Lycopene protects against myocardial ischemia-reperfusion injury by inhibiting FABP3-mediated pyroptosis in cardiac microvascular endothelial cells

Abstract

Cardiac microvascular damage exhibits a significant association with myocardial ischemia/reperfusion injury (MI/RI) development, which correlates with mitochondrial dysfunction. Lycopene has demonstrated pharmacological efficacy against cardiovascular diseases. Nevertheless, the potential roles and underlying mechanisms through which lycopene influences MI/RI remain incompletely understood. This study aimed to investigate the effect of lycopene on cardiac microvascular endothelial cells (CMECs) function in a rat model of MI/RI. This investigation sought to elucidate lycopene’s role in MI/RI and its mechanistic foundation. A rat MI/RI model was employed, and multiple experimental approaches were conducted, encompassing quantitative real-time polymerase chain reaction, western blot analysis, immunofluorescence microscopy, enzyme-linked immunosorbent assay, molecular docking, and molecular dynamics simulations. In vitro studies involved the establishment of a hypoxia-reoxygenation model using CMECs to evaluate lycopene’s contribution to pyroptosis suppression and mitochondrial dysfunction prevention. Lycopene was found to enhance mitochondrial function through inhibition of the YTHDF1/E2F8/FABP3 axis in CMECs, suppress cGAS-STING signaling pathway activation, reduce cellular inflammatory responses, and inhibit cellular pyroptosis. These effects ultimately resulted in improved CMECs function, enhanced microvascular integrity, and increased perfusion and oxygen delivery to cardiomyocytes.