Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis.
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.
Chuang
Gin C
GC
Department of Pathology, University of Alabama at Birmingham, USA.
Yang
Zhen
Z
Westbrook
David G
DG
Pompilius
Melissa
M
Ballinger
Carol A
CA
White
C Roger
CR
Krzywanski
David M
DM
Postlethwait
Edward M
EM
Ballinger
Scott W
SW
D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D006339:Heart Rate / Q000502:physiology; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects; D018384:Oxidative Stress / Q000502:physiology; D010126:Ozone / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000393:Air Pollutants; D004272:DNA, Mitochondrial; D009566:Nitrates; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites; D016877:Oxidants; D010126:Ozone; D013482:Superoxide Dismutase; D014443:Tyrosine; D000099156:Superoxide Dismutase 2; C002744:3-nitrotyrosine; C496315:Nos3 protein, mouse