Cigarette Smoke and High Cholesterol Increase Mitochondrial Damage in Cardiovascular Tissues

Scott Ballinger, Ph.D.
University of Texas Medical Branch
ES11172 and ES09318

Background: A growing body of scientific evidence indicates that atherosclerotic lesions, the plaques that lead to hardening of the arteries and cardiac artery blockages, result from oxidative stress caused by metabolic defects and environmental exposures. Exposure to secondhand smoke (SHS) is considered a risk factor for heart disease and it has been linked to decreased blood-levels of antioxidants such as vitamins E and C, increased lipid peroxidation, and increased rates of plaque formation.

The generation of reactive oxygen and nitrogen species causes mitochondrial injury ranging from mitochondrial DNA (mtDNA) damage, decreased adenine nucleotide translocator (ANT) activity, to changes in mitochondrial proteins. While the mtDNA encodes genes necessary for oxidative phosphorylation, the ANT enzyme moves adenine nucleotides across the inner mitochondrial membrane, and thus, both processes are essential for energy production by the mitochondrion, its principal job in the cell. Therefore, oxidative stress may cause mitochondrial damage that could impact a variety of cellular functions including energy production and cell signaling.

Advance: These investigators used a mouse model of SHS exposure and a transgenic mouse model of high cholesterol to determine whether SHS and high cholesterol can cause mitochondrial damage in cardiovascular tissues. The results show that both SHS and elevated cholesterol were associated with significantly increased mtDNA damage and protein nitration. Tobacco smoke exposure also caused decreased activities of certain mitochondrial enzymes. SHS and high cholesterol together resulted in increased plaque formation and even greater levels of mitochondrial damage.

Implication: The finding reported by these investigators coincide with present theories that oxidative stress mediates cardiovascular disease by causing mitochondrial damage and dysfunction. These changes ultimately lead to decreased cellular energy production and cellular dysfunction which are important early events in cardiovascular disease.

Citation: Knight-Lozano CA, Young CG, Burow DL, Hu ZY, Uyeminami D, Pinkerton KE, Ischiropoulos H, Ballinger SW. Cigarette smoke exposure and hypercholesterolemia increase mitochondrial damage in cardiovascular tissues. Circulation. 2002 Feb 19;105(7):849-54.