Nicotinamide Riboside Reverses Pulmonary Hypertension: Preclinical Findings

Synopsis

Pulmonary hypertension (PH) is a deadly lung vascular disease caused by endothelial dysfunction and vascular remodeling that strain the heart. This study identified Sirtuin 7 (SIRT7)—a NAD+-dependent enzyme—as a critical regulator of pulmonary artery endothelial cell (PAEC) health. Researchers found that SIRT7 levels were significantly decreased in lung tissues and endothelial cells from both PH patients and mouse models of PH. Loss of SIRT7 worsened the disease, increasing blood pressure in the right ventricle and heart enlargement. Mechanistically, SIRT7 maintains endothelial stability by deacetylating Krüppel-like factor 4 (KLF4), a transcription factor essential for vascular function. Without SIRT7, KLF4 becomes unstable and degraded, leading to endothelial cell damage and abnormal vessel growth. Treatment with nicotinamide riboside (NR), a vitamin B3–derived NAD+ precursor, restored NAD+ levels, reactivated SIRT7, stabilized KLF4, and reversed vascular remodeling and heart strain in PH mice. These findings reveal that boosting NAD+ with NR or targeting the SIRT7/KLF4 pathway offers a promising new therapeutic strategy for treating pulmonary hypertension.

Journal

Cardiovascular Research