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Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which have now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and i...

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Autores principales: Li, Wenqi, Zhu, Shuwen, Liu, Jing, Liu, Zhigang, Zhou, Honggang, Zhang, Qianyi, Yang, Yue, Chen, Li, Guo, Xiaowei, Zhang, Tiantian, Meng, Lingxin, Chai, Dan, Tang, Guodong, Li, Xiaohe, Yang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458081/
https://www.ncbi.nlm.nih.gov/pubmed/37630287
http://dx.doi.org/10.3390/molecules28166035
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author Li, Wenqi
Zhu, Shuwen
Liu, Jing
Liu, Zhigang
Zhou, Honggang
Zhang, Qianyi
Yang, Yue
Chen, Li
Guo, Xiaowei
Zhang, Tiantian
Meng, Lingxin
Chai, Dan
Tang, Guodong
Li, Xiaohe
Yang, Cheng
author_facet Li, Wenqi
Zhu, Shuwen
Liu, Jing
Liu, Zhigang
Zhou, Honggang
Zhang, Qianyi
Yang, Yue
Chen, Li
Guo, Xiaowei
Zhang, Tiantian
Meng, Lingxin
Chai, Dan
Tang, Guodong
Li, Xiaohe
Yang, Cheng
author_sort Li, Wenqi
collection PubMed
description (1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which have now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous research has demonstrated that Bruton’s tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation; (2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish a cardiac fibrosis animal model; (3) Results: In vivo: Results showed that the BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage pro-inflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by the BTK, STAT3, NF-κB, and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.
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spelling pubmed-104580812023-08-27 Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation Li, Wenqi Zhu, Shuwen Liu, Jing Liu, Zhigang Zhou, Honggang Zhang, Qianyi Yang, Yue Chen, Li Guo, Xiaowei Zhang, Tiantian Meng, Lingxin Chai, Dan Tang, Guodong Li, Xiaohe Yang, Cheng Molecules Article (1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which have now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous research has demonstrated that Bruton’s tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation; (2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish a cardiac fibrosis animal model; (3) Results: In vivo: Results showed that the BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage pro-inflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by the BTK, STAT3, NF-κB, and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation. MDPI 2023-08-12 /pmc/articles/PMC10458081/ /pubmed/37630287 http://dx.doi.org/10.3390/molecules28166035 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Wenqi
Zhu, Shuwen
Liu, Jing
Liu, Zhigang
Zhou, Honggang
Zhang, Qianyi
Yang, Yue
Chen, Li
Guo, Xiaowei
Zhang, Tiantian
Meng, Lingxin
Chai, Dan
Tang, Guodong
Li, Xiaohe
Yang, Cheng
Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation
title Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation
title_full Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation
title_fullStr Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation
title_full_unstemmed Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation
title_short Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation
title_sort zanubrutinib ameliorates cardiac fibrosis and inflammation induced by chronic sympathetic activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458081/
https://www.ncbi.nlm.nih.gov/pubmed/37630287
http://dx.doi.org/10.3390/molecules28166035
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