Nicotinamide Riboside Restores Vascular Health in ACTA2 Mutation: Preclinical Findings

Synopsis

Mutations in ACTA2 affecting arginine 179 cause early-onset strokes due to moyamoya-like artery blockages. This study found that mutant smooth muscle cells (SMCs) remain immature, highly migratory, and rely on glycolysis instead of normal mitochondrial metabolism. Treatment with nicotinamide riboside (NR) boosted mitochondrial respiration, promoted SMC differentiation, and reduced cell migration. In mice with the Acta2R179C mutation, arterial injury led to fatal vessel occlusions and brain damage, while NR treatment prevented vascular blockage, neurological symptoms, and neuron loss. These findings show that NR corrects SMC metabolic dysfunction and prevents moyamoya-like vascular disease linked to ACTA2 mutations.

Journal

Nature Communications