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

Area of Science:

• Environmental Health
• Cardiovascular Research
• Toxicology

Background:

• Over 100 million Americans live in areas exceeding ozone air quality standards.
• Ozone exposure is linked to cardiovascular events, but molecular mechanisms remain unclear.
• Pulmonary effects of ozone involve redox and immune responses.

Purpose of the Study:

• To investigate the molecular mechanisms of ozone-induced vascular impacts.
• To test the hypothesis that ozone inhalation causes vascular oxidant stress and mitochondrial dysfunction.
• To determine if ozone exposure influences atherogenesis.

Main Methods:

• Mice and infant macaque monkeys were exposed to cyclic, intermittent ozone or filtered air.
• Vascular tone, oxidant stress, mitochondrial DNA damage (mtDNA), and nitric oxide production were quantified.
• Atherosclerotic lesion formation was assessed in apoE-/- mice.

Main Results:

• Ozone exposure significantly altered vascular tone regulation.
• Increased vascular oxidant stress and mtDNA damage were observed.
• Decreased vascular endothelial nitric oxide synthase protein and nitric oxide production were noted.
• Ozone exposure significantly increased atherogenesis in apoE-/- mice.
• Vascular mtDNA damage in nonhuman primates mirrored human susceptibility to atherosclerosis.

Conclusions:

• Inhaled ozone, independent of other toxicants, promotes vascular dysfunction.
• Ozone exposure induces oxidative stress and mitochondrial damage in the vasculature.
• Ozone inhalation contributes to increased atherogenesis.