Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro cell culture and ex vivo animal tissue study
PubMed 32389638 · doi:10.1016/j.bcp.2020.114019
What was done
Human aortic endothelial cells (HAECs) stimulated with IL-1β or TNF-α were treated with nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) to evaluate inflammatory markers (ICAM1, vWF), intracellular NAD content, and NAD-metabolizing enzyme expression (NAMPT, CD38, CD73). Ex vivo aortic rings from wild-type and CD73-deficient mice were exposed to angiotensin II to assess nitric oxide-dependent vasorelaxation. The necessity of CD73 was evaluated using the pharmacological inhibitor AOPCP and CD73-knockout mice.
What was found
Both NMN and NR reduced ICAM1 and vWF expression and increased intracellular NAD in cytokine-stimulated HAECs after 24 hours. The CD73 inhibitor AOPCP blocked NMN-induced anti-inflammatory effects and NAD elevation, while NR effects were unaffected. In ex vivo aortic rings, both NMN and NR prevented angiotensin II-induced impairment of acetylcholine-mediated vasorelaxation. In CD73-knockout aortic rings, the protective effect of NMN was abolished, whereas the effect of NR was preserved. The abstract reported directions of effect but did not provide exact numerical values.
Why it matters
The findings demonstrate that exogenous NMN requires extracellular conversion to NR by endothelial CD73 to support intracellular NAD synthesis and preserve vascular endothelial function, clarifying distinct uptake mechanisms between NMN and NR.
Limits
The study is entirely preclinical, relying on cultured human cells and ex vivo mouse vascular tissue without in vivo pharmacokinetic or human clinical trial validation. Exact sample sizes, statistical variance, and quantitative effect magnitudes were omitted from the abstract.
Cited by
- supports Research indicates that nicotinamide riboside (NR) converts to NAD+ within cells more readily than nicotinamide mononucleotide (NMN).