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NAD+ and Vascular Dysfunction: From Mechanisms to Therapeutic Opportunities

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Nicotinamide adenine dinucleotide (NAD+) is an essential and pleiotropic coenzyme involved not only in cellular energy metabolism, but also in cell signaling, epigenetic regulation, and post-translational protein modifications. Vascular disease risk factors are associated with aberrant NAD+ metabolism. Conversely, the therapeutic increase of NAD+ levels through the administration of NAD+ precursors or inhibitors of NAD+-consuming enzymes reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular pathologies. As such, NAD+ has emerged as a potential target for combatting age-related cardiovascular and cerebrovascular disorders. This review discusses NAD+-regulated mechanisms critical for vascular health and summarizes new advances in NAD+ research directly related to vascular aging and disease, including hypertension, atherosclerosis, coronary artery disease, and aortic aneurysms. Finally, we enumerate challenges and opportunities for NAD+ repletion therapy while anticipating the future of this exciting research field, which will have a major impact on vascular medicine.

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential and pleiotropic coenzyme involved not only in cellular energy metabolism, but also in cell signaling, epigenetic regulation, and post-translational protein modifications. Vascular disease risk factors are associated with aberrant NAD+ metabolism. Conversely, the therapeutic increase of NAD+ levels through the administration of NAD+ precursors or inhibitors of NAD+-consuming enzymes reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular pathologies. As such, NAD+ has emerged as a potential target for combatting age-related cardiovascular and cerebrovascular disorders. This review discusses NAD+-regulated mechanisms critical for vascular health and summarizes new advances in NAD+ research directly related to vascular aging and disease, including hypertension, atherosclerosis, coronary artery disease, and aortic aneurysms. Finally, we enumerate challenges and opportunities for NAD+ repletion therapy while anticipating the future of this exciting research field, which will have a major impact on vascular medicine.

참고문헌 (133)

  1. Roth GA, "Global burden of cardiovascular diseases and risk factors, 1990-2019 : update from the GBD 2019 Study", J Am Coll Cardiol, 76, pp.2982~3021 (2020)
  2. GBD 2019 Stroke Collaborators, "Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019", Lancet Neurol, 20, pp.795~820 (2021)
  3. López-Otín C, "Hallmarks of health", Cell, 184, pp.33~63 (2021)
  4. Verdin E, "NAD+ in aging, metabolism, and neurodegeneration", Science, 350, pp.1208~1213 (2015)
  5. Abdellatif M, "NAD+ metabolism in cardiac health, aging, and disease", Circulation, 144, pp.1795~1817 (2021)
  6. Yoshino J, "NAD+ intermediates : the biology and therapeutic potential of NMN and NR", Cell Metab, 27, pp.513~528 (2018)
  7. Csiszar A, "Role of endothelial NAD+deficiency in age-related vascular dysfunction", Am J Physiol Heart Circ Physiol, 316, pp.H1253~H1266 (2019)
  8. Das A, "Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging", Cell, 173, pp.74~89 (2018)
  9. Kane AE, "Sirtuins and NAD+ in the development and treatment of metabolic and cardiovascular diseases", Circ Res, 123, pp.868~885 (2018)
  10. Mitchell SJ, "Nicotinamide improves aspects of healthspan, but not lifespan, in mice", Cell Metab, 27, pp.667~676 (2018)
  11. Buqué A, "Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer", Nat Commun, 11, pp.3819~ (2020)
  12. Zhang YJ, "NAD+ administration decreases microvascular damage following cardiac ischemia", reperfusion by restoring autophagic flux, 2020, pp.115, 57~
  13. Chini CC, "Evolving concepts in NAD+ metabolism", Cell Metab, 33, pp.1076~1087 (2021)
  14. Covarrubias AJ, "NAD+ metabolism and its roles in cellular processes during ageing", Nat Rev Mol Cell Biol, 22, pp.119~141 (2021)
  15. Katsyuba E, "NAD+ homeostasis in health and disease", Nat Metab, 2, pp.9~31 (2020)
  16. Reiten OK, "Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing", Mech Ageing Dev, 199, pp.111567~ (2021)
