Acetaldehyde Dehydrogenase 2 regulates HMG-CoA reductase stability and cholesterol synthesis in the liver.

ABSTRACT: HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol biosynthesis and the target for cholesterol-lowering therapy. Acetaldehyde dehydrogenase 2 (ALDH2) is primarily responsible for detoxifying ethanol-derived acetaldehyde and endogenous lipid aldehydes derived from lipid peroxidation. Epidemiological and Genome Wide Association Studies (GWAS) have linked an inactive ALDH2 rs671 variant, responsible for alcohol flush in nearly 8% world population and 40% of Asians, with cholesterol levels and higher risk of cardiovascular disease (CVD) but the underlying mechanism remains elusive. Here we find that the cholesterol levels in the serum and liver of ALDH2 knockout (AKO) and ALDH2 rs671 knock-in (AKI) mice are significantly increased, consistent with the increase of intermediate

SUBMITTER: Zhong S 

PROVIDER: S-EPMC7995661 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature