Macrophage ferroptosis potentiates GCN2 deficiency induced pulmonary venous arterialization.

ABSTRACT: Pulmonary veno-occlusive disease (PVOD) is a fatal disease characterized by the remodelling of pulmonary veins and haemosiderin accumulation in macrophages. Although (General Control Nonderepressible 2) GCN2 deficiency has been reported in PVOD patients, the underlying mechanism by which GCN2 deficiency affects the pulmonary venous cells and the surrounding cells, remains unclear. Here, we perform immunohistochemistry and scRNA-sequencing analyses to show that macrophages are the major population affected by GCN2 deficiency and ferroptosis pathway-related genes are upregulated in lung macrophages of PVOD patients. Treatment with the specific ferroptosis inhibitor ferrostatin-1 (Fer-1) reverses the changes in haemodynamic indices observed in Eif2ak4^{K1488X/K1488X} hypoxia mice and

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12454641 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature