DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome.

ABSTRACT:

Rationale

DNA damage is present in both genomic and mitochondrial DNA in atherosclerosis. However, whether DNA damage itself promotes atherosclerosis, or is simply a byproduct of the risk factors that promote atherosclerosis, is unknown.

Objective

To examine the effect of DNA damage on atherosclerosis, we studied apolipoprotein (Apo)E(-/-) mice that were haploinsufficient for the protein kinase ATM (ataxia telangiectasia mutated), which coordinates DNA repair.

Methods and results

ATM(+/-)/ApoE(-/-) mice developed accelerated atherosclerosis and multiple features of the metabolic syndrome, including hypertension, hypercholesterolemia, obesity, steatohepatitis, and glucose intolerance. Transplantation with ATM(+/+) bone marrow attenuated atherosclerosis but not the meta

SUBMITTER: Mercer JR 

PROVIDER: S-EPMC2982998 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature