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Cardiovascular health effects of paint dust with and without nanoparticles compared to the primary nanoparticles


Lone Mikkelsen


A number of studies on ambient air particles as well as a few studies on engineered nanoparticles(NPs) have indicated associations between exposure and risk of cardiovascular events. Inhalationof NPs may elicit pulmonary inflammation followed by an increased release of cytokines, whichmight further affect the function of endothelial cells and development of atherosclerosis. Theendothelium is a key regulator of vascular homeostasis, functioning as a physical barrier and anactive signal transducer. This monolayer responds to both physical and chemical signals byproducing factors that regulate vascular tone, cellular adhesion, and vessel wall inflammation. Theexpression of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1(VCAM-1) on the membrane of endothelial cells is an early event in atherosclerosis.It is the small size of NPs that provide unique properties and also causes concern about possibletoxicological effects. Paints and lacquers are examples of products containing particulate matter,where NPs can be added to provide special properties such as resistance to bleaching by sunlight.NPs undoubtedly have many benefits in consumer and industrial products, but their potentialhealth effects are not yet fully understood. The production, use, and removal of paints give rise todifferent exposure situations where NPs may occur as primary nanosized particles or embedded ina matrix with larger particles. NPs might also be released and potentially inhaled by sanding ofsurfaces with NP-containing paint.The aim of this thesis was to investigate the effect of exposure to primary NPs and grinded paintdust samples on vascular function in cultured human umbilical vein endothelial cells (HUVECs)and dyslipidemic apolipoprotein E (ApoE-/-) knockout mice that are susceptible to the developmentof atherosclerosis.HUVECs were exposed to a panel of 22 different samples of primary NPs and dust samples fromgrinded paint with and without NPs. The primary NPs included TiO2 and carbon black, togetherwith samples of fillers and binders, which were also investigated in order to evaluate the effect ofother particles than pigments in paints. A detailed physicochemical characterization of the samplesutilized in this study was performed in order to uncover characteristics that might be importantdeterminants for toxicological effects in cultured cells or animal tissues. Primary TiO2 and carbonblack (Flammrüss 101) particles increased the production of reactive oxygen species (ROS) andexpression of cell adhesion molecules VCAM-1 and ICAM-1 in HUVECs, whereas paint dust withand without NPs had substantially lower effects on mass basis. Samples of binders and fillers inpaint also increased ROS producing ability and expression of cell adhesion molecules in HUVECs.The magnitude of cell adhesion molecule expression was not dependent on the particle size of thesuspension, determined by dynamic light scattering.The effect on vasomotor function and progression of atherosclerosis was assessed inatherosclerosis-prone ApoE-/- mice exposed to three different types of primary TiO2 particles byintratracheal instillation. The mice were pulmonary exposed to two intratracheal instillations of 0.5mg/kg bodyweight of fine-sized (21 m2/g), photocatalytic (17.8 m2/g), or nanosized (107.7 m2/g)TiO2 at 26 and 2 hours before sacrifice. There were no effects on endothelium-dependent orendothelium-independent vasodilation in aorta segments mounted in a myograph. However,intratracheal instillation of nanosized TiO2 (0.5 mg/kg bodyweight) once a week for four weeks wasassociated with a modest increase in plaque progression in the aorta.