  17. Ferrucci L, "Inflammageing : chronic inflammation in ageing, cardiovascular disease, and frailty", Nat Rev Cardiol, 15, pp.505~522 (2018)
  18. Furman D, "Chronic inflammation in the etiology of disease across the life span", Nat Med, 25, pp.1822~1832 (2019)
  19. Covarrubias AJ, "Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages", Nat Metab, 2, pp.1265~1283 (2020)
  20. Aksoy P, "Regulation of intracellular levels of NAD : a novel role for CD38", Biochem Biophys Res Commun, 345, pp.1386~1392 (2006)
  21. Boslett J, "Characterization of CD38 in the major cell types of the heart : endothelial cells highly express CD38 with activation by hypoxia-reoxygenation triggering NAD(P)H depletion", Am J Physiol Cell Physiol, 314, pp.C297~ (2018)
  22. Amici SA, "CD38 is robustly induced in human macrophages and monocytes in inflammatory conditions", Front Immunol, 9, pp.1593~ (2018)
  23. Polzonetti V, "Population variability in CD38activity : correlation with age and significant effect of TNF-α-308G>A and CD38 184C>G SNPs", Mol Genet Metab, 105, pp.502~507 (2012)
  24. Weiss R, "Nicotinamide : a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features", Innate Immun, 21, pp.813~826 (2015)
  25. Kong D, "Niacin promotes cardiac healing after myocardial infarction through activation of the myeloid prostaglandin D2 receptor subtype 1", J Pharmacol Exp Ther, 360, pp.435~444 (2017)
  26. Huynh PK, "Beneficial effects of nicotinamide on hypertensive mice with impaired endothelial nitric oxide function", J Exp Nephrol, 1, pp.1~8 (2020)
  27. Poyan Mehr A, "De novo NAD+ biosynthetic impairment in acute kidney injury in humans", Nat Med, 24, pp.1351~1359 (2018)
  28. Mateuszuk Ł, "Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside", Biochem Pharmacol, 178, pp.114019~ (2020)
  29. D’Onofrio N, "SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection", Antioxid Redox Signal, 28, pp.711~732 (2018)
  30. Gano LB, "The SIRT1 activator SRT1720reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice", Am J Physiol Heart Circ Physiol, 307, pp.H1754~H1763 (2014)
  31. Desdín-Micó G, "T cells with dysfunctional mitochondria induce multimorbidity and premature senescence", Science, 368, pp.1371~1376 (2020)
  32. de Picciotto NE, "Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice", Aging Cell, 15, pp.522~530 (2016)
  33. Hong G, "Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis", Free Radic Biol Med, 123, pp.125~137 (2018)
  34. Tarantini S, "Nicotinamide mononucleotide(NMN)supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice", Redox Biol, 24, pp.101192~ (2019)
  35. Kiss T, "Nicotinamide mononucleotide(NMN)supplementation promotes neurovascular rejuvenation in aged mice : transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and antiapoptotic effects", Geroscience, 42, pp.527~546 (2020)
  36. Csiszar A, "Resveratrol induces mitochondrial biogenesis in endothelial cells", Am J Physiol Heart Circ Physiol, 297, pp.H13~H20 (2009)
  37. Ungvari Z, "Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells", Am J Physiol Heart Circ Physiol, 297, pp.H1876~H1881 (2009)
  38. Ungvari Z, "Age-associated vascular oxidative stress, Nrf2 dysfunction, and NF-κB activation in the nonhuman primate Macaca mulatta", J Gerontol A Biol Sci Med Sci, 66, pp.866~875 (2011)
  39. Csiszár A, "Resveratrol encapsulated in novel fusogenic liposomes activates Nrf2 and attenuates oxidative stress in cerebromicrovascular endothelial cells from aged rats", J Gerontol A Biol Sci Med Sci, 70, pp.303~313 (2015)
  40. Pearson KJ, "Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span", Cell Metab, 8, pp.157~168 (2008)
  41. Martin AS, "Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model", JCI Insight, 2, pp.93885~ (2017)
  42. Dikalova AE, "Sirt3 impairment and SOD2 hyperacetylation in vascular oxidative stress and hypertension", Circ Res, 121, pp.564~574 (2017)
  43. Dikalova AE, "Mitochondrial deacetylase Sirt3 reduces vascular dysfunction and hypertension while sirt3 depletion in essential hypertension is linked to vascular inflammation and oxidative stress", Circ Res, 126, pp.439~452 (2020)
  44. Kiss T, "Nicotinamide mononucleotide(NMN)supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects", Geroscience, 41, pp.419~439 (2019)
