Lutein suppresses ferroptosis of cardiac microvascular endothelial cells via positive regulation of IRF in cardiac hypertrophy

Abstract

Cardiac microvascular dysfunction contributes to cardiac hypertrophy (CH) and can progress to heart failure. Lutein is a carotenoid with various pharmacological properties, such as anti-apoptotic, anti-inflammatory, and antioxidant effects. Limited research has been conducted on the effects of lutein on pressure overload-induced CH. Studies have shown that CH is accompanied by ferroptosis in the cardiac microvascular endothelial cells (CMECs). This study aimed to investigate the effect of lutein on ferroptosis of CMECs in CH. The transcription factor interferon regulatory factor (IRF) is associated with immune system function, tumor suppression, and apoptosis. The results of this study suggested that pressure overload primarily inhibits IRF expression, resulting in endothelial ferroptosis. Administration of lutein increased the expression of IRF, providing protection to endothelial cells during pressure overload. IRF silencing downregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, leading to the induction of ferroptosis in CMECs. Lutein supplementation suppressed endothelial ferroptosis by upregulating IRF. These data suggest that IRF may function as a transcription factor for SLC7A11 and that lutein represses ferroptosis in CMECs by upregulating IRF expression. Therefore, targeting IRF may be a promising therapeutic strategy for effective cardioprotection in patients with CH and heart failure.

Keywords: Cardiac hypertrophy; Cardiac microvascular endothelial cells; Ferroptosis; Lutein; Transcription factor.