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Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia
BACKGROUND: Exposure to intermittent hypoxia (IH) may enhance cardiac function and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the underlying mechanisms, we developed a cardioprotective IH model that was characterized at hemodynamic, biochemical and molecular levels. METHO...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790757/ https://www.ncbi.nlm.nih.gov/pubmed/24124584 http://dx.doi.org/10.1371/journal.pone.0076659 |
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author | Milano, Giuseppina Abruzzo, Provvidenza Maria Bolotta, Alessandra Marini, Marina Terraneo, Laura Ravara, Barbara Gorza, Luisa Vitadello, Maurizio Burattini, Sabrina Curzi, Davide Falcieri, Elisabetta von Segesser, Ludwig K. Samaja, Michele |
author_facet | Milano, Giuseppina Abruzzo, Provvidenza Maria Bolotta, Alessandra Marini, Marina Terraneo, Laura Ravara, Barbara Gorza, Luisa Vitadello, Maurizio Burattini, Sabrina Curzi, Davide Falcieri, Elisabetta von Segesser, Ludwig K. Samaja, Michele |
author_sort | Milano, Giuseppina |
collection | PubMed |
description | BACKGROUND: Exposure to intermittent hypoxia (IH) may enhance cardiac function and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the underlying mechanisms, we developed a cardioprotective IH model that was characterized at hemodynamic, biochemical and molecular levels. METHODS: Mice were exposed to 4 daily IH cycles (each composed of 2-min at 6-8% O(2) followed by 3-min reoxygenation for 5 times) for 14 days, with normoxic mice as controls. Mice were then anesthetized and subdivided in various subgroups for analysis of contractility (pressure-volume loop), morphology, biochemistry or resistance to I/R (30-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion and measurement of the area at risk and infarct size). In some mice, the phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin was administered (24 µg/kg ip) 15 min before LAD. RESULTS: We found that IH did not induce myocardial hypertrophy; rather both contractility and cardiac function improved with greater number of capillaries per unit volume and greater expression of VEGF-R2, but not of VEGF. Besides increasing the phosphorylation of protein kinase B (Akt) and the endothelial isoform of NO synthase with respect to control, IH reduced the infarct size and post-LAD proteins carbonylation, index of oxidative damage. Administration of wortmannin reduced the level of Akt phosphorylation and worsened the infarct size. CONCLUSION: We conclude that the PI3K/Akt pathway is crucial for IH-induced cardioprotection and may represent a viable target to reduce myocardial I/R injury. |
format | Online Article Text |
id | pubmed-3790757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37907572013-10-11 Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia Milano, Giuseppina Abruzzo, Provvidenza Maria Bolotta, Alessandra Marini, Marina Terraneo, Laura Ravara, Barbara Gorza, Luisa Vitadello, Maurizio Burattini, Sabrina Curzi, Davide Falcieri, Elisabetta von Segesser, Ludwig K. Samaja, Michele PLoS One Research Article BACKGROUND: Exposure to intermittent hypoxia (IH) may enhance cardiac function and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the underlying mechanisms, we developed a cardioprotective IH model that was characterized at hemodynamic, biochemical and molecular levels. METHODS: Mice were exposed to 4 daily IH cycles (each composed of 2-min at 6-8% O(2) followed by 3-min reoxygenation for 5 times) for 14 days, with normoxic mice as controls. Mice were then anesthetized and subdivided in various subgroups for analysis of contractility (pressure-volume loop), morphology, biochemistry or resistance to I/R (30-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion and measurement of the area at risk and infarct size). In some mice, the phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin was administered (24 µg/kg ip) 15 min before LAD. RESULTS: We found that IH did not induce myocardial hypertrophy; rather both contractility and cardiac function improved with greater number of capillaries per unit volume and greater expression of VEGF-R2, but not of VEGF. Besides increasing the phosphorylation of protein kinase B (Akt) and the endothelial isoform of NO synthase with respect to control, IH reduced the infarct size and post-LAD proteins carbonylation, index of oxidative damage. Administration of wortmannin reduced the level of Akt phosphorylation and worsened the infarct size. CONCLUSION: We conclude that the PI3K/Akt pathway is crucial for IH-induced cardioprotection and may represent a viable target to reduce myocardial I/R injury. Public Library of Science 2013-10-04 /pmc/articles/PMC3790757/ /pubmed/24124584 http://dx.doi.org/10.1371/journal.pone.0076659 Text en © 2013 Milano 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 Milano, Giuseppina Abruzzo, Provvidenza Maria Bolotta, Alessandra Marini, Marina Terraneo, Laura Ravara, Barbara Gorza, Luisa Vitadello, Maurizio Burattini, Sabrina Curzi, Davide Falcieri, Elisabetta von Segesser, Ludwig K. Samaja, Michele Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia |
title | Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia |
title_full | Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia |
title_fullStr | Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia |
title_full_unstemmed | Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia |
title_short | Impact of the Phosphatidylinositide 3-Kinase Signaling Pathway on the Cardioprotection Induced by Intermittent Hypoxia |
title_sort | impact of the phosphatidylinositide 3-kinase signaling pathway on the cardioprotection induced by intermittent hypoxia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790757/ https://www.ncbi.nlm.nih.gov/pubmed/24124584 http://dx.doi.org/10.1371/journal.pone.0076659 |
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