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Updated: May 12, 2025
Author Spotlight: Advanced Integrated Model for Sepsis-Induced Myopathy and Single-Cell Metabolic Analysis
Published on: June 14, 2024
Piezo1 activation protects against sepsis-induced myocardial dysfunction in a pilot study
Angwei Gong1, Jing Dai2, Yan Zhao1
1Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei, 050000, China.
Abstract:
To explore the role and underlying mechanisms of Piezo1 in sepsis-induced myocardial dysfunction (SIMD). A SIMD model was established in mice via intraperitoneal lipopolysaccharide (LPS) injection. Cardiac function, histology, Piezo1 protein expression, and cardiac troponin T (cTnT) were assessed. Piezo1's role in SIMD was investigated using the agonist Yoda1, inhibitor GsMTx-4, and cardiomyocyte-specific Piezo1 knockout (Piezo1ΔCM) mice. Dual Specificity Phosphatase 3 (DUSP3) protein levels were also assessed to explore potential mechanisms. SIMD mice exhibited significantly impaired cardiac function, along with increased Piezo1 protein and cTnT levels. Piezo1 activation improved cardiac function and reduced tissue damage, while inhibition worsened SIMD. Piezo1ΔCM mice exhibited more severe cardiac dysfunction and injury, especially with LPS treatment. DUSP3 protein levels were significantly elevated in Piezo1ΔCM and LPS-treated hearts. Piezo1 exerted a protective role in SIMD, potentially through the modulation of DUSP3.
Insights
Piezo1 channels protect the heart during sepsis. Activating Piezo1 improved cardiac function in sepsis-induced myocardial dysfunction, while blocking it worsened the condition, suggesting a therapeutic target.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Sepsis-induced myocardial dysfunction (SIMD) is a critical complication of sepsis.
- The role of mechanosensitive ion channels, like Piezo1, in SIMD remains unclear.
Purpose of the Study:
- To investigate the function of Piezo1 in SIMD.
- To elucidate the underlying molecular mechanisms involving Dual Specificity Phosphatase 3 (DUSP3).
Main Methods:
- Established a SIMD mouse model using lipopolysaccharide (LPS).
- Utilized Piezo1 agonist (Yoda1), inhibitor (GsMTx-4), and cardiomyocyte-specific Piezo1 knockout (Piezo1ΔCM) mice.
- Assessed cardiac function, histology, Piezo1, cardiac troponin T (cTnT), and DUSP3 protein levels.
Main Results:
- SIMD mice showed impaired cardiac function, elevated Piezo1, and cTnT.
- Piezo1 activation improved cardiac function and reduced injury; inhibition exacerbated SIMD.
- Piezo1ΔCM mice exhibited worsened cardiac dysfunction and injury, with elevated DUSP3.
Conclusions:
- Piezo1 plays a protective role in sepsis-induced myocardial dysfunction.
- Piezo1 may exert its protective effects by modulating DUSP3 levels.
- Targeting Piezo1 could be a potential therapeutic strategy for SIMD.
