title: Nicotinamide adenine dinucleotide homeostasis and signalling in heart disease: Pathophysiological implications and therapeutic potential.
abstract: Heart failure is a highly morbid syndrome generating enormous socio-economic costs. The failing heart is characterized by a state of deficient bioenergetics that is not currently addressed by classical clinical approaches. Nicotinamide adenine dinucleotide (NAD(+)/NADH) is a major coenzyme for oxidoreduction reactions in energy metabolism; it has recently emerged as a signalling molecule with a broad range of activities, ranging from calcium (Ca(2+)) signalling (CD38 ectoenzyme) to the epigenetic regulation of gene expression involved in the oxidative stress response, catabolic metabolism and mitochondrial biogenesis (sirtuins, poly[adenosine diphosphate-ribose] polymerases [PARPs]). Here, we review current knowledge regarding alterations to myocardial NAD homeostasis that have been observed in various models of heart failure, and their effect on mitochondrial functions, Ca(2+), sirtuin and PARP signalling. We highlight the therapeutic approaches that are currently in use or in development, which inhibit or stimulate NAD(+)-consuming enzymes, and emerging approaches aimed at stimulating NAD biosynthesis in the failing heart.
authors.affiliation: CNRS UMR8256-Inserm U1164, Biology of Adaptation and Ageing, Institute of Biology Paris-Seine, University Pierre-and-Marie-Curie Paris 6, 7, quai Saint-Bernard, 75005 Paris, France. Electronic address: mathias.mericskay@inserm.fr.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mericskay
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002317:Cardiovascular Agents / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D044127:Epigenesis, Genetic; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D037761:Sirtuins / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D037761:Sirtuins
keywords: CD38; Energy metabolism; Heart failure; Insuffisance cardiaque; Métabolisme énergétique; Nicotinamide adenine dinucleotide; Nicotinamide adénine dinucléotide; PARP; Sirtuin; Sirtuine