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Cardiac NAD+ depletion in mice promotes hypertrophic cardiomyopathy and arrhythmias prior to impaired bioenergetics.
Doan, Khanh V; Luongo, Timothy S; Ts'olo, Thato T; Lee, Won Dong; Frederick, David W; Mukherjee, Sarmistha; Adzika, Gabriel K; Perry, Caroline E; Gaspar, Ryan B; Walker, Nicole; Blair, Megan C; Bye, Nicole; Davis, James G; Holman, Corey D; Chu, Qingwei; Wang, Lin; Rabinowitz, Joshua D; Kelly, Daniel P; Cappola, Thomas P; Margulies, Kenneth B; Baur, Joseph A.
Afiliación
  • Doan KV; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Luongo TS; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ts'olo TT; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Lee WD; Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
  • Frederick DW; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Mukherjee S; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Adzika GK; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Perry CE; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Gaspar RB; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Walker N; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Blair MC; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Bye N; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Davis JG; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Holman CD; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Chu Q; Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Wang L; Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
  • Rabinowitz JD; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Kelly DP; Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
  • Cappola TP; Department of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Margulies KB; Department of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Baur JA; Department of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nat Cardiovasc Res ; 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39294272
ABSTRACT
Nicotinamide adenine dinucleotide (NAD+) is an essential co-factor in metabolic reactions and co-substrate for signaling enzymes. Failing human hearts display decreased expression of the major NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) and lower NAD+ levels, and supplementation with NAD+ precursors is protective in preclinical models. Here we show that Nampt loss in adult cardiomyocytes caused depletion of NAD+ along with marked metabolic derangements, hypertrophic remodeling and sudden cardiac deaths, despite unchanged ejection fraction, endurance and mitochondrial respiratory capacity. These effects were directly attributable to NAD+ loss as all were ameliorated by restoring cardiac NAD+ levels with the NAD+ precursor nicotinamide riboside (NR). Electrocardiograms revealed that loss of myocardial Nampt caused a shortening of QT intervals with spontaneous lethal arrhythmias causing sudden cardiac death. Thus, changes in NAD+ concentration can have a profound influence on cardiac physiology even at levels sufficient to maintain energetics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nat Cardiovasc Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nat Cardiovasc Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido