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Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling
We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adve...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339807/ https://www.ncbi.nlm.nih.gov/pubmed/28266659 http://dx.doi.org/10.1038/srep43958 |
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author | Pavo, Noemi Lukovic, Dominika Zlabinger, Katrin Zimba, Abelina Lorant, David Goliasch, Georg Winkler, Johannes Pils, Dietmar Auer, Katharina Jan Ankersmit, Hendrik Giricz, Zoltán Baranyai, Tamas Sárközy, Márta Jakab, András Garamvölgyi, Rita Emmert, Maximilian Y. Hoerstrup, Simon P. Hausenloy, Derek J. Ferdinandy, Péter Maurer, Gerald Gyöngyösi, Mariann |
author_facet | Pavo, Noemi Lukovic, Dominika Zlabinger, Katrin Zimba, Abelina Lorant, David Goliasch, Georg Winkler, Johannes Pils, Dietmar Auer, Katharina Jan Ankersmit, Hendrik Giricz, Zoltán Baranyai, Tamas Sárközy, Márta Jakab, András Garamvölgyi, Rita Emmert, Maximilian Y. Hoerstrup, Simon P. Hausenloy, Derek J. Ferdinandy, Péter Maurer, Gerald Gyöngyösi, Mariann |
author_sort | Pavo, Noemi |
collection | PubMed |
description | We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls. Hearts were explanted at 5 h (n = 6) and 24 h (n = 6), and transcriptomic profiling of the distal (ischemia-affected) and proximal (non-affected) anterior myocardial regions were analyzed by next generation sequencing (NGS) and post-processing with signaling pathway impact and pathway network analyses. In ischemic region, r-I/R induced early activation of Ca-, adipocytokine and insulin signaling pathways with key regulator STAT3, which was also upregulated in the remote areas together with clusterin (CLU) and TNF-alpha. During the late phase of cardioprotection, antigen immunomodulatory pathways were activated with upregulation of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intrinsic remote conditioning. The temporo-spatially differently activated pathways revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intrinsic remote conditioning for prevention of adverse remodeling. |
format | Online Article Text |
id | pubmed-5339807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53398072017-03-10 Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling Pavo, Noemi Lukovic, Dominika Zlabinger, Katrin Zimba, Abelina Lorant, David Goliasch, Georg Winkler, Johannes Pils, Dietmar Auer, Katharina Jan Ankersmit, Hendrik Giricz, Zoltán Baranyai, Tamas Sárközy, Márta Jakab, András Garamvölgyi, Rita Emmert, Maximilian Y. Hoerstrup, Simon P. Hausenloy, Derek J. Ferdinandy, Péter Maurer, Gerald Gyöngyösi, Mariann Sci Rep Article We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls. Hearts were explanted at 5 h (n = 6) and 24 h (n = 6), and transcriptomic profiling of the distal (ischemia-affected) and proximal (non-affected) anterior myocardial regions were analyzed by next generation sequencing (NGS) and post-processing with signaling pathway impact and pathway network analyses. In ischemic region, r-I/R induced early activation of Ca-, adipocytokine and insulin signaling pathways with key regulator STAT3, which was also upregulated in the remote areas together with clusterin (CLU) and TNF-alpha. During the late phase of cardioprotection, antigen immunomodulatory pathways were activated with upregulation of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intrinsic remote conditioning. The temporo-spatially differently activated pathways revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intrinsic remote conditioning for prevention of adverse remodeling. Nature Publishing Group 2017-03-07 /pmc/articles/PMC5339807/ /pubmed/28266659 http://dx.doi.org/10.1038/srep43958 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Pavo, Noemi Lukovic, Dominika Zlabinger, Katrin Zimba, Abelina Lorant, David Goliasch, Georg Winkler, Johannes Pils, Dietmar Auer, Katharina Jan Ankersmit, Hendrik Giricz, Zoltán Baranyai, Tamas Sárközy, Márta Jakab, András Garamvölgyi, Rita Emmert, Maximilian Y. Hoerstrup, Simon P. Hausenloy, Derek J. Ferdinandy, Péter Maurer, Gerald Gyöngyösi, Mariann Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
title | Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
title_full | Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
title_fullStr | Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
title_full_unstemmed | Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
title_short | Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
title_sort | sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339807/ https://www.ncbi.nlm.nih.gov/pubmed/28266659 http://dx.doi.org/10.1038/srep43958 |
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