HSP90B1 drives cardiomyocyte pyroptosis and inflammation after heart attack, mouse study finds

In a study published in Biology Direct, researchers report that HSP90B1, an endoplasmic reticulum chaperone, is elevated in heart tissue after myocardial infarction in both humans and mice, and that reducing its levels in mice improved survival and cardiac function following infarction. The work positions HSP90B1 as a regulator of pyroptosis, an inflammatory form of programmed cell death, in injured cardiomyocytes.

In all three settings, HSP90B1 levels rose. These partial-knockout animals showed better post-MI survival, preserved cardiac function, and reduced adverse remodeling of the heart muscle compared with normal mice, suggesting that full HSP90B1 expression contributes to the damage cascade.

In the cell experiments, HSP90B1 promoted OGD-induced pyroptosis in AC16 cardiomyocytes and was associated with activation of NF-κB and NLRP3 signaling, two pathways central to inflammatory cell death. When the researchers pharmacologically inhibited these pathways, pyroptosis-related responses diminished.

Using a non-contact Transwell co-culture system, in which cardiomyocytes and macrophages share medium but cannot touch, the researchers found that the level of HSP90B1 expression in cardiomyocytes influenced the pro-inflammatory phenotype of macrophages. Specifically, cardiomyocyte HSP90B1 was associated with M1-like macrophage polarization, a pro-inflammatory activation state that contributes to adverse cardiac remodeling after MI.

The authors conclude that HSP90B1 acts as a key regulator of cardiomyocyte pyroptotic signaling and post-MI inflammatory remodeling. Because the findings rest largely on animal models, a human cell line under artificial oxygen-glucose deprivation, and heterozygous rather than complete gene deletion, they are best understood as mechanistic associations rather than proof of a therapeutic target. The article was published as open access on 22 October 2026 under Biology Direct’s early-release model, meaning the peer-reviewed, accepted version is citable but may still undergo further edits before the final Version of Record replaces it.

Subject of Research: The role of the endoplasmic reticulum chaperone HSP90B1 in cardiomyocyte pyroptosis and post-infarction inflammatory remodeling after myocardial infarction.

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

Article References: Wang, Y., Ge, J., Zhang, Y., Shi, K., Bao, J., Dai, M., Zhang, X., Liu, X., Lin, J., Tang, Z., Sun, L., & Yu, X. (2026). HSP90B1 exacerbates myocardial infarction injury by promoting cardiomyocyte pyroptosis and is associated with M1-like macrophage polarization. Biology Direct. https://doi.org/10.1186/s13062-026-01026-5

Image Credits: AI Generated

DOI: 10.1186/s13062-026-01026-5

Keywords: HSP90B1, myocardial infarction, pyroptosis, NLRP3, NF-κB, macrophage polarization, cardiac remodeling, oxygen-glucose deprivation, inflammation, cardiomyocytes, exacerbates, myocardial