Farrerol ameliorates diabetic cardiomyopathy by inhibiting ferroptosis

backgroundDiabetic cardiomyopathy (DCM) is the leading cause of cardiovascular disease-related mortality. Farrerol (FA) possesses anti-inflammatory and antioxidant properties. However, its role in regulating endothelial ferroptosis in DCM remains unknown.

aimTo investigate the beneficial effects of FA on cardiac microvascular dysfunction in DCM from the perspective of ferroptosis in endothelial cells (ECs).

methodsThe mice were fed a high-fat diet and injected with streptozotocin to induce DCM. DCM mice were orally administered FA (10 and 40 mg/kg/day) and a tail vein injection of the miR-29b-3p mimic or inhibitor for 24 weeks. Cardiac function and myocardial fibrosis were also analyzed. Cardiac microvascular function was assessed using immunofluorescence and transmission electron microscopy. Ferroptosis was analyzed using RNA sequencing, immunofluorescence, and western blotting.

resultsFA administration improved cardiac function, alleviated myocardial fibrosis, strengthened endothelial barrier function, suppressed endothelial inflammation, and preserved the microvascular structure in DCM mice. This improvement was associated with the inhibition of endothelial ferroptosis and downregulation of miR-29b-3p in ECs. Similar efficacy was observed after tail vein injection of the miR-29b-3p inhibitor. Inhibition of miR-29b-3p

conclusionTherefore, FA has a potential therapeutic effect on cardiac microvascular dysfunction by suppressing EC ferroptosis through the miR-29b-3p/SIRT1 axis.