Mitochondrial DNA Damage, Oxidative Stress, And Atherosclerosis

The study explored the role of mitochondrial DNA (mtDNA) damage in atherosclerosis, revealing that mtDNA damage exacerbated plaque development independently of reactive oxygen species (ROS). Using ApoE-deficient mice and transgenic mice with defective mitochondrial DNA polymerase, researchers found that mtDNA lesions preceded plaque formation and correlated with decreased mitochondrial respiratory activity. Despite increased mtDNA damage, ROS production did not rise, suggesting other mechanisms, such as decreased ATP levels and increased apoptosis, were at play. Human data from the VIVA trial supported these findings, linking mtDNA damage to higher-risk plaques. The study suggested that targeting mitochondrial health, rather than antioxidants, might be a more effective therapeutic approach.