Nicotinamide Riboside Restores NAD+ Levels and Improves Heart Function in Cardiomyopathy: Preclinical Findings

Synopsis

Cardiomyopathy caused by mutations in the lamin A/C gene (LMNA cardiomyopathy) leads to heart muscle and electrical dysfunction, often resulting in heart failure. Currently, there is no targeted therapy that addresses the underlying molecular causes of this condition. Recent research suggests that the level of cellular nicotinamide adenine dinucleotide (NAD+) is crucial for heart function. NAD+ is mainly produced through salvage pathways from vitamin B3. This study found that the NAD+ salvage pathway is disrupted in the hearts of mice and humans with LMNA mutations, affecting the activity of PARP-1, an important NAD-dependent enzyme. Oral treatment with nicotinamide riboside, a natural vitamin B3 precursor of NAD+, significantly increased NAD+ levels, enhanced PARP-1 activity, and improved the structure and function of the left ventricle in a mouse model of LMNA cardiomyopathy. These findings offer new insights into the mechanisms and potential treatments for LMNA-related dilated cardiomyopathy.

Journal

Human Molecular Genetics