Extramural Research
Presentation Abstract
Grantee Research Project Results
Mark W. Frampton
University of Rochester, Rochester, NY
NIEHS Grant Number: 1R01ES013394-01
Project Description:
Exposure to ambient air particulate matter is associated with increased
risk for cardiovascular disease. UItrafine particles (UFP) may be important
in this regard because of their high surface area, oxidant capacity, and
ability to enter the lung interstitium and vascular space. These studies
will test the hypothesis that exposure to ambient UFP causes endothelial
dysfunction in both the pulmonary and systemic vascular beds, via oxidant
mechanisms. The investigators will determine whether people with type
2 diabetes, who have underlying vascular dysfunction related to oxidative
stress, will be more susceptible than healthy subjects to the acute vascular
effects of UFP exposure. These studies will consist of three human exposure
protocols, using the Harvard Ultrafine Ambient Particle Concentrator.
The first protocol will examine effects in healthy subjects, the second
protocol will examine effects in age-matched subjects with type 2 diabetes,
and the third protocol will assess the role of supplementation with antioxidant
vitamins C and E in preventing the vascular effects of UFP exposure. Pulmonary
vascular effects will be assessed by changes in the diffusing capacity
for carbon monoxide, and the pulmonary capillary blood volume. Systemic
vascular effects will be measured using forearm flow-mediated dilatation,
with and without nitroglycerin. In addition, the investigators will measure
the oxidant capacity of the concentrated ultrafine aerosol, and the level
of systemic oxidative stress using glutathione redox balance and plasma
lipid peroxides. Confirmation of the hypothesis that UFP oxidant capacity
mediates vascular effects will have important implications for air pollution
regulatory efforts, and will provide new approaches for the prevention
of cardiovascular health effects.