NF-κB signaling as a critical inflammatory node in pulmonary arterial hypertension: from vascular remodeling to right...

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling, leading to hemodynamic impairment and right heart dysfunction, and ultimately right heart failure and death. Despite advances in understanding its pathogenesis, PAH remains associated with poor prognosis and high mortality compared with other respiratory diseases, posing a significant global health burden. Current therapies primarily target the endothelin, nitric oxide, and prostacyclin pathways to achieve vasodilation and symptomatic relief; however, they have limited efficacy in reversing established vascular remodeling. The nuclear factor-κB (NF-κB) signaling pathway, a central regulator of inflammation and immune responses, plays a critical role in pulmonary vascular remodeling and endothelial-to-mesenchymal transition (EndMT). Targeting NF-κB has therefore emerged as a promising therapeutic strategy for PAH. Nevertheless, controversies remain regarding its mechanisms, therapeutic efficacy, and potential risks, particularly in combination strategies. This review summarizes current understanding of PAH pathogenesis and recent advances in targeting the NF-κB pathway.