Key result
GI-Y2 improves diastolic function and reduces myocardial and mitochondrial damage in HFpEF mouse models.
Why the study?
The specific regulatory mechanisms by which gasdermin D mediates mitochondrial dysfunction and pyroptosis in HFpEF remain to be elucidated.
Does GI-Y2 improve mitochondrial damage and cardiomyocyte pyroptosis in HFpEF mouse models?
Does GI-Y2 improve mitochondrial damage and cardiomyocyte pyroptosis in HFpEF mouse models?
Gasdermin D inhibition with GI-Y2 attenuates mitochondrial damage and cardiomyocyte pyroptosis, improving cardiac function and exercise tolerance in a mouse model of HFpEF.
Heart failure with preserved ejection fraction (HFpEF) represents the most prevalent subtype of heart failure globally, with its underlying pathogenesis remaining incompletely elucidated. Pyroptosis and mitochondrial dysfunction have been implicated in HFpEF progression. In addition, gasdermin D (GSDMD) has been shown to mediate both mitochondrial dysfunction and pyroptosis, yet the specific regulatory mechanisms involved in HFpEF remain to be elucidated. In this study, we found that HFpEF mouse models exhibited elevated blood glucose and blood pressure, impaired diastolic cardiac function, upregulated serum NT-proBNP, increased heart weight-to-tibia length (HW/TL) ratio, reduced exercise tolerance, obvious myocardial structural damage, excessive mitochondrial ROS accumulation, increased mitochondrial GSDMD-N expression, mitochondrial morphological abnormalities, and activated myocardial pyroptosis pathway. Treatment with GI-Y2 significantly ameliorated these changes. Collectively, GSDMD contributes to HFpEF progression by promoting mitochondrial damage and cardiomyocyte pyroptosis.
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Chen et al. (2026) studied Heart failure with preserved ejection fraction (HFpEF). GI-Y2 vs. Untreated HFpEF mouse models was evaluated on HFpEF progression markers including mitochondrial damage and cardiomyocyte pyroptosis. Treatment with GI-Y2 significantly ameliorated impaired diastolic cardiac function, myocardial structural damage, and mitochondrial abnormalities in HFpEF mouse models.
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