HSP90B1 exacerbates myocardial infarction injury by promoting cardiomyocyte pyroptosis and is associated with M1-like macrophage polarization
- 1Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, 9th, Lvshun South Road, Dalian, Liaoning Province 116044 China
- 2Key Laboratory of Intervention in Tumor Metastasis, Dalian, Liaoning Province China
- 3Key Laboratory of Cancer Stem Cell Research, Dalian, Liaoning Province China
Abstract
Background: Excessive inflammation contributes to adverse cardiac remodeling after myocardial infarction (MI), but the mechanisms linking cardiomyocyte injury to immune activation remain incompletely understood. Here, we investigated the role of the endoplasmic reticulum chaperone HSP90B1 in cardiomyocyte injury and inflammatory crosstalk after MI.
Methods: We examined HSP90B1 expression in human myocardial tissues, mouse MI hearts, and oxygen-glucose deprivation (OGD)-treated AC16 cardiomyocytes. Hsp90b1+/− mice were used to evaluate post-MI survival, cardiac function, and myocardial remodeling. HSP90B1 was selectively silenced or overexpressed in AC16 cardiomyocytes, and transcriptomic and pharmacological analyses were performed to investigate the signaling pathways involved. A non-contact Transwell co-culture system was also established to assess the effects of cardiomyocyte HSP90B1 on macrophage inflammatory activation.
Results: HSP90B1 was increased in human and mouse myocardial tissues after MI and in OGD-treated AC16 cardiomyocytes. Hsp90b1+/− mice showed improved post-MI survival, preserved cardiac function, and reduced adverse remodeling. In AC16 cardiomyocytes, HSP90B1 promoted OGD-induced pyroptosis and was associated with activation of NF-κB/NLRP3 signaling, whereas pharmacological inhibition of these pathways reduced pyroptosis-related responses. In a non-contact cardiomyocyte–macrophage co-culture system, cardiomyocyte HSP90B1 expression influenced the pro-inflammatory phenotype of macrophages.
Conclusions: Our findings identify HSP90B1 as a key regulator of cardiomyocyte pyroptotic signaling and post-MI inflammatory remodeling, with cardiomyocyte HSP90B1 expression associated with M1-like macrophage polarization.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13062-026-01026-5.
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BibTeX
@article{wang2026hsp90b1,
title = {{HSP90B1 exacerbates myocardial infarction injury by promoting cardiomyocyte pyroptosis and is associated with M1-like macrophage polarization}},
author = {Yemin Wang and Jiaqian Ge and Ying Zhang and Keke Shi and Jianrong Bao and Mingxiu Dai and Xiaopeng Zhang and Xuexue Liu and Jiaqian Lin and Zilong Tang and Lei Sun and Xiao Yu},
journal = {Biology Direct},
year = {2026},
month = oct,
doi = {10.1186/s13062-026-01026-5},
url = {https://doi.org/10.1186/s13062-026-01026-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - HSP90B1 exacerbates myocardial infarction injury by promoting cardiomyocyte pyroptosis and is associated with M1-like macrophage polarization
AU - Yemin Wang
AU - Jiaqian Ge
AU - Ying Zhang
AU - Keke Shi
AU - Jianrong Bao
AU - Mingxiu Dai
AU - Xiaopeng Zhang
AU - Xuexue Liu
AU - Jiaqian Lin
AU - Zilong Tang
AU - Lei Sun
AU - Xiao Yu
PY - 2026
DA - 2026/10/22
JO - Biology Direct
DO - 10.1186/s13062-026-01026-5
UR - https://doi.org/10.1186/s13062-026-01026-5
AB - Background: Excessive inflammation contributes to adverse cardiac remodeling after myocardial infarction (MI), but the mechanisms linking cardiomyocyte injury to immune activation remain incompletely understood. Here, we investigated the role of the endoplasmic reticulum chaperone HSP90B1 in cardiomyocyte injury and inflammatory crosstalk after MI. Methods: We examined HSP90B1 expression in human myocardial tissues, mouse MI hearts, and oxygen-glucose deprivation (OGD)-treated AC16 cardiomyocytes. Hsp90b1+/− mice were used to evaluate post-MI survival, cardiac function, and myocardial remodeling. HSP90B1 was selectively silenced or overexpressed in AC16 cardiomyocytes, and transcriptomic and pharmacological analyses were performed to investigate the signaling pathways involved. A non-contact Transwell co-culture system was also established to assess the effects of cardiomyocyte HSP90B1 on macrophage inflammatory activation. Results: HSP90B1 was increased in human and mouse myocardial tissues after MI and in OGD-treated AC16 cardiomyocytes. Hsp90b1+/− mice showed improved post-MI survival, preserved cardiac function, and reduced adverse remodeling. In AC16 cardiomyocytes, HSP90B1 promoted OGD-induced pyroptosis and was associated with activation of NF-κB/NLRP3 signaling, whereas pharmacological inhibition of these pathways reduced pyroptosis-related responses. In a non-contact cardiomyocyte–macrophage co-culture system, cardiomyocyte HSP90B1 expression influenced the pro-inflammatory phenotype of macrophages. Conclusions: Our findings identify HSP90B1 as a key regulator of cardiomyocyte pyroptotic signaling and post-MI inflammatory remodeling, with cardiomyocyte HSP90B1 expression associated with M1-like macrophage polarization. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13062-026-01026-5.
SN - 1745-6150
ER -