Mitigation of ischemia/reperfusion injury via selenium nanoparticles: Suppression of STAT1 to inhibit cardiomyocyte oxidative stress and inflammation.

Abstract

Ischemia/reperfusion injury (I/RI) following myocardial infarction, a leading cause of global morbidity and mortality, is characterized by detrimental oxidative stress and inflammation. In response, we proposed an I/RI alleviation strategy using the intravenous injection of spherical selenium nanoparticles (SeNPs) synthesized by a template method. Single-cell sequencing revealed these proposed SeNPs exhibited exceptional antioxidant and anti-inflammatory properties, disrupting the STAT1-ROS cycle, therefore preserving mitochondrial respiration and inhibiting caspase-mediated cardiomyocyte apoptosis. Additionally, SeNPs reduced macrophage infiltration and diminished the subsequent release of inflammatory mediators during I/RI. In vivo, SeNPs significantly improved myocardial function while decreasing myocardial apoptosis and fibrosis. These results collectively demonstrated that template method synthesized spherical SeNPs may serve as a promising candidate for enhancing myocardial infarction treatments, while the suppression of STAT1 could be a pivotal mechanism for alleviating ischemia/reperfusion injury following myocardial infarction.