ENAMPT/TLR4 signaling drives PAH cellular phenotypic switching and lung vascular remodeling.

ABSTRACT:

Background

The attenuation of cellular phenotypic switchingdriving PAH vascular remodeling remains an unmet therapeutic need. As eNAMPT (nicotinamide phosphoribosyltransferase)/TLR4 signaling significantly contributes to PH pathobiology, an eNAMPT-neutralizing ALT-100 mAb was utilized to rescue monocrotaline (MCT) and hypoxia/Sugen (Hy/Su) preclinical PH rat models and to evaluate eNAMPT/TLR4 involvement in endothelial cell (EC), smooth muscle cell (SMC) and monocyte/macrophage phenotypic switching.

Methods

MCT-PH or Hy/Su-PH rats received IgG or ALT-100 mAb (subQ, beginning week 4) with measurements of PH severity and lung tissue scRNAseq at day 42.

Results

PH severity indices (hemodynamic, histologic, vascular remodeling) were significantly attenuated in MCT-PH and

SUBMITTER: Ahmed M 

PROVIDER: S-EPMC12573901 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature