Essential role of protein kinase R in the pathogenesis of pulmonary veno-occlusive disease.

ABSTRACT: Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension, characterized by progressive remodeling of small pulmonary arteries and veins with no therapies. Using a mitomycin C-induced (MMC-induced) rat model, we previously demonstrated that protein kinase R-mediated (PKR-mediated) integrated stress response (ISR) drives endothelial dysfunction and vascular remodeling. To determine whether PKR is the primary mediator of ISR and the pathogenesis, we treated control (Ctrl) and PKR-knockout (KO) mice with the same dose of MMC. Consistent with rat data, Ctrl mice displayed ISR activation, vascular remodeling, and pulmonary hypertension after MMC treatment, while KO mice showed none of these phenotypes. Proteomic analysis revealed that MMC-mediated I

SUBMITTER: Prabhakar A 

PROVIDER: S-EPMC12513476 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature