Enhancing NAD+ Metabolome in Cardiovascular Diseases: Promises and Considerations

Jahan, Fahmida; Bagchi, Rushita A.

doi:10.3389/fcvm.2021.716989

Cited by 3 publications

(5 citation statements)

References 55 publications

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“…Encouragingly, there are many mouse models that have successfully managed to increase NAD + pools to combat heart failure ( 12 , 36 , 65 , 68 , 69 ). Overexpression of Nampt and supplementation with precursors NAM, NR, and NMN have already been demonstrated to improve cardiac function and defend against cardiac injury in several forms of heart disease ( 12 , 65 , 68 ). Unfortunately, the variability in disease states, examined parameters, and delivery strategies have prevented the conclusion of distinct, optimal treatment options.…”

Section: Nad + Supplementation Of the Heart In Car...mentioning

confidence: 99%

“…Unfortunately, the variability in disease states, examined parameters, and delivery strategies have prevented the conclusion of distinct, optimal treatment options. Often, the critical readout of actual NAD + levels has been left out of these studies, or the increase does not reach statistical significance, despite some clear effect on cardiac health ( 36 , 68 , 69 ). However, NAD + does not exert its myriad effects solely through presence.…”

Section: Nad + Supplementation Of the Heart In Car...mentioning

confidence: 99%

“…Intraperitoneal supplementation with NR in a nondisease state reduced Nmrk2 expression ( 72 ), which may explain why some heart studies were unable to elevate NAD + levels with NR in control mice ( 69 ). NMN is most often tried in mouse models with intraperitoneal injections, but toxicity quantities have not been evaluated sufficiently in humans ( 65 , 68 ).…”

Section: Nad + Supplementation Of the Heart In Car...mentioning

confidence: 99%

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Circadian cardiac NAD⁺ metabolism, from transcriptional regulation to healthy aging

Carpenter

Dierickx

2022

American Journal of Physiology-Cell Physiology

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Nicotinamide adenine dinucleotide (NAD+) is a critical redox factor and coenzyme with rhythmic availability, and reduced NAD+ levels are a common factor of many disease states, including risk factors associated with aging. Recent studies have expanded on the role of circadian rhythms and the core clock factors that maintain them in the regulation of NAD+ levels in the heart. This has revealed that NAD+ pools and their use are tightly linked to cardiac function, but also heart failure. The convergence of these fields, namely, clock regulation, heart disease, and NAD+ metabolism present a complex network ripe with potential scientific and clinical discoveries, given the growing number of animal models, recently developed technology, and opportunity for safe and accessible precursor supplementation. This review seeks to briefly present known information on circadian rhythms in the heart, connect that research to our understanding of cardiac NAD+ metabolism, and finally discuss potential future experiments to better understand interventional opportunities in cardiovascular health regarding these subjects.

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Section: Nad + Supplementation Of the Heart In Car...mentioning

confidence: 99%

Section: Nad + Supplementation Of the Heart In Car...mentioning

confidence: 99%

Section: Nad + Supplementation Of the Heart In Car...mentioning

confidence: 99%

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Circadian cardiac NAD⁺ metabolism, from transcriptional regulation to healthy aging

Carpenter

Dierickx

2022

American Journal of Physiology-Cell Physiology

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“…There is strong evidence to suggest that placental mitochondrial dysfunction may be a common feature across all PE subclasses [8], however a lack of subclass-specific research endeavours has limited our current understanding of this pathology, specifically in the context of inflammation-driven PE. In non-pregnant populations, several inflammatory disease conditions have been tightly linked to mitochondrial dysfunction, in large part driven by profound overactivity of nicotinamide adenine dinucleotide (NAD + ) consuming enzymes, leading to depletion of intracellular NAD + stores [16][17][18][19][20][21][22][23][24][25][26][27][28]. In the current study, this body of work will be expanded to determine if NAD + depletion may likewise initiate placental mitochondrial dysfunction in inflammation-mediated PE.…”

Section: Introductionmentioning

confidence: 99%

NAD⁺depletion and altered mitochondrial function are key to the establishment of placental dysfunction in an inflammatory-driven subclass of preeclampsia

