Hypothermic machine perfusion alleviates DCD graft liver injury by inducing the expression of KLF2 and promoting macrophage efferocytosis

This study aims to investigate the protective effects and underlying mechanisms of hypothermic machine perfusion (HMP) on ischemia-reperfusion injury (IRI) in liver grafts from donation after cardiac death (DCD), with a specific focus on the regulation of KLF2 expression and its role in modulating macrophage efferocytosis. A DCD liver grafts model was established to evaluate the protective effects of HMP. KLF2 expression and macrophage efferocytosis were assessed in liver grafts. In vitro, human umbilical vein endothelial cells (HUVECs) were transfected to manipulate KLF2 expression and co-cultured with macrophages in a non-contact system to explore the endothelial–macrophage interaction. The efferocytosis agonist putrescine was administered in vivo to further assess its effect on DCD liver grafts. RNA sequencing (RNA-Seq) was conducted to analyze gene expression changes.