The pulmonary and cardiovascular effects of chronic exposure to nanomaterials, emphasis on inflammation and atherosclerosis.

In general, the conceptual objective of the study is that pulmonary exposure to engineered nanoparticles (NPs) may induce systemic effects which are relevant to atherogenesis or the progression of atherosclerosis. The toxicological testing of NPs will include physico-chemical characterization of nanomaterials used, in vitro assays, and in vivo studies. All exposures will be performed using low concentrations of NPs and, when applicable, chronic exposure will be performed. In vitro studies in this project will focus on the mechanistic aspects of endothelial dysfunction upon pulmonary exposure. For this purpose, a multicellular in vitro model of the alveolar-capillary barrier will be applied. In vivo, effects of low-concentration chronic exposure NPs on the risk of cardiovascular diseases will be studied by means of healthy and genetically altered animal experimental models, as the exposure to low doses of these materials may modify the progression of existing pathophysiological conditions including cardiovascular diseases, e.g. ApoE+/+ mice and ApoE-/- transgenic mice (one of the widely used model of human atherosclerosis). Animals will be exposed to NPs via pharyngeal aspiration. We will evaluate the cardiovascular effects resulting from pulmonary exposure including vascular inflammation, blood coagulation status, progression of atherosclerosis, as well as related mechanisms associated with respiratory exposure including generation of reactive oxygen species, expression of adhesion molecules and cytoskeleton changes in endothelial cells.

Keywords:Nanomaterials, Nanoparticles, Chronic exposure, In vitro, In vivo, Inflammation, Endothelial dysfunction, Atherosclerosis

Disciplines:Public health care