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(Circulation. 2002;105:849.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Cigarette Smoke Exposure and Hypercholesterolemia Increase Mitochondrial Damage in Cardiovascular Tissues

Cynthia A. Knight-Lozano, BS; Christal G. Young, BS; David L. Burow, MS; Zhao Yong Hu, MD; Dale Uyeminami, BS; Kent E. Pinkerton, PhD; Harry Ischiropoulos, PhD; Scott W. Ballinger, PhD

From the Division of Cardiology (C.A.K., C.Y.G., D.L.B., Z.H., S.W.B.), University of Texas Medical Branch, Galveston, Tex; Institute of Toxicology and Environmental Health (D.U., K.E.P.), University of California, Davis; and Children’s Hospital of Philadelphia (H.I.), Abramson Pediatric Research Center, Philadelphia, Pa.

Correspondence to S.W. Ballinger, PhD, Department of Internal Medicine, Division of Cardiology, University of Texas Medical Branch, Galveston, TX 77555-1064. E-mail swballin{at}utmb.edu

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^-/- 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.

Key Words: atherosclerosis • smoking • hypercholesterolemia • mitochondria

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