Oxidized Phospholipids Aggravate Hepatic Ischemia/Reperfusion Injury by Promoting Macrophage M1 Polarization Via Regulating the Wnt/β-catenin/Autophagy Axis.

Hepatic ischemia-reperfusion injury (IRI) remains an unavoidable consequence of partial hepatic resection and liver transplantation. Oxidative stress damages cellular lipid membranes, causing the formation of oxidized phospholipids (OxPLs), which are members of damage-associated molecular patterns (DAMPs). Nevertheless, the precise mechanism and significance of OxPLs in hepatic IRI are yet to be investigated. Our findings reveal that OxPLs accumulate excessively in the liver after IR. Compared to the control group, pre-treatment with E06 (an OxPLs-neutralizing antibody) significantly alleviates inflammatory cell infiltration and liver injury following IR. In vitro experiments show that OxPLs inhibit macrophage autophagy, thereby promoting M1 polarization. This regulatory effect depends on the activation of the Wnt/β-Catenin pathway by OxPLs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10753-025-02399-x.