Jahan,

Vasam,

Cariaco

et al. 2023

Preprint

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Preeclampsia (PE) is a pregnancy associated hypertensive disease. It is one of the major causes of pregnancy-related maternal/perinatal adverse health outcomes, with a lack of highly effective preventative strategies and/or therapeutic interventions. Our group has previously identified distinct subclasses of pathophysiology underlying a PE diagnosis, one of which exhibits heightened immune activation at the gestational parent-fetal interface, identified as inflammatory-driven PE. In non-pregnant populations, chronic inflammation is associated with reduced cellular availability of NAD+, a vitamin B3-derived metabolite involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammatory-driven PE, we observed increased activity of NAD+-consuming PARP enzymes and reduced NAD+content. Moreover, these placentas had decreased expression of several mitochondrial oxidative phosphorylation (OXPHOS) proteins and evidence of oxidative damage. This human data was supported by cell culture findings, which likewise demonstrated increased PARP activity, coupled to decreased mitochondrial respiration rates and decreased invasive function of cultured HTR8 human trophoblast cells, following inflammatory induction by TNF-α. Importantly, these adverse inflammatory effects were attenuated by boosting cellular NAD+levels with nicotinamide riboside (NR). Finally, using an LPS-induced rodent model of inflammatory-driven PE, we demonstrated that NR administration (200mg/kg/day) from gestational day (GD) 1-19 could prevent the development of maternal hypertension and fetal/placental growth restriction, improve placental mitochondrial function, reduce placental inflammation and oxidative stress. Thus, this study demonstrates the critical role of NAD+metabolism in maintaining healthy placental function and identifies NAD+boosting as a promising preventative strategy for the inflammatory-driven subclass of PE.One sentence summaryBoosting NAD+levels prevent inflammatory-driven preeclampsia by improving placental mitochondrial function.

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“…Owing to its centrality and far-ranging influence in the cell, perturbations to NAD + homeostasis are associated with a considerable and diverse number of diseases, including various metabolic disorders [7], neurological disorders [8], cardiovascular disease [9], and numerous cancers [10][11][12]. Supplementation of NAD + precursors has been shown to be efficacious in treating or alleviating symptoms of several diseases [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The Histone Deacetylases Hst1 and Rpd3 Integrate De Novo NAD+ Metabolism with Phosphate Sensing in Saccharomyces cerevisiae

Groth

Lee

Huang

et al. 2023

IJMS

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Nicotinamide adenine dinucleotide (NAD+) is a critical cofactor essential for various cellular processes. Abnormalities in NAD+ metabolism have also been associated with a number of metabolic disorders. The regulation and interconnection of NAD+ metabolic pathways are not yet completely understood. By employing an NAD+ intermediate-specific genetic system established in the model organism S. cerevisiae, we show that histone deacetylases (HDACs) Hst1 and Rpd3 link the regulation of the de novo NAD+ metabolism-mediating BNA genes with certain aspects of the phosphate (Pi)-sensing PHO pathway. Our genetic and gene expression studies suggest that the Bas1–Pho2 and Pho2–Pho4 transcription activator complexes play a role in this co-regulation. Our results suggest a model in which competition for Pho2 usage between the BNA-activating Bas1–Pho2 complex and the PHO-activating Pho2–Pho4 complex helps balance de novo activity with PHO activity in response to NAD+ or phosphate depletion. Interestingly, both the Bas1–Pho2 and Pho2–Pho4 complexes appear to also regulate the expression of the salvage-mediating PNC1 gene negatively. These results suggest a mechanism for the inverse regulation between the NAD+ salvage pathways and the de novo pathway observed in our genetic models. Our findings help provide a molecular basis for the complex interplay of two different aspects of cellular metabolism.

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Enhancing NAD+ Metabolome in Cardiovascular Diseases: Promises and Considerations

Cited by 3 publications

References 55 publications

Circadian cardiac NAD⁺ metabolism, from transcriptional regulation to healthy aging

Circadian cardiac NAD⁺ metabolism, from transcriptional regulation to healthy aging

NAD⁺depletion and altered mitochondrial function are key to the establishment of placental dysfunction in an inflammatory-driven subclass of preeclampsia

The Histone Deacetylases Hst1 and Rpd3 Integrate De Novo NAD+ Metabolism with Phosphate Sensing in Saccharomyces cerevisiae

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Enhancing NAD+ Metabolome in Cardiovascular Diseases: Promises and Considerations

Cited by 3 publications

References 55 publications

Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging

Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging

NAD+depletion and altered mitochondrial function are key to the establishment of placental dysfunction in an inflammatory-driven subclass of preeclampsia

The Histone Deacetylases Hst1 and Rpd3 Integrate De Novo NAD+ Metabolism with Phosphate Sensing in Saccharomyces cerevisiae

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Product

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Circadian cardiac NAD⁺ metabolism, from transcriptional regulation to healthy aging

Circadian cardiac NAD⁺ metabolism, from transcriptional regulation to healthy aging

NAD⁺depletion and altered mitochondrial function are key to the establishment of placental dysfunction in an inflammatory-driven subclass of preeclampsia