Cigarette Smoke Exposure and Hypercholesterolemia Increase Mitochondrial Damage in Cardiovascular Tissues

Abstract

Background-A shared feature among cardiovascular disease risk factors is increased oxidative stress. Because mitochondria are susceptible to damage mediated by oxidative stress, we hypothesized that risk factors (secondhand smoke and hypercholesterolemia) are associated with increased mitochondrial damage in cardiovascular tissues. Methods and Results-Atherosclerotic lesion formation, mitochondrial DNA damage, protein nitration, and specific activities of mitochondrial proteins in cardiovascular tissues from age-matched C57 and apoE Ϫ/Ϫ mice exposed to filtered air or secondhand smoke were quantified. Both secondhand smoke and hypercholesterolemia were associated with significantly increased mitochondrial DNA damage and protein nitration. Tobacco smoke exposure also resulted in significantly decreased specific activities of mitochondrial enzymes. The combination of secondhand smoke and hypercholesterolemia resulted in increased atherosclerotic lesion formation and even greater levels of mitochondrial damage. Conclusions-These

Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway

“…Methods for aorta preparation and en face morphometry to quantitate lesions were modified from established techniques (22). Aortas were fixed, cleaned, stained with oil red O (Sigma) to visualize intimal fatty lesions from the proximal arch to the iliac bifurcation, and flattened onto slides (9).…”

Mitochondrial DNA Content Increase in Response to Cigarette Smoking

“…Other small studies have provided conflicting evidence for and against mtDNA injury related to tobacco exposure in human cohorts (23,24). Tobacco smoke itself is a complex mixture of thousands of compounds with varied biological effects, but studies that have examined the effect of tobacco smoke as a whole have shown that tobacco smoke induces mitochondrial damage and depolarization, as well as mtDNA damage (25), and that this effect can be blocked by treatment with antioxidants (26,27). Increases in mtDNA content and declines in mitochondrial function are associated with aging and are observed in response to DNA-damaging agents, including tobacco smoke.…”

Mitochondria-Targeted Antioxidant MitoQ 10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy

“…4 Extensive evidence suggests that mitochondrial DNA damage occurs in cardiovascular disease in humans, animal models, and cellular models. 3,[7][8][9] Mitochondria are normally protected from oxidative damage by a multilayer network of mitochondrial antioxidant systems. 10,11 These include the mitochondrial matrix enzyme manganese superoxide dismutase, which converts the O 2 Ϫ anion to hydrogen peroxide, glutathione peroxidase, and peroxiredoxins 3 and 5, which readily convert hydrogen peroxide to water 7,10 and ultimately prevent forms of mitochondrial oxidative damage, eg, lipid peroxidation.…”