Work

HSP90B1 exacerbates myocardial infarction injury by promoting cardiomyocyte pyroptosis and is associated with M1-like macrophage polarization

Year: 2026

Type: article

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: 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: 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.

Source: Biology Direct

DOI: 10.1186/s13062-026-01026-5