TREM2 macrophage promotes cardiac repair in myocardial infarction by reprogramming metabolism via SLC25A53.

ABSTRACT: Efferocytosis and metabolic reprogramming of macrophages play crucial roles in myocardial infarction (MI) repair. TREM2 has been proven to participate in phagocytosis and metabolism, but how it modulates myocardial infarction remains unclear. In this study, we showed that macrophage-specific TREM2 deficiency worsened cardiac function and impaired post-MI repair. Using RNA-seq, protein and molecular docking, and Targeted Metabolomics (LC-MS), our data demonstrated that macrophages expressing TREM2 exhibited decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway after efferocytosis, which impaired NAD⁺ transport into mitochondria, downregulated SLC25A53 thereby causing the breakpoint in the TCA cycle and subsequently increased itaconate production. In vitro exper

SUBMITTER: Gong S 

PROVIDER: S-EPMC10850484 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature