Mechanisms for Cardiovascular Effects of air pollutants: Effect of Age and Sex

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DESCRIPTION (provided by applicant): Since the 1970's, adverse health effects have been reported at unexpectedly low levels of particulate air pollution, leading scientists and public health officials to conclude that long-term exposure to combustion-related fine particulate air pollution is a significant environmental risk factor for heart and lung diseases. Despite numerous studies examining the effects of petroleum diesel (petrodiesel) exhaust emissions on the respiratory system, the mechanisms responsible for the reported adverse human health effects and pinpointing the particulate's toxic initiating species remain elusive. Biodiesel fuel made from vegetable oil or animal fat is gaining momentum as the energy source of the future both in the U.S. and Europe. Biodiesel is typically blended into conventional diesel fuel, and emission testing has shown that biodiesel emissions appear to contain reduced levels of hydrocarbons, carbon monoxide and particulate matter (PM) but a higher soluble organic fraction in the particulate phase. Advancing age is a known risk factor for atherosclerosis, and sex differences in cardiovascular disease (CVD), autoimmune disease and airway hypersensitivity have been reported. With increased evidence that air pollutants act to exacerbate CVD, it is important to determine the mechanisms responsible for the exacerbation of atherosclerosis and the influence of age and sex on the responses to inhaled particles on underlying CVD. The hypothesis to be tested is that particulate and gaseous emissions from biodiesel compared to petrodiesel combustion will differ in the extent of lung injury and adverse systemic inflammatory responses. This will lead ultimately to different degrees of exacerbation of atherosclerosis, which will be modulated by the age and sex of the animal. This proposal will establish controlled production of engine emissions to be used in inhalation studies. The particulate and gaseous components of the exhaust as well as the heterogeneous oxidation products upon reaction with ozone will be characterized. Using animal models of disease, we will identify key signaling pathways and inflammatory responses in the lung after 3- and 9-day exposures to engine exhaust and specific gaseous and particulate size fractions, quantify and determine the types of cells (e.g. dendritic cells, alveolar macrophages, CD4+ T cells) induced after exposures to engine exhaust, and determine the effects of chronic exposure to exhaust on the development of atherosclerosis in mice with a specific focus on modulation by the age and sex of the animals. These approaches will provide insight into susceptibility of vulnerable populations (women and the elderly) and approaches for intervention and therapy. PUBLIC HEALTH RELEVANCE: Biodiesel has been touted as an important strategy for energy independence as well as sustainability in terms of agricultural production and reduced environmental impact from the transportation sector, but as with petrodiesel, combustion of biodiesel produces particulate air pollution. Adverse health effects of airborne particulate matter (PM) have been reported at unexpectedly low concentrations, leading scientists and public health officials to conclude that long-term exposure to combustion-related particulate air pollution is a significant environmental risk factor for heart and lung diseases. Despite the belief that biofuels may be better for the environment and for human health, there is very limited information about the biological effects of biodiesel emissions so this proposal will compare and contrast the biological effects of emission particles from the combustion of petro- and biodiesel and the influence of age and gender on these responses in an effort to lay the groundwork for future studies aimed at elucidating the mechanisms responsible for the significant relationship between airborne PM and lung and heart disease and at developing approaches to reduce the adverse health consequences of air pollution.