Fig. 3

Metabolic reprogramming of macrophages after MI. In the early phase post myocardial infarction (MI), macrophages infiltrate the injured myocardium and secrete pro-inflammatory cytokines. Under hypoxic stimuli, there is a shift in their energy metabolism, favoring glycolysis through the pentose phosphate pathway (PPP). Additionally, there is rewiring of the tricarboxylic acid cycle (TCA) and an elevation in mitochondrial reactive oxygen species (mtROS) levels. As a result, substrate oxidation and adenosine triphosphate (ATP) synthesis via oxidative phosphorylation (OXPHOS) are reduced. In contrast, macrophages adopt a phagocytotic phenotype during the wound healing phase. This transition is driven by changes in the microenvironment, efferocytosis (the clearance of apoptotic cells), and further metabolic reprogramming. Consequently, macrophages switch back to oxidative metabolism and actively participate in collagen deposition, promoting tissue repair and healing processes. The balance between hypoxia-induced factor-1ɑ (HIF-1ɑ) and HIF-2ɑ is also involved in the metabolic reprogramming and phenotype switching of macrophages. HIF-1ɑ induces the conversion of I-arginine into inducible nitric oxide synthase (iNOS) while HIF-2 induces the production of arginase-1. Adapted from “Comparison Between Oxidative Eustress and Oxidative Distress”, by BioRender.com (2020). Retrieved from https://app.biorender.com/biorender-templates