  45. Escande C, "Flavonoid apigenin is an inhibitor of the NAD+ ase CD38 : implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome", Diabetes, 62, pp.1084~1093 (2013)
  46. Clayton ZS, "Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging", Am J Physiol Heart Circ Physiol, 321, pp.H185~H196 (2021)
  47. Kirkman DL, "Mitochondrial contributions to vascular endothelial dysfunction, arterial stiffness, and cardiovascular diseases", Am J Physiol Heart Circ Physiol, 320, pp.H2080~H2100 (2021)
  48. Abdellatif M, "Autophagy in cardiovascular health and disease", Prog Mol Biol Transl Sci, 172, pp.87~106 (2020)
  49. Ljubojević-Holzer S, "Loss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling", Cardiovasc Res, pp.cvab112~ (2021)
  50. LaRocca TJ, "Translational evidence that impaired autophagy contributes to arterial ageing", J Physiol, 590, pp.3305~3316 (2012)
  51. Abdellatif M, "Autophagy in cardiovascular aging", Circ Res, 123, pp.803~824 (2018)
  52. Michiels CF, "Defective autophagy in vascular smooth muscle cells alters contractility and Ca2+ homeostasis in mice", Am J Physiol Heart Circ Physiol, 308, pp.H557~H567 (2015)
  53. Wang Q, "Deletion of PRKAA triggers mitochondrial fission by inhibiting the autophagy-dependent degradation of DNM1L", Autophagy, 13, pp.404~422 (2017)
  54. Hsu CP, "Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes", Circ Res, 105, pp.481~491 (2009)
  55. Wang P, "Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia", Autophagy, 8, pp.77~87 (2012)
  56. Fan Y, "Endothelial TFEB(transcription factor EB)positively regulates postischemic angiogenesis", Circ Res, 122, pp.945~957 (2018)
  57. Zhang HN, "Sirtuins family as a target in endothelial cell dysfunction : implications for vascular ageing", Biogerontology, 21, pp.495~516 (2020)
  58. Lapierre LR, "Transcriptional and epigenetic regulation of autophagy in aging", Autophagy, 11, pp.867~880 (2015)
  59. Lee IH, "A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy", Proc Natl Acad Sci U S A, 105, pp.3374~3379 (2008)
  60. Huang R, "Deacetylation of nuclear LC3 drives autophagy initiation under starvation", Mol Cell, 57, pp.456~466 (2015)
  61. He J, "SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition", FEBS J, 284, pp.1324~1337 (2017)
  62. Fang EF, "Targeting on the NAD+-mitophagy axis to treat cardiovascular disease", Aging Med(Milton), 3, pp.151~152 (2020)
  63. Zimmermann A, "Targeting the mitochondriaproteostasis axis to delay aging", Front Cell Dev Biol, 9, pp.656201~ (2021)
  64. Sukoyan GV, "Effect of nadcin on energy supply system and apoptosis in ischemia-reperfusion injury to the myocardium", Bull Exp Biol Med, 146, pp.321~324 (2008)
  65. Sukoyan GV, "Effect of NAD on recovery of adenine nucleotide pool, phosphorylation potential, and stimulation of apoptosis during late period of reperfusion damage to myocardium", Bull Exp Biol Med, 139, pp.46~49 (2005)
  66. Liaudet L, "Myocardial ischemic preconditioning in rodents is dependent on poly(ADP-ribose)synthetase", Mol Med, 7, pp.406~417 (2001)
  67. Zhou L, "NAMPT", SIRT1 attenuate Ang II-induced vascular remodeling and vulnerability to hypertension by inhibiting the ROS, Oxid Med Cell Longev, pp.2020, 2020[DOI]
  68. Gorenne I, "Vascular smooth muscle cell sirtuin 1 protects against DNA damage and inhibits atherosclerosis", Circulation, 127, pp.386~396 (2013)
  69. Watson A, "Nicotinamide phosphoribosyltransferase in smooth muscle cells maintains genome integrity, resists aortic medial degeneration, and is suppressed in human thoracic aortic aneurysm disease", Circ Res, 120, pp.1889~1902 (2017)
  70. Mills KT, "Global disparities of hypertension prevalence and control : a systematic analysis of population-based studies from 90 countries", Circulation, 134, pp.441~450 (2016)
  71. Mills KT, "The global epidemiology of hypertension", Nat Rev Nephrol, 16, pp.223~237 (2020)
  72. Martens CR, "Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults", Nat Commun, 9, pp.1286~ (2018)
  73. Abdellatif M, "Nicotinamide for the treatment of heart failure with preserved ejection fraction", Sci Transl Med, 13, pp.eabd7064~ (2021)
  74. Li F, "Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia", Proc Natl Acad Sci U S A, 113, pp.13450~13455 (2016)
  75. Guse AH, "Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose(cADPR)", Curr Mol Med, 4, pp.239~248 (2004)
