Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

Version 1 : Received: 18 June 2023 / Approved: 19 June 2023 / Online: 19 June 2023 (05:23:12 CEST)

A peer-reviewed article of this Preprint also exists.

Li, W.; Zhu, S.; Liu, J.; Liu, Z.; Zhou, H.; Zhang, Q.; Yang, Y.; Chen, L.; Guo, X.; Zhang, T.; Meng, L.; Chai, D.; Tang, G.; Li, X.; Yang, C. Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation. Molecules 2023, 28, 6035. Li, W.; Zhu, S.; Liu, J.; Liu, Z.; Zhou, H.; Zhang, Q.; Yang, Y.; Chen, L.; Guo, X.; Zhang, T.; Meng, L.; Chai, D.; Tang, G.; Li, X.; Yang, C. Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation. Molecules 2023, 28, 6035.

Abstract

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which has 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 study 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 cardiac fibrosis animal model. Here, results showed that 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 proinflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by 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.

Keywords

Heart failure; β-adrenergic receptor; cardiac fibrosis; cardiac inflammation; Bruton’s tyrosine kinase; Zanubrutinib

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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