TY  - JOUR
T1  - NAMPT-Driven Macrophage Polarization Regulates Smooth Muscle Cell Plasticity in Pulmonary Arterial Hypertension
A1  - Pieter Botha
A1  - Anel Van Wyk
A1  - Johan Marais
JF  - Interdisciplinary Research in Medical Sciences Specialty
JO  - Interdiscip Res Med Sci Spec
SN  - 3062-4401
Y1  - 2026
VL  - 6
IS  - 1
DO  - 10.51847/1Qpu3bcA3T
SP  - 178
EP  - 193
N2  - Phenotypic modulation of smooth muscle cells (SMC) constitutes a central mechanism contributing to the development of pulmonary arterial hypertension (PAH). Despite its importance, the regulatory pathways involved are not yet fully understood. In this study, single-cell RNA sequencing was applied to pulmonary arterial tissues procured from lung transplant recipients to characterize cellular diversity and the transcriptomic signatures of major cell populations. Three separate SMC subpopulations were distinguished: contractile, fibroblast-like, and chondroid-like. Both trajectory inference and in vitro validation demonstrated a pronounced shift from the contractile toward the fibroblast-like phenotype in PAH. Intercellular communication analysis further uncovered classical (M1) macrophage polarization together with intensified pro-inflammatory interactions between macrophages and SMCs in diseased tissue. Nicotinamide phosphoribosyltransferase (NAMPT) was highlighted as a critical mediator of macrophage polarization. In Sugen/hypoxia (Su/Hx)-induced PAH mouse models, macrophages displayed upregulated Nampt expression, while its inhibition markedly reduced pro-inflammatory cytokine release. In co-culture experiments, targeted knockdown of Nampt in macrophages effectively prevented the transition of SMCs to a fibroblast-like state. Moreover, Ccl2/5 was identified as an essential cytokine driving SMC phenotypic changes. Taken together, this work provides a detailed cellular map of healthy human pulmonary arteries and establishes that NAMPT-orchestrated M1 macrophage polarization drives fibroblast-like phenotypic switching of SMCs through CCR2/CCR5-dependent intercellular signaling in PAH.
UR  - https://galaxypub.co/article/nampt-driven-macrophage-polarization-regulates-smooth-muscle-cell-plasticity-in-pulmonary-arterial-h-1wfwpqbenysm1xb
ER  -