Sirtuin-1 directly binds and deacetylates hepatic PCSK9 thereby promoting the inhibition of LDL receptor degradation.

ABSTRACT:

Aims

Low-density lipoprotein (LDL)-cholesterol is causally involved in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Pharmacological activation of the intracellular NAD + -dependent deacetylase Sirtuin-1 (SIRT1) reduces plasma LDL-cholesterol levels by increasing hepatic LDL-receptor (LDLR) expression, which intriguingly associates with atheroprotective effects. Recent studies have identified the presence of SIRT1 in plasma, however, its effects remain elusive. We found that plasma levels of SIRT1 to be decreased in atherosclerotic mice compared with wild-type controls and aimed to investigate the therapeutic potential of systemic SIRT1 restoration on lipid metabolism and plaque burden in atherosclerotic mice and dissect the underlying molecular mechanisms involved.<

SUBMITTER: Velagapudi S 

PROVIDER: S-EPMC12352300 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature