Loss of Type 2 Bone Morphogenetic Protein Receptor Activates NOD‐Like Receptor Family Protein 3/Gasdermin E‐Mediated Pyroptosis in Pulmonary Arterial Hypertension

• DOI: 10.1161/jaha.124.034726
• Publication Date: 2025-01-23T11:15:00Z
• Authors: Xiao‐ting Tian; Zhou‐yang‐fan Peng; Yu‐si Wu; Yuan‐yuan Cao; Xue‐chun Li; Ying Li; Si‐Yuan Tang; Alex F. Chen; Xiao‐hui Li
• Keywords: Pyroptosis

Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary remodeling, resulting in elevated pressure right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway endothelium inclined prompt PAH models, but the underlying mechanism BMPR2 deficiency-mediated needs further investigation. This study was designed investigate whether deficiency contributes via NLRP3 (NOD-like family 3)/GSDME (gasdermin E)-mediated pyroptosis pathway. knockout or short hairpin RNA interference GSDME performed animal models its effect on progression. In addition, effects restoration BMP9 (bone 9) FK506 were explored both cell models. Knockout can alleviate development pyroptosis, accompanied with improved integrity, ventricular systolic pressure. Blocking sufficient induce upregulation release inflammatory factor IL-1β (interleukin-1β) cells. Moreover, GSDME-mediated through activation whereas reverse these phenotypes. These findings provide evidence loss promotes enhancing NLRP3/GSDME PAH. Our may new insights explore treatment.