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NAD + Metabolism in Cardiac Health, Aging, and Disease
Nicotinamide adenine dinucleotide (NAD ) is a central metabolite involved in energy and redox homeostasis as well as in DNA repair and protein deacetylation reactions. Pharmacological or genetic inhibition of NAD -degrading enzymes, external supplementation of NAD precursors, and transgenic overexpr...
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Published in: | Circulation (New York, N.Y.) N.Y.), 2021-11, Vol.144 (22), p.1795-1817 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Nicotinamide adenine dinucleotide (NAD
) is a central metabolite involved in energy and redox homeostasis as well as in DNA repair and protein deacetylation reactions. Pharmacological or genetic inhibition of NAD
-degrading enzymes, external supplementation of NAD
precursors, and transgenic overexpression of NAD
-generating enzymes have wide positive effects on metabolic health and age-associated diseases. NAD
pools tend to decline with normal aging, obesity, and hypertension, which are all major risk factors for cardiovascular disease, and NAD
replenishment extends healthspan, avoids metabolic syndrome, and reduces blood pressure in preclinical models. In addition, experimental elevation of NAD
improves atherosclerosis, ischemic, diabetic, arrhythmogenic, hypertrophic, or dilated cardiomyopathies, as well as different modalities of heart failure. Here, we critically discuss cardiomyocyte-specific circuitries of NAD
metabolism, comparatively evaluate distinct NAD
precursors for their preclinical efficacy, and raise outstanding questions on the optimal design of clinical trials in which NAD
replenishment or supraphysiological NAD
elevations are assessed for the prevention or treatment of major cardiac diseases. We surmise that patients with hitherto intractable cardiac diseases such as heart failure with preserved ejection fraction may profit from the administration of NAD
precursors. The development of such NAD
-centered treatments will rely on technological and conceptual progress on the fine regulation of NAD
metabolism. |
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ISSN: | 0009-7322 1524-4539 |
DOI: | 10.1161/CIRCULATIONAHA.121.056589 |