Exposure to UP is more closely related to the health effects than exposure to AP mass. The result of this Core will be a valuable input for the clinical, animal and in vitro studies with respect to planned mixed PM-oxidant exposures. These studies will make use of results from the field studies, starting initially with controlled exposures in healthy subjects and asthmatics, and then of elderly subjects with COPD and coronary artery disease, similar to the field study cohorts. Activation of vascular endothelium and circulating leukocytes. Emigration of inflammatory cells from blood to tissue sites involves upregulation of adhesion molecules and other markers on vascular endothelium and on circulating leukocytes.
Platelets become activated and adhere to endothelium and leukocytes.
Endothelial activation may further contribute to the increase in exhaled NO concentrations seen with airway inflammation. Increased release of IL-6 and tissue factor by activated blo ononuclear cells. Possible adverse cardiac events in patients with critical coronary lesions, as a consequence of increased blood coagulability, platelet activation, and endothelial dysfunction. The clinical studies will be extended by using rat models of human conditions including hypertension, sensitization and old age as well as transgenic mice to evaluate mechanistic hypothesis of PM induced pulmonary oxidative stress and its ramifications for cardiac and vascular events. The animal studies are designed to be complementary to the field and controlled clinical studies and to form a link to the mechanistic in vitro studies.