Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis

Gin C. Chuang, Zhen Yang, David G. Westbrook, Melissa Pompilius, Carol A. Ballinger, C. Roger White, David M. Krzywanski, Edward M. Postlethwait, Scott W. Ballinger

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


More than 100 million people in the United States live in areas that exceed current ozone air quality standards. In addition to its known pulmonary effects, environmental ozone exposures have been associated with increased hospital admissions related to cardiovascular events, but to date, no studies have elucidated the potential molecular mechanisms that may account for exposure-related vascular impacts. Because of the known pulmonary redox and immune biology stemming from ozone exposure, we hypothesized that ozone inhalation would initiate oxidant stress, mitochondrial damage, and dysfunction within the vasculature. Accordingly, these factors were quantified in mice consequent to a cyclic, intermittent pattern of ozone or filtered air control exposure. Ozone significantly modulated vascular tone regulation and increased oxidant stress and mitochondrial DNA damage (mtDNA), which was accompanied by significantly decreased vascular endothelial nitric oxide synthase protein and indices of nitric oxide production. To examine influences on atherosclerotic lesion formation, apoE-/-mice were exposed as above, and aortic plaques were quantified. Exposure resulted in significantly increased atherogenesis compared with filtered air controls. Vascular mitochondrial damage was additionally quantified in ozone- and filtered air-exposed infant macaque monkeys. These studies revealed that ozone increased vascular mtDNA damage in nonhuman primates in a fashion consistent with known atherosclerotic lesion susceptibility in humans. Consequently, inhaled ozone, in the absence of other environmental toxicants, promotes increased vascular dysfunction, oxidative stress, mitochondrial damage, and atherogenesis.

Original languageEnglish (US)
Pages (from-to)L209-L216
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2
StatePublished - Aug 2009
Externally publishedYes


  • Atherosclerosis
  • Environmental oxidants
  • Lung
  • Mice
  • Mitochondria
  • Mitochondrial DNA damage
  • Nitric oxide
  • Nonhuman primates
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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