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Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III
Cardiac hypertrophy is an adaptive response to cardiac overload initially but turns into a decompensated condition chronically, leading to heart failure and sudden cardiac death. The molecular mechanisms involved in cardiac hypertrophy and the signaling pathways that contribute to the switch from co...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921739/ https://www.ncbi.nlm.nih.gov/pubmed/33664668 http://dx.doi.org/10.3389/fphar.2021.608523 |
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author | Zhong, Tiecheng Wang, Zonggui Niloy, Sayeman Islam Shen, Yue O’Rourke, Stephen T. Sun, Chengwen |
author_facet | Zhong, Tiecheng Wang, Zonggui Niloy, Sayeman Islam Shen, Yue O’Rourke, Stephen T. Sun, Chengwen |
author_sort | Zhong, Tiecheng |
collection | PubMed |
description | Cardiac hypertrophy is an adaptive response to cardiac overload initially but turns into a decompensated condition chronically, leading to heart failure and sudden cardiac death. The molecular mechanisms involved in cardiac hypertrophy and the signaling pathways that contribute to the switch from compensation to decompensation are not fully clear. The aim of the current study was to examine the role of PI3-kinases Class I (PI3KC1) and Class III (PI3KC3) in angiotensin (Ang) II-induced cardiac hypertrophy. The results demonstrate that treatment of cardiomyocytes with Ang II caused dose-dependent increases in autophagy, with an increasing phase followed by a decreasing phase. Ang II-induced autophagic increases were potentiated by inhibition of PI3KC1 with LY294002, but were impaired by inhibition of PI3KC3 with 3-methyladenine (3-MA). In addition, blockade of PI3KC1 significantly attenuated Ang II-induced ROS production and cardiomyocyte hypertrophy. In contrast, blockade of PI3KC3 potentiated Ang II-induced ROS production and cardiac hypertrophy. Moreover, blockade of PI3KC1 by overexpression of dominant negative p85 subunit of PI3KC1 significantly attenuated Ang II-induced cardiac hypertrophy in normotensive rats. Taken together, these results demonstrate that both PI3KC1 and PI3KC3 are involved in Ang II-induced cardiac hypertrophy by different mechanisms. Activation of PI3KC1 impairs autophagy activity, leading to accumulation of mitochondrial ROS, and, hence, cardiac hypertrophy. In contrast, activation of PI3KC3 improves autophagy activity, thereby reducing mitochondrial ROS and leads to a protective effect on Ang II-induced cardiac hypertrophy. |
format | Online Article Text |
id | pubmed-7921739 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79217392021-03-03 Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III Zhong, Tiecheng Wang, Zonggui Niloy, Sayeman Islam Shen, Yue O’Rourke, Stephen T. Sun, Chengwen Front Pharmacol Pharmacology Cardiac hypertrophy is an adaptive response to cardiac overload initially but turns into a decompensated condition chronically, leading to heart failure and sudden cardiac death. The molecular mechanisms involved in cardiac hypertrophy and the signaling pathways that contribute to the switch from compensation to decompensation are not fully clear. The aim of the current study was to examine the role of PI3-kinases Class I (PI3KC1) and Class III (PI3KC3) in angiotensin (Ang) II-induced cardiac hypertrophy. The results demonstrate that treatment of cardiomyocytes with Ang II caused dose-dependent increases in autophagy, with an increasing phase followed by a decreasing phase. Ang II-induced autophagic increases were potentiated by inhibition of PI3KC1 with LY294002, but were impaired by inhibition of PI3KC3 with 3-methyladenine (3-MA). In addition, blockade of PI3KC1 significantly attenuated Ang II-induced ROS production and cardiomyocyte hypertrophy. In contrast, blockade of PI3KC3 potentiated Ang II-induced ROS production and cardiac hypertrophy. Moreover, blockade of PI3KC1 by overexpression of dominant negative p85 subunit of PI3KC1 significantly attenuated Ang II-induced cardiac hypertrophy in normotensive rats. Taken together, these results demonstrate that both PI3KC1 and PI3KC3 are involved in Ang II-induced cardiac hypertrophy by different mechanisms. Activation of PI3KC1 impairs autophagy activity, leading to accumulation of mitochondrial ROS, and, hence, cardiac hypertrophy. In contrast, activation of PI3KC3 improves autophagy activity, thereby reducing mitochondrial ROS and leads to a protective effect on Ang II-induced cardiac hypertrophy. Frontiers Media S.A. 2021-02-16 /pmc/articles/PMC7921739/ /pubmed/33664668 http://dx.doi.org/10.3389/fphar.2021.608523 Text en Copyright © 2021 Zhong, Wang, Niloy, Shen, O’Rourke and Sun. 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) (http://creativecommons.org/licenses/by/4.0/) . 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 Zhong, Tiecheng Wang, Zonggui Niloy, Sayeman Islam Shen, Yue O’Rourke, Stephen T. Sun, Chengwen Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III |
title | Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III |
title_full | Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III |
title_fullStr | Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III |
title_full_unstemmed | Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III |
title_short | Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III |
title_sort | role of pi3-kinase in angiotensin ii-induced cardiac hypertrophy: class i versus class iii |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921739/ https://www.ncbi.nlm.nih.gov/pubmed/33664668 http://dx.doi.org/10.3389/fphar.2021.608523 |
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