Cigarette smoke exposure and hypercholesterolemia increase mitochondrial damage in cardiovascular tissues.
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.


RESULTS
Atherosclerotic lesion formation, mitochondrial DNA damage, protein nitration, and specific activities of mitochondrial proteins in cardiovascular tissues from age-matched C57 and apoE(-/-) 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 data are consistent with the hypothesis that cardiovascular disease risk factors cause mitochondrial damage and dysfunction.
Knight-Lozano
Cynthia A
CA
Division of Cardiology, University of Texas Medical Branch, Galveston, Tex 77555-1064, USA.
Young
Christal G
CG
Burow
David L
DL
Hu
Zhao Yong
ZY
Uyeminami
Dale
D
Pinkerton
Kent E
KE
Ischiropoulos
Harry
H
Ballinger
Scott W
SW
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology*; D002319:Cardiovascular System / Q000473:pathology*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism; D018450:Disease Progression; D006937:Hypercholesterolemia / Q000150:complications* / Q000235:genetics; D019570:Inhalation Exposure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D004272:DNA, Mitochondrial; D000226:Mitochondrial ADP, ATP Translocases; D013482:Superoxide Dismutase; D014028:Tobacco Smoke Pollution; D014443:Tyrosine; D000099156:Superoxide Dismutase 2; C002744:3-nitrotyrosine