What question did this study set out to answer?

The study aims to investigate the effects of NAMPT-overexpressing exosomes on aortic stenosis and their underlying mechanisms.

January 10, 2026International Journal of Molecular Sciences0 citationsOpen Access

Exosomal NAMPT from Engineered Mesenchymal Stem Cells Mitigates Aortic Stenosis via Metabolic and Anti-Inflammatory Pathways

Q: What does this research mean for the field?

NAMPT-enriched MSC-derived exosomes significantly reduce aortic valve peak velocity and valvular thickening in aortic stenosis mice. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

DKDipan KunduUNSW Sydney MKMatthew KiedrowskiNortheast Ohio Medical University JGJames GaddNortheast Ohio Medical University

Key Result

NAMPT-enriched MSC-derived exosomes significantly reduced aortic valve peak velocity and valvular thickening in aortic stenosis mice.

Key Points

The study aims to investigate the effects of NAMPT-overexpressing exosomes on aortic stenosis and their underlying mechanisms.
Used AS mouse model for treatment with NAMPT-Exo, MSC-Exo, or PBS.
Conducted echocardiography and histological examination after treatment.
Analyzed miRNA expression in cardiac endothelial cells from treated and untreated mice.
Investigated EndMT occurrence in aortic valves.
NAMPT-Exo treatment reduced aortic valve peak velocity and valvular thickening.
Improved heart function was observed with enhanced ejection fraction and fractional shortening.
Redistribution of miR-146a-3p levels was noted in treated AS hearts.
EndMT in aortic valves was lessened by NAMPT-Exo treatment.
In vitro studies indicated that inhibiting miR-146a-3p can suppress EndMT.

Structured PICO

Does treatment with NAMPT-enriched MSC-derived exosomes reduce aortic stenosis progression in a mouse model?

Population

Six-week-old EC CXCR4 KO (AS) mice

Intervention

Weekly injections of exosomes from NAMPT-overexpressing mesenchymal stem cells (NAMPT-Exo) for three weeks

Comparator

MSC-Exo or PBS

Outcome

Aortic valve peak velocity, valvular thickening, and microcalcificationssurrogate

NAMPT-enriched MSC-derived exosomes slow the progression of aortic stenosis in a mouse model by mitigating endothelial-to-mesenchymal transition via miR-146a-3p regulation.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

The aim of this study was to determine whether exosomes from Nicotinamide phosphoribosyltransferase (NAMPT)-overexpressing mesenchymal stem cells (MSC NAMPT-Exo) can attenuate aortic stenosis (AS) and explored the underlying mechanism. NAMPT expression was examined in EC CXCR4 KO (AS) mouse hearts. Six-week-old AS mice received weekly injections of NAMPT-Exo, MSC-Exo, or PBS for three weeks, followed by echocardiography and histological examination of the valves (H&E, Alizarin Red, immunofluorescence). Cardiac ECs from control, AS, and NAMPT-Exo-treated mice were analyzed for miRNA expression (miR-146a-3p/5p, miR-125b-5p, miR-142a-5p). NAMPT expression was decreased in AS hearts. Treatment with NAMPT-Exo reduced aortic valve peak velocity, valvular thickening, and microcalcifications, while improving ejection fraction, fractional shortening, and ventricular dimensions. AS endothelial cells showed elevated levels of miR-146a-3p, miR-146a-5p, and miR-142a-5p, NAMPT-Exo specifically normalized miR-146a-3p. Histology revealed EndMT in AS valves, which was diminished by NAMPT-Exo. In vitro, inhibiting miR-146a-3p suppressed TGF-β-induced EndMT. Our results demonstrate that NAMPT-enriched MSC-derived exosomes effectively slow the progression of AS. Additionally, our findings highlight miR-146a-3p as a key regulator of EndMT, suggesting it as a potential molecular target for future therapies.

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