  76. Cho KH, "Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure", Am J Physiol Renal Physiol, 297, pp.F106~F113 (2009)
  77. Gan L, "CD38 deficiency alleviates Ang II-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice", Signal Transduct Target Ther, 6, pp.223~ (2021)
  78. Winnik S, "Protective effects of sirtuins in cardiovascular diseases : from bench to bedside", Eur Heart J, 36, pp.3404~3412 (2015)
  79. Méndez-Lara KA, "Nicotinamide prevents apolipoprotein B-containing lipoprotein oxidation, inflammation and atherosclerosis in apolipoprotein E-deficient mice", Antioxidants, 9, pp.E1162~ (2020)
  80. Domagala TB, "Nitric oxide production and endothelium-dependent vasorelaxation ameliorated by N1-methylnicotinamide in human blood vessels", Hypertension, 59, pp.825~832 (2012)
  81. Mateuszuk L, "Antiatherosclerotic effects of 1-methylnicotinamide in apolipoprotein E", low-density lipoprotein receptor-deficient mice : a comparison with nicotinic acid, 2016, pp.356, 514~524
  82. Jiang N, "N-methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E-deficient mice", Mol Nutr Food Res, 60, pp.1625~1636 (2016)
  83. Creider JC, "Niacin : another look at an underutilized lipid-lowering medication", Nat Rev Endocrinol, 8, pp.517~528 (2012)
  84. Romani M, "Niacin : an old lipid drug in a new NAD+ dress", J Lipid Res, 60, pp.741~746 (2019)
  85. HPS2-THRIVE Collaborative Group, "Effects of extended-release niacin with laropiprant in high-risk patients", N Engl J Med, 371, pp.203~212 (2014)
  86. AIM-HIGH Investigators, "Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy", N Engl J Med, 365, pp.2255~2267 (2011)
  87. Philpott AC, "Niacin improves lipid profile but not endothelial function in patients with coronary artery disease on high dose statin therapy", Atherosclerosis, 226, pp.453~458 (2013)
  88. Jenkins DJ, "Supplemental vitamins and minerals for CVD prevention and treatment", J Am Coll Cardiol, 71, pp.2570~2584 (2018)
  89. Jenkins DJ, "Supplemental vitamins and minerals for cardiovascular disease prevention and treatment : JACC focus seminar", J Am Coll Cardiol, 77, pp.423~436 (2021)
  90. Canner PL, "Fifteen year mortality in Coronary Drug Project patients : long-term benefit with niacin", J Am Coll Cardiol, 8, pp.1245~1255 (1986)
  91. Zeman M, "Niacin in the treatment of hyperlipidemias in light of new clinical trials : has niacin lost its place?", Med Sci Monit, 21, pp.2156~2162 (2015)
  92. D’Andrea E, "Assessment of the role of niacin in managing cardiovascular disease outcomes : a systematic review and meta-analysis", JAMA Netw Open, 2, pp.e192224~ (2019)
  93. Jiang Y, "Discovery of a novel niacin-lipoic acid dimer N2L attenuating atherosclerosis and dyslipidemia with non-flushing effects", Eur J Pharmacol, 868, pp.172871~ (2020)
  94. Garten A, "Physiological and pathophysiological roles of NAMPT and NAD metabolism", Nat Rev Endocrinol, 11, pp.535~546 (2015)
  95. Bermudez B, "Leukocyte overexpression of intracellular NAMPT attenuates atherosclerosis by regulating PPARγ-dependent monocyte differentiation and function", Arterioscler Thromb Vasc Biol, 37, pp.1157~1167 (2017)
  96. Nencioni A, "Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice", Thromb Haemost, 111, pp.308~322 (2014)
  97. Kong YY, "Nicotinamide phosphoribosyltransferase aggravates inflammation and promotes atherosclerosis in ApoE knockout mice", Acta Pharmacol Sin, 40, pp.1184~1192 (2019)
  98. Reyes LA, "Depletion of NADP(H)due to CD38 activation triggers endothelial dysfunction in the postischemic heart", Proc Natl Acad Sci U S A, 112, pp.11648~11653 (2015)
  99. Boslett J, "Luteolinidin protects the postischemic heart through CD38 inhibition with preservation of NAD(P)(H)", J Pharmacol Exp Ther, 361, pp.99~108 (2017)
  100. Boslett J, "Genetic deletion of CD38 confers post-ischemic myocardial protection through preserved pyridine nucleotides", J Mol Cell Cardiol, 118, pp.81~94 (2018)
  101. Boslett J, "Inhibition of CD38 with the thiazoloquin(az)olin(on)e 78c protects the heart against postischemic injury", J Pharmacol Exp Ther, 369, pp.55~64 (2019)
  102. Liu L, "Exogenous nicotinamide adenine dinucleotide administration alleviates ischemia", reperfusion-induced oxidative injury in isolated rat hearts via Sirt5-SDH-succinate pathway, 2019, pp.858, 172520~
  103. Zhai X, "Exogenous supplemental NAD+ protect myocardium against myocardial ischemic", reperfusion injury in swine model, 2019, pp.11, 6066~6074
  104. Sukhodub A, "Nicotinamide-rich diet protects the heart against ischaemiareperfusion in mice : a crucial role for cardiac SUR2A", Pharmacol Res, 61, pp.564~570 (2010)
  105. Nie H, "Oral delivery of carrier-free dual-drug nanocrystal selfassembled microspheres improved NAD+ bioavailability and attenuated cardiac ischemia", reperfusion injury in mice, 2021, pp.28, 433~444
  106. Hosseini L, "Melatonin and nicotinamide mononucleotide attenuate myocardial ischemia", reperfusion injury via modulation of mitochondrial function and hemodynamic parameters in aged rats, 2020, pp.25, 240~250
  107. Yamamoto T, "Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion", PLoS One, 9, pp.e98972~ (2014)
  108. Abdellatif M, "Autophagy promotes longevity-except in the presence of ‘leaky’ mitochondria", Cardiovasc Res, 115, pp.e118~e120 (2019)
  109. Digby JE, "Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms", Arterioscler Thromb Vasc Biol, 32, pp.669~676 (2012)
  110. Wu BJ, "Niacin inhibits vascular inflammation via the induction of heme oxygenase-1", Circulation, 125, pp.150~158 (2012)
  111. van der Hoorn JW, "Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden. CETP mice", Arterioscler Thromb Vasc Biol, 28, pp.2016~2022 (2008)
  112. Horimatsu T, "Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms : role of NAD+", nicotinamide, 2020, pp.116, 2226~2238
  113. Bogan KL, "Nicotinic acid, nicotinamide, and nicotinamide riboside : a molecular evaluation of NAD+ precursor vitamins in human nutrition", Annu Rev Nutr, 28, pp.115~130 (2008)
  114. Oller J, "Extracellular tuning of mitochondrial respiration leads to aortic aneurysm", Circulation, 143, pp.2091~2109 (2021)
  115. Grunewald M, "Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span", Science, 373, pp.eabc8479~ (2021)
  116. Chen J, "High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging", Sci Adv, 7, pp.eabd7819~ (2021)
  117. Donato AJ, "Mechanisms of dysfunction in the aging vasculature and role in age-related disease", Circ Res, 123, pp.825~848 (2018)
  118. Shabir O, "Neurovascular dysfunction in vascular dementia, Alzheimer’s and atherosclerosis", BMC Neurosci, 19, pp.62~ (2018)
  119. Traba J, "Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects", J Clin Invest, 125, pp.4592~4600 (2015)
  120. Elhassan YS, "Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and antiinflammatory signatures", Cell Reports, 28, pp.1717~1728 (2019)
  121. Knip M, "Safety of high-dose nicotinamide : a review", Diabetologia, 43, pp.1337~1345 (2000)
  122. Yoshino M, "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women", Science, 372, pp.1224~1229 (2021)
  123. Irie J, "Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men", Endocr J, 67, pp.153~160 (2020)
  124. Dower JI, "Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health : a randomized, double-blind, placebo-controlled, crossover trial", Am J Clin Nutr, 101, pp.914~921 (2015)
  125. Pfeuffer M, "Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms", Nutr Metab Cardiovasc Dis, 23, pp.403~409 (2013)
  126. Abdellatif M, "NAD+ metabolism and cardiometabolic health : the human evidence", Cardiovasc Res, 117, pp.e106~e109 (2021)
  127. Liu L, "Quantitative analysis of NAD synthesis-breakdown fluxes", Cell Metab, 27, pp.1067~1080 (2018)
  128. Nakahata Y, "Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1", Science, 324, pp.654~657 (2009)
  129. Winter SL, "Hepatic toxicity from large doses of vitamin B3(nicotinamide)", N Engl J Med, 289, pp.1180~1182 (1973)
  130. Diguet N, "Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy", Circulation, 137, pp.2256~2273 (2018)
  131. Tong D, "NAD+ repletion reverses heart failure with preserved ejection fraction", Circ Res, 128, pp.1629~1641 (2021)
  132. Kühnast S, "Niacin reduces atherosclerosis development in APOE*3Leiden. CETP mice mainly by reducing nonHDLcholesterol", PLoS One, 8, pp.e66467~ (2013)
  133. Tong DL, "Nicotinamide pretreatment protects cardiomyocytes against hypoxia-induced cell death by improving mitochondrial stress", Pharmacology, 90, pp.11~18 (2012)

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