NAD Metabolism Regulates Proliferation of Macrophages in Atherosclerosis.

ABSTRACT:

Background

In genetic studies with the Hybrid Mouse Diversity Panel, we previously identified a chromosome 9 locus for atherosclerosis. We now identify NNMT (nicotinamide N-methyltransferase), an enzyme that degrades nicotinamide, as the causal gene in the locus and show that the underlying mechanism involves salvage of nicotinamide to nicotinamide adenine dinucleotide (NAD).

Methods

Gain/loss of function studies in macrophages were performed to examine the role of NAD levels in macrophage proliferation and apoptosis in atherosclerosis.

Results

Global inhibition of NNMT using an antisense oligonucleotide reduced atherosclerosis lesion area 5- to 10-fold in both male and female mice on a hyperlipidemic background. Selective inhibition of NNMT in liver and adipos

SUBMITTER: Sinha SK 

PROVIDER: S-EPMC12614180 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature