Extended Data Fig. 10: Mechanical regulation of macrophage metabolism by Allograft Inflammatory Factor 1 (AIF1) leads to adverse remodeling after cardiac injury. | Nature Cardiovascular Research

Extended Data Fig. 10: Mechanical regulation of macrophage metabolism by Allograft Inflammatory Factor 1 (AIF1) leads to adverse remodeling after cardiac injury.

From: Mechanical regulation of macrophage metabolism by allograft inflammatory factor 1 leads to adverse remodeling after cardiac injury

Extended Data Fig. 10

Myocardial infarction leads to necrotic death of cardiomyocytes and release of damage associated molecular patterns (DAMPs). Recognition of DAMPs on macrophages by Toll-like Receptors (TLR), including TLR4, leads to calcium influx and activation of Allograft Inflammatory Factor 1 (AIF1). AIF1 interacts with RAC1 to promote actin polymerization and mechanical stiffness. This activates NADPH oxidase (NOX) and increases reactive oxygen species (ROS) production. Elevated ROS levels stabilize Hypoxia Inducible Factor (HIF)-1α, leading to its nuclear translocation and transcription of genes involved in glycolysis and inflammation. This switch to glycolytic metabolism fuels increased production of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which contribute to adverse left ventricular remodeling and progression to heart failure (HF).

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