Piezo1 activation protects against sepsis-induced myocardial dysfunction in a pilot study.

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 (Piezo1) 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. Piezo1mice exhibited more severe cardiac dysfunction and injury, especially with LPS treatment. DUSP3 protein levels were significantly elevated in Piezo1and LPS-treated hearts. Piezo1 exerted a protective role in SIMD, potentially through the modulation of DUSP3.