© 2000 American Heart Association, Inc.
Editorials |
Canaries in the Coal Mine
Mitochondrial DNA and Vascular Injury From Reactive Oxygen Species
From the Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to R. Sanders Williams, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NB11.200, Dallas, TX 75390-8573. E-mail williams@ryburn.swmed.edu
Key Words: atherosclerosis • mitochondria • reactive oxygen species
 |
Introduction |
|---|
Mitochondrial DNA (mtDNA), that curious and ancient genomic relic from the birth of the first eukaryotes, has surfaced once again in a context pertinent to cardiovascular biology and disease. In this issue of Circulation Research, Ballinger et al1 describe how human vascular endothelial and smooth muscle cells accumulate lesions in mtDNA when exposed to superoxide, hydrogen peroxide, nitric oxide, or peroxynitrite. In response to conditions that generate reactive oxygen species, damage to mtDNA is much more marked than damage to nuclear DNA, at least as assessed at a single transcriptionally inactive nuclear gene (ß-globin). Ballinger et al also describe concomitant decreases in steady-state concentrations of mRNA transcribed from mitochondrial genes, in mitochondrial protein synthesis and membrane potential, and in total cellular ATP pools. They propose that these effects of reactive oxygen species contribute to vascular cell dysfunction so as to promote or accelerate the development of atherosclerosis.
The findings of Ballinger et al1 are reminiscent of
previous observations in which increased frequency of mtDNA mutations
was implicated in the pathobiology of cardiovascular
disease. Mutated forms of mtDNA increase in number as a function of
increasing age or ischemic heart disease in the human
myocardium.2 3 Numerous reports describe mtDNA
mutations in humans or animals with hypertrophic or dilated
cardiomyopathy,4 5 6 and a similarly
increased burden of mutated forms of mtDNA has been described in neural
tissues of humans with neurodegenerative diseases.7 8 9
Although few studies have directly examined the mechanisms by which
mtDNA damage arises in these conditions, reactive oxygen species have
This article has been cited by other articles:
 |
|
 |
|
  H. Tsutsui, S. Kinugawa, and S. Matsushima Mitochondrial oxidative stress and dysfunction in myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Suliman, M. S. Carraway, and C. A. Piantadosi Postlipopolysaccharide Oxidative Damage of Mitochondrial DNA Am. J. Respir. Crit. Care Med., February 15, 2003; 167(4): 570 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Madamanchi, C. Patterson, and M. S. Runge HIV Therapies and Atherosclerosis: Answers or Questions? Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1758 - 1760. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsutsui, T. Ide, T. Shiomi, D. Kang, S. Hayashidani, N. Suematsu, J. Wen, H. Utsumi, N. Hamasaki, and A. Takeshita 8-Oxo-dGTPase, Which Prevents Oxidative Stress-Induced DNA Damage, Increases in the Mitochondria From Failing Hearts Circulation, December 11, 2001; 104(24): 2883 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Grishko, M. Solomon, G. L. Wilson, S. P. LeDoux, and M. N. Gillespie Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1300 - L1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ide, H. Tsutsui, S. Hayashidani, D. Kang, N. Suematsu, K.-i. Nakamura, H. Utsumi, N. Hamasaki, and A. Takeshita Mitochondrial DNA Damage and Dysfunction Associated With Oxidative Stress in Failing Hearts After Myocardial Infarction Circ. Res., March 16, 2001; 88(5): 529 - 535. [Abstract] [Full Text] [PDF]
|
|