HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/L209    most recent 00102.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Chuang, G. C. Articles by Ballinger, S. W. PubMed PubMed Citation Articles by Chuang, G. C. Articles by Ballinger, S. W.

EDITORIAL FOCUS

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

¹Department of Pathology, Division of Molecular and Cellular Pathology, ²Center for Free Radical Biology, ³Department of Environmental Health Sciences, and ⁴Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 27 March 2009 ; accepted in final form 22 April 2009

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.

environmental oxidants; atherosclerosis; mitochondria; mitochondrial DNA damage; mice; nonhuman primates; lung; oxidative stress; nitric oxide

This article has been cited by other articles:

				M. S. Hazari, N. Haykal-Coates, D. W. Winsett, D. L. Costa, and A. K. Farraj A Single Exposure to Particulate or Gaseous Air Pollution Increases the Risk of Aconitine-Induced Cardiac Arrhythmia in Hypertensive Rats Toxicol. Sci., December 1, 2009; 112(2): 532 - 542. [Abstract] [Full Text] [PDF]

				M. P. Cole and B. A. Freeman Promotion of cardiovascular disease by exposure to the air pollutant ozone Am J Physiol Lung Cell Mol Physiol, August 1, 2009; 297(2): L205 - L208. [Full Text] [PDF]