The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3

2024/01/11 by Si Chen, Jian-Jun Gao, Jianjun Gao +18 · 14 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer, Lipids, and Metabolism #Ferroptosis and cancer prognosis #Cholesterol and Lipid Metabolism

paper · pdf · doi:10.1016/j.jlr.2024.100499

Abstract

, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

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