Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside

Mateuszuk, Łukasz; Campagna, Roberto; Kutryb–Zajac, Barbara; Kuś, Kamil; Słomińska, Ewa M.; Smolenski, Ryszard T.; Chłopicki, Stefan

doi:10.1016/j.bcp.2020.114019

Cited by 61 publications

(48 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NMN synthesis via NR inhibits endothelial in ammation and improves NO-dependent function. Activation of endothelial SIRT1 controls endothelial homeostasis and vascular functionality by modulating the activity of endothelial nitric oxide synthase (eNOS), p53, angiotensin II receptor (Ang II), FOXO1 and other mechanisms [94] Additionally, the question arises about the method of administration of NR to patients undergoing chemotherapy. As indicated in the previous chapters, the drug is often administered orally and the same doses intraperitoneally (not possible in humans).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects.

Podyacheva

Toropova

2021

Preprint

View full text Add to dashboard Cite

Despite the progress in the development of new anticancer strategies, cancer is rapidly spreading around the world and remains one of the most common diseases. At the same time, oncological diseases are detected in patients with late stages of the course in the overwhelming majority of cases. This fact necessitates chemotherapy both as part of a combination and in the view of an independent form of treatment. For more than 40 years, doxorubicin has been widely used in the treatment of solid and hematological tumors. At the same time, the problem of its cardiotoxicity remains unresolved, despite the high efficiency of this drug. Symptomatic therapy is used as a treatment for side-effects of doxorubicin or pathological conditions that have already appeared on their background. To date, there are no treatment methods for doxorubicin cardiomyopathy as such. A drug such as nicotinamide riboside can play an important role in solving this problem. Nicotinamide riboside is a pyridine nucleoside similar to vitamin B3 that acts as a precursor to NAD+. There are no such works in cardiomyopathy, despite the abundance of works devoted to the mechanisms of realization of the effects of nicotinamide riboside in various pathologies. The review analyzes information about the effects of NR on various experimental models of pathologies, its role in the synthesis of NAD+, and also considers the possibility and prospects of its use for the prevention of doxorubicin cardiomyopathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Consent For Publicationmentioning

confidence: 99%

Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects.

Podyacheva

Toropova

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As to • NO production, the abilities to ameliorate the ageassociated functional impairments of the endothelium have been demonstrated for all agents featured in Figure 3: metformin (Triggle et al, 2020), resveratrol and other polyphenols (Oak et al, 2018;Li et al, 2019), NAR (Mateuszuk et al, 2020), sulforafan (Matsui et al, 2016), carnosine (Takahashi et al, 2009), antioxidants (Wray et al, 2012), spermidine (Ahrendt et al, 2020), melatonin (Rodella et al, 2013;Salmanoglu et al, 2016), and rapamycin, the effects of the latter being controversial (Reineke et al, 2015). This common property of such a diverse group of agents contributes to their common ability to ameliorate the consequences of aging, in particular, decreases in the functional reserves, including those mobilized in response to COVID-19.…”

Section: Pathophysiological Implicationsmentioning

confidence: 97%

COVID-19: A Challenge to Physiology of Aging

Golubev

2020

Front. Physiol.

View full text Add to dashboard Cite

The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. COVID-19 case fatality rate (CFR) increases with age exponentially, its doubling time being about 7 years, irrespective of countries and epidemic stages. The same age-dependent mortality pattern known as the Gompertz law is featured by the total mortality and its main constituents attributed to cardiovascular, metabolic, neurological, and oncological diseases. Among patients dying of COVID-19, most have at least one of these conditions, whereas none is found in most of those who pass it successfully. Thus, gerontology is indispensable in dealing with the pandemic, which becomes a benchmark for validating the gerontological concepts and advances. The two basic alternative gerontological concepts imply that either aging results from the accumulation of stochastic damage, or is programmed. Based on these different grounds, several putative anti-aging drugs have been proposed as adjuvant means for COVID-19 prevention and/or treatment. These proposals are reviewed in the context of attributing the molecular targets of these drugs to the signaling pathways between the sensors of resource availability and the molecular mechanisms that allocate resources to storage, growth and reproduction or to self-maintenance and repair. Each of the drugs appears to reproduce only a part of the physiological responses to reduced resource availability caused by either dietary calories restriction or physical activity promotion, which are the most robust means of mitigating the adverse manifestations of aging. In the pathophysiological terms, the conditions of the endothelium, which worsen as age increases and may be significantly improved by the physical activity, is a common limiting factor for the abilities to withstand both physical stresses and challenges imposed by COVID-19. However, the current anti-epidemic measures promote sedentary indoor lifestyles, at odds with the most efficient behavioral interventions known to decrease the vulnerability to both the severe forms of COVID-19 and the prevalent aging-associated diseases. To achieve a proper balance in public health approaches to COVID-19, gerontologists should be involved in crosstalk between virologists, therapists, epidemiologists, and policy makers. The present publication suggests a conceptual background for that.

show abstract

“…For example, administration of NR in food fully attenuated the increases in DNA damage, endothelial senescence, and lesion formation mediated by Snhg12 knockdown in the vessel wall in a mouse model of atherosclerosis ( Haemmig et al, 2020 ). In a recent preclinical study, NR was shown to inhibit endothelial inflammation, promote NO-mediated vasodilation, and prevent Ang II-induced endothelial dysfunction ( Mateuszuk et al, 2020 ). Atherosclerosis continue to claim millions of lives annually, and endothelial dysfunction and inflammation play an important role in the initiation and progression of atherosclerosis.…”

Section: Anti-senescent Therapies Targeting the Vascular Endotheliummentioning

confidence: 99%

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities

Sun

Feinberg

2021

Front. Physiol.

View full text Add to dashboard Cite

Cellular senescence is a stable form of cell cycle arrest in response to various stressors. While it serves as an endogenous pro-resolving mechanism, detrimental effects ensue when it is dysregulated. In this review, we introduce recent advances for cellular senescence and inflammaging, the underlying mechanisms for the reduction of nicotinamide adenine dinucleotide in tissues during aging, new knowledge learned from p16 reporter mice, and the development of machine learning algorithms in cellular senescence. We focus on pathobiological insights underlying cellular senescence of the vascular endothelium, a critical interface between blood and all tissues. Common causes and hallmarks of endothelial senescence are highlighted as well as recent advances in endothelial senescence. The regulation of cellular senescence involves multiple mechanistic layers involving chromatin, DNA, RNA, and protein levels. New targets are discussed including the roles of long noncoding RNAs in regulating endothelial cellular senescence. Emerging small molecules are highlighted that have anti-aging or anti-senescence effects in age-related diseases and impact homeostatic control of the vascular endothelium. Lastly, challenges and future directions are discussed including heterogeneity of endothelial cells and endothelial senescence, senescent markers and detection of senescent endothelial cells, evolutionary differences for immune surveillance in mice and humans, and long noncoding RNAs as therapeutic targets in attenuating cellular senescence. Accumulating studies indicate that cellular senescence is reversible. A better understanding of endothelial cellular senescence through lifestyle and pharmacological interventions holds promise to foster a new frontier in the management of cardiovascular disease risk.

show abstract

Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside

Cited by 61 publications

References 62 publications

Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects.

Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects.

COVID-19: A Challenge to Physiology of Aging

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities

Contact Info

Product

Resources

About