What question did this study set out to answer?

To investigate the role of macrophage Piezo1 in mediating polarization during myocardial ischemia-reperfusion injury.

February 8, 2026

Mechanical channel protein Piezo1 mediates macrophage polarization to exacerbate myocardial ischemia-reperfusion injury

Key Points

To investigate the role of macrophage Piezo1 in mediating polarization during myocardial ischemia-reperfusion injury.
Established a myocardial ischemia-reperfusion injury model in mice.
Utilized Yoda1 to activate Piezo1 and adeno-associated virus for macrophage Piezo1 knockdown.
Performed in vitro studies with Yoda1 and siRNA to explore Piezo1's effects on macrophage polarization.
Increased Piezo1 expression in myocardial macrophages post-MI/RI.
Piezo1 activation worsened MI/RI severity, while knockdown alleviated it.
Significant reduction of inflammatory and M1 macrophage markers in Piezo1 knockdown mice.
Activation of Piezo1 led to Ca2+ influx causing mitochondrial dysfunction and increased inflammatory cytokines.

Abstract

Abstract Objective Macrophage polarization plays an important role in myocardial ischemia-reperfusion injury (MI/RI), but the mechanism driving macrophage polarization is not clear. As an important mechanical-gated channel protein, Piezo1 can mediate Ca2+ influx to affect the function of macrophages. However, the role and mechanism of macrophage Piezo1 in MI/RI remain elusive. Methods MI/RI model was established by ligation of the left anterior descending coronary artery in C57BL/6 mice. Piezo1 activation and macrophage Piezo1 knockdown mouse models were constructed by in vivo injection of Yoda1 (a Piezo1 specific agonist) and adeno-associated virus (F4/80-shPiezo1), respectively. In vitro , Yoda1 and siRNA were used to investigate the effect and mechanism of Piezo1 on macrophage polarization. Results The expression of Piezo1 in myocardial macrophages was increased after MI/RI. Activation of Piezo1 aggravated MI/RI, while macrophage-specific knockdown of Piezo1 alleviated the severity of MI/RI. Compared with the control group, inflammatory markers (TNFα, IL-1α, and IL-6) and M1-type macrophage markers (CD80, CD86, and NOS2) were significantly decreased in the myocardium of macrophage specific Piezo1 knockdown mice. In addition, the effect of Piezo1 activation on M1 polarization of macrophages was further determined in vitro. Mechanically, we found that the specific activation of Piezo1 induced a large amount of Ca2+ influx, resulting in the reduction of mitochondrial calmodulin (MCU) expression, the increase of mitochondrial oxidative stress level, and mitochondrial metabolic dysfunction, leading to the activation of downstream transcription factors Spi-1 and NF-κB, and finally promoting the M1 polarization of macrophages and the increase of proinflammatory cytokines. Conclusion Our results suggest that macrophage Piezo1 plays a key role in the inflammatory response of MI/RI, and the Piezo1-MCU-SPI1 /NF-κB signaling axis may be a potential therapeutic target for MI/RI.

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Cite This Study

Liu et al. (Sat,) studied this question.

synapsesocial.com/papers/698828100fc35cd7a88473eb https://doi.org/https://doi.org/10.1093/eurheartj/ehaf784.1907

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