The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure

• DOI: 10.1186/s12967-024-05192-w
• Publication Date: 2024-04-21T02:50:22Z
• Authors: Anna De Bartolo; Teresa Pasqua; Naomi Romeo; Vittoria Rago; Ida Perrotta; Francesca Giordano; Maria Concetta Gr...; Alessandro Marrone; Rosa Mazza; Maria Carmela Cerra; Benjamin Lefranc; Jérôme Leprince; Youssef Anouar; Tommaso Angelone; Carmine Rocca
• Keywords: Pathophysiology

Abstract Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute protection. However, its action in chronic settings dysfunction is not understood. Here, we investigated role SELENOT pathophysiology HF: (i) by designing small peptide (PSELT), recapitulating activity via redox site, assessed beneficial preclinical model HF [aged spontaneously hypertensive (SHHF) rats] against isoproterenol (ISO)-induced ventricular H9c2 adult human AC16 cardiomyocytes; (ii) evaluating intra-cardiomyocyte production secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, severe ultrastructural alterations, while counteracting mediators fibrosis, aging, DNA damage restoring desmin downregulation upregulation failing hearts. In hemodynamic assessment, improved contractile impairment at baseline following ischemia/reperfusion reduced infarct size normal At cellular level, counteracted ISO-mediated alterations through motif, mitigating ISO-triggered intracellular secretion, phenomenon presumably reflects extent cell damage. Altogether, these results indicate could represent novel sensor cardiomyocytes potential PSELT-based new therapeutic approach HF. Graphical