Format

Send to

Choose Destination
Hum Mol Genet. 2018 Nov 15;27(22):3870-3880. doi: 10.1093/hmg/ddy278.

Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation.

Author information

1
Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, Institut de Myologie, Paris, France.
2
INSERM UMR-S 1180 - LabEx LERMIT - DHU TORINO, Institut Paris-Saclay d'Innovation Therapeutique (IPSIT-US31-UMS3679), Faculty of Pharmacy, Univ Paris-Sud, Université Paris-Saclay, Chatenay-Malabry, France.
3
Sorbonne Université, UPMC Paris 06, INSERM UMS28 Phénotypage du petit animal, Faculté de Médecine Pierre et Marie Curie, Paris, France.
4
Cardiology Department, Cochin Hospital, Filière Neuromusculaire, Paris-Descartes University, Sorbonne Paris Cité University, Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscle and electrical dysfunction of the heart, often leading to heart failure-related disability. There is currently no specific therapy available for patients that target the molecular pathophysiology of LMNA cardiomyopathy. Recent studies suggested that nicotinamide adenine dinucleotide (NAD+) cellular content could be a critical determinant for heart function. Biosynthesis of NAD+ from vitamin B3 (known as salvage pathways) is the primary source of NAD+. We showed here that NAD+ salvage pathway was altered in the heart of mouse and human carrying LMNA mutation, leading to an alteration of one of NAD+ co-substrate enzymes, PARP-1. Oral administration of nicotinamide riboside, a natural NAD+ precursor and a pyridine-nucleoside form of vitamin B3, leads to a marked improvement of the NAD+ cellular content, an increase of PARylation of cardiac proteins and an improvement of left ventricular structure and function in a model of LMNA cardiomyopathy. Collectively, our results provide mechanistic and therapeutic insights into dilated cardiomyopathy caused by LMNA mutations.

PMID:
30053027
DOI:
10.1093/hmg/ddy278
Free full text

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for HAL archives ouvertes
Loading ...
Support Center