Unveiling the lysosomal-cholesterol nexus: NCOA7’s pivotal role in pulmonary artery hypertension pathogenesis and therapy

Abstract

We read with great interest a recent study investigating the role of nuclear receptor coactivator 7 (NCOA7) as a critical regulator of lysosomal function, oxysterol, and bile acid metabolism, and its link to endothelial cells (ECs) inflammation and immune activation in pulmonary artery hypertension (PAH). The study demonstrated that NCOA7 deficiency exacerbated lysosomal dysfunction, leading to inflammatory sterol accumulation and immune activation, which subsequently triggers endothelial immune responses. Translationally, NCOA7 activation emerges as a promising therapeutic strategy, while plasma oxysterol and bile acid levels offer potential prognostic biomarkers for PAH severity and mortality.

Keywords

Pulmonary arterial hypertension / NCOA7 / lysosomal dysfunction / cholesterol metabolism / inflammation

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