Neutrophil Irgm1 ameliorates sepsis-induced myocardial dysfunction by promoting Alox15 degradation - PubMed
5 days ago
- #Ferroptosis
- #Neutrophil Irgm1
- #Sepsis-induced myocardial dysfunction
- Neutrophil Irgm1 plays a crucial role in ameliorating sepsis-induced myocardial dysfunction (SIMD).
- IRGM/Irgm1 expression is upregulated in SIMD patients' neutrophils and inversely correlates with disease severity.
- Neutrophil-specific Irgm1 deficiency worsens cardiac dysfunction and myocardial inflammation in mice.
- Irgm1 interacts with E3 ubiquitin ligase RNF213 to promote Alox15 ubiquitination and degradation.
- This mechanism inhibits neutrophil ferroptosis and reduces 15-HETE production, alleviating SIMD.
- Alox15 and 15-HETE levels in SIMD patients positively correlate with disease severity.
- PD146176, an Alox15-targeting drug, improves cardiac function in SIMD mice.
- Irgm1 may serve as a prognostic biomarker and therapeutic target for SIMD.