Traffic related air pollution has been associated with exacerbation of heart disease, specifically, it triggershospital admissions for heart attacks, irregular heart rhythms, episodes of heart failure and deaths from heartdisease. Diesel exhaust particles (DEP) is an important component of urban traffic related air pollutants. Theoverall objective of this study is to determine the effects of DEP exposure on blood vessels. Our broadhypothesize is that air pollutants impact blood vessels resulting in adverse cardiovascular health effects. Wepropose to use as well established model of DEP exposure of older Apo-E knock-out mice, mice thatnaturally develop atherosclerosis, the underlying disease resulting in heart attacks and stroke. This modelrepresents subjects at risk for the adverse effects of air pollution as shown in epidemiological studies,namely older subjects with pre-existing atherosclerosis. We will pursue the following specific aims: 1)Functional studies on the responses of blood vessels following DEP exposure. These studies involvedharvesting the aorta from mice exposed to DEP for 7 weeks and expose these vessels to different agonistand antagonist, measuring the ability of vessels to constrict and dilate. 2) Determine the different pathwaysactivated in the endothelium of blood vessels that could be involved in the abnormal functional response ofblood vessels following DEP exposure. 3) Measurement of circulating pro-inflammatory mediators that ininclude acute phase proteins, cytokines and leukocytes as well as vasoactive mediators such as Nitric Oxideand endothelins that has been implicated in abnormal vascular responses following air pollution exposure. 4)Quantitative histological studies to quantify the lung inflammation induced by DEP exposure as well as theparticle burden in the lung and relate these to the downstream abnormal vascular response of blood vessels.Numerous epidemiological studies have implicated exposure to air pollution particles to adverse effects onthe heart and blood vessels. The mechanisms how inhalation of particles into the lung impact blood vessels,are unclear and is the focus of this proposal. This research will advance our insights in how deposition of fineparticles in the lung results in adverse health effects such as triggering angina, a heart attack or stroke.Understanding these mechanisms could help to determine what potential therapeutic intervention couldprevent the adverse health effects of air pollutants on the heart and blood vessels.
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