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Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction
The level of maladaptive myocardial remodeling consistently contributes to the poor prognosis of patients following a myocardial infarction (MI). In this study, we investigated whether and how sodium tanshinone IIA sulfonate (STS) would attenuate the post-infarct cardiac remodeling in mice model of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639725/ https://www.ncbi.nlm.nih.gov/pubmed/31354493 http://dx.doi.org/10.3389/fphar.2019.00779 |
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author | Mao, Shuai Vincent, Matthew Chen, Maosheng Zhang, Minzhou Hinek, Aleksander |
author_facet | Mao, Shuai Vincent, Matthew Chen, Maosheng Zhang, Minzhou Hinek, Aleksander |
author_sort | Mao, Shuai |
collection | PubMed |
description | The level of maladaptive myocardial remodeling consistently contributes to the poor prognosis of patients following a myocardial infarction (MI). In this study, we investigated whether and how sodium tanshinone IIA sulfonate (STS) would attenuate the post-infarct cardiac remodeling in mice model of MI developing after surgical ligation of the left coronary artery. All mice subjected to experimental MI or to the sham procedure were then treated for the following 4 weeks, either with STS or with a vehicle alone. Results of our studies indicated that STS treatment of MI mice prevented the left ventricular dilatation and improved their cardiac function. Results of further tests, aimed at mechanistic explanation of the beneficial effects of STS, indicated that treatment with this compound enhanced the autophagy and, at the same time, inhibited apoptosis of the cardiomyocytes. Meaningfully, we have also established that myocardium of STS-treated mice displayed significantly higher levels of adenosine monophosphate kinase than their untreated counterparts and that this effect additionally associated with the significantly diminished activities of apoptotic promoters: mammalian target of rapamycin and P70S6 kinase. Moreover, we also found that additional administration of the adenosine monophosphate kinase inhibitor (compound C) or autophagy inhibitor (chloroquine) practically eliminated the observed beneficial effects of STS. In conclusion, we suggest that the described multistage mechanism triggered by STS treatment enhanced autophagy, thereby attenuating pathologic remodeling of the post-infarct hearts. |
format | Online Article Text |
id | pubmed-6639725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66397252019-07-26 Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction Mao, Shuai Vincent, Matthew Chen, Maosheng Zhang, Minzhou Hinek, Aleksander Front Pharmacol Pharmacology The level of maladaptive myocardial remodeling consistently contributes to the poor prognosis of patients following a myocardial infarction (MI). In this study, we investigated whether and how sodium tanshinone IIA sulfonate (STS) would attenuate the post-infarct cardiac remodeling in mice model of MI developing after surgical ligation of the left coronary artery. All mice subjected to experimental MI or to the sham procedure were then treated for the following 4 weeks, either with STS or with a vehicle alone. Results of our studies indicated that STS treatment of MI mice prevented the left ventricular dilatation and improved their cardiac function. Results of further tests, aimed at mechanistic explanation of the beneficial effects of STS, indicated that treatment with this compound enhanced the autophagy and, at the same time, inhibited apoptosis of the cardiomyocytes. Meaningfully, we have also established that myocardium of STS-treated mice displayed significantly higher levels of adenosine monophosphate kinase than their untreated counterparts and that this effect additionally associated with the significantly diminished activities of apoptotic promoters: mammalian target of rapamycin and P70S6 kinase. Moreover, we also found that additional administration of the adenosine monophosphate kinase inhibitor (compound C) or autophagy inhibitor (chloroquine) practically eliminated the observed beneficial effects of STS. In conclusion, we suggest that the described multistage mechanism triggered by STS treatment enhanced autophagy, thereby attenuating pathologic remodeling of the post-infarct hearts. Frontiers Media S.A. 2019-07-12 /pmc/articles/PMC6639725/ /pubmed/31354493 http://dx.doi.org/10.3389/fphar.2019.00779 Text en Copyright © 2019 Mao, Vincent, Chen, Zhang and Hinek http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Mao, Shuai Vincent, Matthew Chen, Maosheng Zhang, Minzhou Hinek, Aleksander Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction |
title | Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction |
title_full | Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction |
title_fullStr | Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction |
title_full_unstemmed | Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction |
title_short | Exploration of Multiple Signaling Pathways Through Which Sodium Tanshinone IIA Sulfonate Attenuates Pathologic Remodeling Experimental Infarction |
title_sort | exploration of multiple signaling pathways through which sodium tanshinone iia sulfonate attenuates pathologic remodeling experimental infarction |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639725/ https://www.ncbi.nlm.nih.gov/pubmed/31354493 http://dx.doi.org/10.3389/fphar.2019.00779 |
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