Key result
Targeting NF-κB shows promise for reversing vascular remodeling and RV failure in PAH.
Why the study?
Current PAH therapies have limited efficacy in reversing established vascular remodeling, and controversies remain regarding the mechanisms, efficacy, and risks of targeting the NF-κB pathway.
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Targeting the NF-κB signaling pathway offers a promising therapeutic strategy for pulmonary arterial hypertension by addressing the underlying vascular remodeling and inflammation.
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.
He et al. (2026) conducted a review in Pulmonary arterial hypertension (PAH). NF-κB pathway modulators was evaluated. The NF-κB signaling pathway acts as a central inflammatory node in pulmonary arterial hypertension, and targeting it offers a promising strategy to reverse vascular remodeling and right heart failure.