Irgm1 improves cardiac repair post-MI by promoting neutrophil clearance and efferocytosis; LOC14 reduces tissue damage and enhances recovery in Irgm1-deficient mice.
Does LOC14 administration or Irgm1 expression improve post-infarction cardiac repair and neutrophil clearance?
The Irgm1-PDIA3 axis is critical for post-MI cardiac repair by promoting neutrophil clearance, highlighting LOC14 as a potential therapeutic agent to enhance cardiac recovery.
Absolute Event Rate: 0% vs 0%
Delayed neutrophil clearance after myocardial infarction (MI) significantly disrupts the myocardial microenvironment, but the underlying mechanisms remain unclear. Macrophage-mediated efferocytosis of infiltrating neutrophils is crucial for resolving inflammation and restoring homeostasis post-MI. However, the specific regulatory mechanisms governing neutrophil clearance and efferocytosis remain undefined. This study demonstrates a significant correlation between increased IRGM expression in peripheral blood neutrophils of patients with MI and improved prognostic outcomes. Neutrophil-specific deletion of Irgm1 exacerbates cardiac dysfunction, impairs post-MI repair, and hinders neutrophil clearance and efferocytosis. Irgm1 deficiency further delays neutrophil clearance in the heart and extends neutrophil survival. Mechanistically, Irgm1 directly interacts with PDIA3, promoting its autophagic degradation, which in turn activates the endoplasmic reticulum stress/NF-κB/caspase-3 pathway to facilitate neutrophil clearance and efferocytosis. In vivo administration of LOC14 significantly reduces tissue damage and enhances cardiac recovery in neutrophil Irgm1-deficient mice post-MI. These findings highlight the pivotal role of the Irgm1-PDIA3 axis in facilitating cardiac repair post-MI by promoting neutrophil clearance. LOC14 may serve as a potential therapeutic agent to enhance cardiac function post-MI, particularly in Irgm1-deficient cases.
Wang et al. (Wed,) reported a other. Irgm1 improves cardiac repair post-MI by promoting neutrophil clearance and efferocytosis; LOC14 reduces tissue damage and enhances recovery in Irgm1-deficient mice.