2. Academic Validation
  3. Yoda1/Piezo1 Alleviates Lipopolysaccharide-Induced Cardiac Injury via AMPK-Mediated Mitophagy

Yoda1/Piezo1 Alleviates Lipopolysaccharide-Induced Cardiac Injury via AMPK-Mediated Mitophagy

  • Cardiovasc Toxicol. 2025 Jul 24. doi: 10.1007/s12012-025-10045-z.
Yiheng Yang 1 2,  Qingshan Tian 1,  Feng Qiu 3 4,  Jiangfeng Tang 1,  Zhenzhong Zheng 5 6,  Peng Yang 7
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 2 Department of Cardiology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330000, Jiangxi, China.
  • 3 Department of Oncology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330000, Jiangxi, China.
  • 4 Nanchang Key Laboratory of Tumor Gene Diagnosis and Innovative Treatment Research, Nanchang, 330000, Jiangxi, China.
  • 5 Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China. greateful@163.com.
  • 6 Department of Cardiology, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China. greateful@163.com.
  • 7 Department of Cardiology, Jiangxi Provincial People's Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, 330006, Jiangxi, China. yangpeng202203@163.com.
PMID: 40705239 DOI: 10.1007/s12012-025-10045-z
Abstract

The role of the mechanosensitive ion channel Piezo1 in septic cardiomyopathy remains unclear. This study investigated the role of Piezo1 in septic cardiomyopathy, focusing on the effects of its activation by Yoda1, an effective selective Piezo1 agonist, in LPS-induced cardiac injury models. In vivo, Yoda1 treatment improved cardiac function, enhanced Mitophagy, and activated AMPK signaling in LPS-treated mice. In vitro, Yoda1 protected primary cultured cardiomyocytes from LPS-induced oxidative stress, improved mitochondrial function, and increased PINK1/Parkin-mediated Mitophagy, whereas the Piezo1 inhibitor GsMTx4 had minimal effects. Western blot analysis confirmed the activation of the PINK1/Parkin and AMPK pathways by Yoda1 in cardiomyocytes. Notably, inhibiting AMPK signaling reduced the protective effects of Yoda1, underscoring the crucial role of AMPK in Mitophagy regulation. These findings indicate that Yoda1 may serve as a potential therapeutic agent for LPS-induced cardiac injury, acting primarily through the regulation of Mitophagy via the Piezo1/AMPK/PINK1/Parkin signaling pathway.

Keywords

AMPK; Peizo1; Septic cardiomyopathy; Yoda1.

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