Marte
Øgaard, Jonas
Ranheim, Trine
Nymo, Ståle Haugset
Holmen, Yangchen Dhondup
Aukrust, Pål
Yndestad, Arne
Vinge, Leif Erik
Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension
title Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension
title_full Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension
title_fullStr Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension
title_full_unstemmed Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension
title_short Toll-Like Receptor 9-Activation during Onset of Myocardial Ischemia Does Not Influence Infarct Extension
title_sort toll-like receptor 9-activation during onset of myocardial ischemia does not influence infarct extension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134200/
https://www.ncbi.nlm.nih.gov/pubmed/25126943
http://dx.doi.org/10.1371/journal.pone.0104407
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