Raising NAD+ via Nicotinamide Riboside Enhances Heart Function in Heart Failure: Preclinical Findings

Synopsis

Boosting cellular NAD⁺ levels has been shown to prevent heart problems in various models of heart failure, but how it works at the molecular level is not fully understood. Most studies focused on preventive treatments and mechanisms involving Sirt3 and mitochondrial protein regulation. This study tested nicotinamide riboside chloride (NR) in mice with established heart failure caused by pressure overload, including both wild-type and SIRT3-deficient mice. NR improved mitochondrial function and slowed heart failure progression in both types of mice. The therapy worked by enhancing NAD(H)-sensitive SDR proteins, such as Mrpp2, which supports mitochondrial RNA processing and energy production, and by activating RXRα/PPARα signaling to restore mitochondrial metabolism. Similar defects in Mrpp2 were observed in human failing hearts, suggesting a shared mechanism. These findings highlight SDR proteins as key regulators of mitochondrial function and show that NAD-based therapies can benefit even pre-existing heart failure, independent of Sirt3 activity.

Journal

Circulation