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NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension

Yumin Qiu, Shiyue Xu, Xi Chen, Xing Wu, Zhe Zhou, Jianning Zhang, Qiang Tu, Bing Dong, Zhefu Liu, Jiang He, Xiaoyu Zhang, Shuangshuang Liu, Chen Su, Hui Huang, Wenhao Xia, Jun Tao
Signal Transduction and Targeted Therapy 2023 8:353

Bibliography

PubMed
PMID 37718359
PubMed Central
PMC10505611
DOI
10.1038/s41392-023-01577-3
Funding
Supported by the National Key Research and Development Program of China (2020YFC2008000), Guangzhou Key-Area Research and Development Program (202206080004), National Natural Science Foundation of China grants 82270460, 92249304, 82270458, 82000461, 82270429 and 82000466, and Kelin Star R08019.
Competing interests
The authors reported no competing interests.

Study snapshot

DesignMixed mechanistic paper with a small randomized open-label controlled human NMN intervention plus animal and cellular experiments.
ModelAdults with mild essential hypertension; mechanistic mouse and cell models were also studied.
Sample21 patients with mild essential hypertension were randomized; two withdrew, leaving 19 completers (9 NMN plus lifestyle modification, 10 lifestyle modification alone).
InterventionNMN 800 mg/day plus lifestyle intervention versus lifestyle intervention alone.
DurationThe randomized intervention was described as a 30-day treatment, with outcomes presented through approximately 6 weeks.
EndpointsBlood pressure; Vascular/endothelial function; PBMC NAD+; CD38-related mechanistic markers

What the study showed, in plain terms

This paper linked low NAD+ and higher CD38 activity with vascular dysfunction in hypertension, then tested whether NMN could modify that phenotype in a small human randomized study.

Nineteen participants were randomized to lifestyle intervention alone or lifestyle plus 800 mg/day NMN for six weeks. The NMN arm showed lower blood pressure and improved vascular-function measures, but the study was open-label and extremely small. Much of the mechanistic evidence comes from mouse and cell experiments.

Key findings

  • Hypertensive participants showed lower NAD+ measures associated with vascular dysfunction.
  • In the small randomized human arm, NMN plus lifestyle intervention reduced blood pressure and improved vascular-function measures relative to lifestyle control.
  • The paper proposed endothelial CD38 upregulation as a mechanism contributing to NAD+ depletion and vascular injury.
  • Mechanistic causality was supported mainly by animal and cellular experiments rather than the human intervention.

What this study can and cannot tell us

The human randomized component was very small: 21 participants were randomized and 19 completed. It was open-label and compared lifestyle modification plus NMN with lifestyle modification alone. The paper also combines human, animal and cellular experiments, so mechanistic findings from nonhuman systems should not be presented as directly demonstrated human mechanisms.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology