TY - JOUR
TI - Role of endothelial NAD+ deficiency in age-related vascular dysfunction
Y1 - 2019///
ID - publicatio18568
AV - public
JF - AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY
N2 - Age-related alterations in endothelium and the resulting vascular dysfunction critically contribute to a range of pathological conditions associated with old age. To rationally develop therapies that improve vascular health and thereby increase health span and lifespan in older adults, it will be essential to understand the cellular and molecular mechanisms contributing to vascular aging. Pre-clinical studies in model organisms demonstrate that NAD+ availability decreases with age in multiple tissues and that supplemental NAD+ precursors can ameliorate many age-related cellular impairments. Here we provide a comprehensive overview of NAD+ dependent pathways (including the NAD+ utilizing sirtuins and poly (ADP-ribose) polymerase enzymes) and the potential consequences of endothelial NAD+ deficiency in vascular aging. The multifaceted vasoprotective effects of treatments that reverse the age-related decline in cellular NAD+ levels are discussed. The preventive and therapeutic potential of NAD+ intermediates as effective, clinically relevant interventions in older adults at risk for ischemic heart disease, vascular cognitive impairment and other common geriatric conditions and diseases that involve vascular pathologies (e.g. sarcopenia, frailty) is critically discussed. We propose that NAD+ precursors (e.g., nicotinamide riboside, nicotinamide mononucleotide, niacin) should be considered as a critical component of combination therapies to slow the vascular aging process and increase cardiovascular health span.
SN - 0363-6135
VL - 316
UR - http://doi.org/10.1152/ajpheart.00039.2019
SP - H1253
N1 - Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, Oklahoma City, OK 73104, United States
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary
Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Pulmonology, Semmelweis University, Budapest, Hungary
Department of Health Promotion Sciences, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Cited By :1
Export Date: 23 August 2019
CODEN: AJPPD
Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, United States; email: zoltan-ungvari@ouhsc.edu
Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, Oklahoma City, OK 73104, United States
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary
Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Pulmonology, Semmelweis University, Budapest, Hungary
Department of Health Promotion Sciences, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Cited By :2
Export Date: 31 August 2019
CODEN: AJPPD
Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, United States; email: zoltan-ungvari@ouhsc.edu
Chemicals/CAS: nicotinamide adenine dinucleotide, 53-84-9; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, 58319-92-9; reduced nicotinamide adenine dinucleotide phosphate, 53-57-6
Funding details: Presbyterian Health Foundation
Funding details: National Institute on Aging, R01-AG047879, R01-AG038747, R01-AG055395, R01-AG043483
Funding details: Alice Kleberg Reynolds Foundation
Funding details: EFOP-3.6.1-16-2016-00008
Funding details: National Institute of Diabetes and Digestive and Kidney Diseases, R01-DK098656
Funding details: National Heart, Lung, and Blood Institute, R01HL132553
Funding details: 3P30AG050911-02S1
Funding details: Oklahoma Center for the Advancement of Science and Technology
Funding details: American Heart Association
Funding details: T32AG052363
Funding details: National Institute of General Medical Sciences, U54GM104938
Funding details: National Institute of Neurological Disorders and Stroke, R01-NS056218, R01-NS100782
Funding text 1: This work was supported by grants from the American Heart Association (to S. Tarantini), National Institute on Aging (NIA; R01-AG055395 to Z. Ungvari, R01-AG047879 and R01-AG038747 to A. Csiszar, and R01-AG043483 to J. A. Baur), National Heart, Lung, and Blood Institute (R01HL132553), National Institute of Neurological Disorders and Stroke (R01-NS056218 to A. Csiszar and R01-NS100782 to Z. Ungvari), National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK098656 to J. A. Baur), NIA-supported Geroscience Training Program in Oklahoma (T32AG052363), NIA-supported Oklahoma Nathan Shock Center (3P30AG050911-02S1 to Z. Ungvari and A. Csiszar), U.S. National Institutes of Health-supported Oklahoma Shared Clinical and Translational Resources (to A. Yabluchanskiy), National Institute of General Medical Sciences (U54GM104938), Oklahoma Center for the Advancement of Science and Technology (to A. Csiszar, Z. Ungvari, and A. Yabluchans-kiy), Presbyterian Health Foundation (to Z. Ungvari, A. Csiszar, and A. Yabluchanskiy), European Union-funded Hungarian grant (EFOP-3.6.1-16-2016-00008), and Reynolds Foundation (to Z. Ungvari and A. Csiszar).
Funding Agency and Grant Number: American Heart AssociationAmerican Heart Association; National Institute on Aging (NIA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01-AG055395, R01-AG047879, R01-AG038747, R01-AG043483]; National Heart, Lung, and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL132553]; National Institute of Neurological Disorders and StrokeUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01-NS056218, R01-NS100782]; National Institute of Diabetes and Digestive and Kidney DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01-DK098656]; NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [T32AG052363, 3P30AG050911-02S1]; U.S. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; National Institute of General Medical SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [U54GM104938]; Oklahoma Center for the Advancement of Science and Technology; Presbyterian Health Foundation; European UnionEuropean Union (EU) [EFOP-3.6.1-16-2016-00008]; Reynolds Foundation
Funding text: This work was supported by grants from the American Heart Association (to S. Tarantini), National Institute on Aging (NIA; R01-AG055395 to Z. Ungvari, R01-AG047879 and R01-AG038747 to A. Csiszar, and R01-AG043483 to J. A. Baur), National Heart, Lung, and Blood Institute (R01HL132553), National Institute of Neurological Disorders and Stroke (R01-NS056218 to A. Csiszar and R01-NS100782 to Z. Ungvari), National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK098656 to J. A. Baur), NIA-supported Geroscience Training Program in Oklahoma (T32AG052363), NIA-supported Oklahoma Nathan Shock Center (3P30AG050911-02S1 to Z. Ungvari and A. Csiszar), U.S. National Institutes of Health-supported Oklahoma Shared Clinical and Translational Resources (to A. Yabluchanskiy), National Institute of General Medical Sciences (U54GM104938), Oklahoma Center for the Advancement of Science and Technology (to A. Csiszar, Z. Ungvari, and A. Yabluchanskiy), Presbyterian Health Foundation (to Z. Ungvari, A. Csiszar, and A. Yabluchanskiy), European Union-funded Hungarian grant (EFOP-3.6.1-16-2016-00008), and Reynolds Foundation (to Z. Ungvari and A. Csiszar).
Cited By :6
Export Date: 11 November 2019
CODEN: AJPPD
Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, United States; email: zoltan-ungvari@ouhsc.edu
Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, Oklahoma City, OK 73104, United States
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary
Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Pulmonology, Semmelweis University, Budapest, Hungary
Department of Health Promotion Sciences, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Cited By :9
Export Date: 2 December 2019
CODEN: AJPPD
Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, United States; email: zoltan-ungvari@ouhsc.edu
Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, Oklahoma City, OK 73104, United States
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary
Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Pulmonology, Semmelweis University, Budapest, Hungary
Department of Health Promotion Sciences, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Cited By :10
Export Date: 13 January 2020
CODEN: AJPPD
Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, United States; email: zoltan-ungvari@ouhsc.edu
Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, Oklahoma City, OK 73104, United States
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary
Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Pulmonology, Semmelweis University, Budapest, Hungary
Department of Health Promotion Sciences, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Cited By :12
Export Date: 24 March 2020
CODEN: AJPPD
Correspondence Address: Ungvari, Z.; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1311, United States; email: zoltan-ungvari@ouhsc.edu
Chemicals/CAS: nicotinamide adenine dinucleotide, 53-84-9; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, 58319-92-9; reduced nicotinamide adenine dinucleotide phosphate, 53-57-6
IS - 6
A1 - Csiszar Anna
A1 - Tarantini Stefano
A1 - Yabluchanskiy Andrij
A1 - Balasubramanian Priya
A1 - Kiss Tamás
A1 - Farkas Eszter
A1 - Baur Joseph A.
A1 - Ungvári Zoltán István
EP - H1266
ER -