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Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18
Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether infl...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024560/ https://www.ncbi.nlm.nih.gov/pubmed/33842546 http://dx.doi.org/10.3389/fmolb.2021.641585 |
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author | Dai, Fangjie Li, Xuan Li, Xia Ding, Zhiwen Xu, Ran Yin, Peipei Wang, Shijun Ge, Junbo Wu, Jian Zou, Yunzeng |
author_facet | Dai, Fangjie Li, Xuan Li, Xia Ding, Zhiwen Xu, Ran Yin, Peipei Wang, Shijun Ge, Junbo Wu, Jian Zou, Yunzeng |
author_sort | Dai, Fangjie |
collection | PubMed |
description | Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether inflammation plays a role in the antecedent protective effects of HP remains unknown. Caspase-1 is a critical proinflammatory caspase that also induces pyroptosis; thus, we investigated the role of caspase-1 using a unique model of HP in mice subjected longitudinally to 3 days of transverse aortic constriction (TAC 3d), 4 days of de-constriction (De-TAC 4d), and 4 weeks of Re-TAC (Re-TAC 4W). Echocardiography, hemodynamics, histology, PCR, and western blot confirmed preserved cardiac function, alleviated myocardial hypertrophy and fibrosis, and less activated hypertrophic signaling effectors in Re-TAC 4W mice, compared with TAC 4W mice. Mechanistically, caspase-1 and its downstream targets IL-1β and IL-18, but not GSDMD, were less activated in Re-TAC 4W mice. Furthermore, in HP mice with AAV-9-mediated cardiac-specific caspase-1 overexpression, the salutary effects of HP were remarkably abrogated, as evidenced by exacerbated cardiac remodeling, dysfunction, and activation of IL-1β and IL-18. Collectively, this study revealed a previously unrecognized involvement of caspase-1 in cardiac HP by regulation of IL-1β and IL-18 and shed light on caspase-1 as an antecedent indicator and target for cardiac hypertrophy. |
format | Online Article Text |
id | pubmed-8024560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80245602021-04-08 Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 Dai, Fangjie Li, Xuan Li, Xia Ding, Zhiwen Xu, Ran Yin, Peipei Wang, Shijun Ge, Junbo Wu, Jian Zou, Yunzeng Front Mol Biosci Molecular Biosciences Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether inflammation plays a role in the antecedent protective effects of HP remains unknown. Caspase-1 is a critical proinflammatory caspase that also induces pyroptosis; thus, we investigated the role of caspase-1 using a unique model of HP in mice subjected longitudinally to 3 days of transverse aortic constriction (TAC 3d), 4 days of de-constriction (De-TAC 4d), and 4 weeks of Re-TAC (Re-TAC 4W). Echocardiography, hemodynamics, histology, PCR, and western blot confirmed preserved cardiac function, alleviated myocardial hypertrophy and fibrosis, and less activated hypertrophic signaling effectors in Re-TAC 4W mice, compared with TAC 4W mice. Mechanistically, caspase-1 and its downstream targets IL-1β and IL-18, but not GSDMD, were less activated in Re-TAC 4W mice. Furthermore, in HP mice with AAV-9-mediated cardiac-specific caspase-1 overexpression, the salutary effects of HP were remarkably abrogated, as evidenced by exacerbated cardiac remodeling, dysfunction, and activation of IL-1β and IL-18. Collectively, this study revealed a previously unrecognized involvement of caspase-1 in cardiac HP by regulation of IL-1β and IL-18 and shed light on caspase-1 as an antecedent indicator and target for cardiac hypertrophy. Frontiers Media S.A. 2021-03-24 /pmc/articles/PMC8024560/ /pubmed/33842546 http://dx.doi.org/10.3389/fmolb.2021.641585 Text en Copyright © 2021 Dai, Li, Li, Ding, Xu, Yin, Wang, Ge, Wu and Zou. 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 | Molecular Biosciences Dai, Fangjie Li, Xuan Li, Xia Ding, Zhiwen Xu, Ran Yin, Peipei Wang, Shijun Ge, Junbo Wu, Jian Zou, Yunzeng Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 |
title | Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 |
title_full | Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 |
title_fullStr | Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 |
title_full_unstemmed | Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 |
title_short | Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18 |
title_sort | caspase-1 abrogates the salutary effects of hypertrophic preconditioning in pressure overload hearts via il-1β and il-18 |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024560/ https://www.ncbi.nlm.nih.gov/pubmed/33842546 http://dx.doi.org/10.3389/fmolb.2021.641585 |
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