Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb 4;12(2):376.
doi: 10.3390/antiox12020376.

NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health

Affiliations
Review

NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health

Roberto Campagna et al. Antioxidants (Basel). .

Abstract

Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous metabolite that takes part in many key redox reactions. NAD+ biosynthesis and NAD+-consuming enzymes have been attracting markedly increasing interest since they have been demonstrated to be involved in several crucial biological pathways, impacting genes transcription, cellular signaling, and cell cycle regulation. As a consequence, many pathological conditions are associated with an impairment of intracellular NAD+ levels, directly or indirectly, which include cardiovascular diseases, obesity, neurodegenerative diseases, cancer, and aging. In this review, we describe the general pathways involved in the NAD+ biosynthesis starting from the different precursors, analyzing the actual state-of-art of the administration of NAD+ precursors or blocking NAD+-dependent enzymes as strategies to increase the intracellular NAD+ levels or to counteract the decline in NAD+ levels associated with ageing. Subsequently, we focus on the disease-related and age-related alterations of NAD+ homeostasis and NAD+-dependent enzymes in endothelium and the consequent vascular dysfunction, which significantly contributes to a wide group of pathological disorders.

Keywords: NAD+; NNMT; PARP1; SIRT1; endothelium; nicotinamide adenine dinucleotide; vascular health.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pathways of NAD+ biosynthesis and major NAD+-consuming enzymes. The Preiss–Handler pathway is highlighted in green; the de novo biosynthesis pathway is in blue; the NAD+ salvage pathway is in yellow.
Figure 2
Figure 2
Impact of NAD+ homeostasis and major NAD+-consuming enzymes on vascular health.

Similar articles

Cited by

References

    1. Rajman L., Chwalek K., Sinclair D.A. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27:529–547. doi: 10.1016/j.cmet.2018.02.011. - DOI - PMC - PubMed
    1. Zapata-Perez R., Wanders R.J.A., van Karnebeek C.D.M., Houtkooper R.H. NAD+ homeostasis in human health and disease. EMBO Mol. Med. 2021;13:e13943. doi: 10.15252/emmm.202113943. - DOI - PMC - PubMed
    1. D’Amours D., Desnoyers S., D’Silva I., Poirier G.G. Poly(ADP-ribosyl) ation reactions in the regulation of nuclear functions. Pt 2Biochem. J. 1999;342:249–268. doi: 10.1042/bj3420249. - DOI - PMC - PubMed
    1. Bogan K.L., Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: A molecular evaluation of NAD+ pre-cursor vitamins in human nutrition. Annu. Rev. Nutr. 2008;28:115–130. doi: 10.1146/annurev.nutr.28.061807.155443. - DOI - PubMed
    1. Chu X., Raju R.P. Regulation of NAD+ metabolism in aging and disease. Metabolism. 2021;126:154923. doi: 10.1016/j.metabol.2021.154923. - DOI - PMC - PubMed

Grants and funding

This research received no external funding.