Progression of atherosclerotic plaques in the aorta and brachiocephalic artery from <i>ApoE</i>^<i>-/-</i> mice exposed to carbon black (CB) and/or lipopolysaccharide (LPS) by i.t. instillation.

<p>A) Atherosclerotic plaque area is expressed as the percentage of the luminal surface of the aorta covered with plaques. Calculations were made on whole aorta preparations from ascending aorta to the iliac bifurcation. B) Atherosclerotic plaque area expressed as the percentage of the lumen occupied by plaques in BCA. Six sections of BCA per animal were analyzed; three sections at 100 μm and three sections at 200 μm after the branch from the aortic arch (n = 6–10 mice per group). C) The intima-media ratio in BCA is calculated by dividing the area of the intima with the area of the media layer (n = 6–10 mice per group). Black bars represent the groups that did not receive LPS and white bars the groups that did receive LPS. Minus (-) denotes no exposure, plus denotes low (+) or high-dose (++) exposure. Data are presented as mean and SEM. Asterisks denote statistical significance *P<0.05, using one-way ANOVA with Tukey’s post-hoc test, and **P<0.01, two-factor ANOVA with Fisher’s LSD post-hoc test.</p

Serotonin receptor antagonist inhibition of plasma-mediated vasomotor contraction in aorta rings.

<p>The figure shows two graphical illustrations of the vasomotor function in real-time recorded in Lab Chart 8 myograph module (ADInstruments & DMT). A) 1% plasma from CB-exposed <i>ApoE</i>^<i>-/-</i> mice causes contraction of the naïve aorta ring segment. The addition the serotonin receptor antagonist Ketanserin (0.1 μM) on the plateau of the constriction response releases the plasma-mediated contraction. B) 17 min pre-incubation with Ketanserin (0.1 μM) inhibits the 1% plasma-mediated vessel contraction. Stimulation of the adrenergic receptors in the naïve aorta ring segments with Phenylephrine (10 μM), demonstrates that the artery has preserved the ability for receptor-mediated contraction via a receptor not specific for serotonin. The findings presented in the figure was reproduced in 3 different mice (n = 3) with the same result.</p

BALF cell number and distribution at 24 h post-exposure after repeated i.t. instillations of carbon black (CB) and/or lipopolysaccharide (LPS) in <i>ApoE</i>^<i>-/-</i> mice.

<p>BALF cell number and distribution at 24 h post-exposure after repeated i.t. instillations of carbon black (CB) and/or lipopolysaccharide (LPS) in <i>ApoE</i>^<i>-/-</i> mice.</p

Glutathione status in lung tissue of <i>ApoE</i>^<i>-/-</i> mice after repeated i.t. instillations of carbon black (CB) or lipopolysaccharide (LPS).

<p>Total and reduced glutathione was measured at 24 h post-exposure in lung homogenate from <i>ApoE</i>^<i>-/-</i> mice of study 1 and 2. Data is presented as mean and SEM (n = 10 mice per group).</p

Vasoconstriction in response to vasoactive mediators in plasma from <i>ApoE</i>^<i>-/-</i> mice.

<p>Vasoconstriction in response to vasoactive mediators in plasma from <i>ApoE</i>^<i>-/-</i> mice.</p

Plaque classification score in brachiocephalic arteries from <i>ApoE</i>^<i>-/-</i> after repeated i.t. instillations of carbon black (CB) and/or lipopolysaccharide (LPS).

<p>Plaque classification score in brachiocephalic arteries from <i>ApoE</i>^<i>-/-</i> after repeated i.t. instillations of carbon black (CB) and/or lipopolysaccharide (LPS).</p

Atherosclerosis and vasomotor dysfunction in arteries of animals after exposure to combustion-derived particulate matter or nanomaterials

<p>Exposure to particulate matter (PM) from traffic vehicles is hazardous to the vascular system, leading to clinical manifestations and mortality due to ischemic heart disease. By analogy, nanomaterials may also be associated with the same outcomes. Here, the effects of exposure to PM from ambient air, diesel exhaust and certain nanomaterials on atherosclerosis and vasomotor function in animals have been assessed. The majority of studies have used pulmonary exposure by inhalation or instillation, although there are some studies on non-pulmonary routes such as the gastrointestinal tract. Airway exposure to air pollution particles and nanomaterials is associated with similar effects on atherosclerosis progression, augmented vasoconstriction and blunted vasorelaxation responses in arteries, whereas exposure to diesel exhaust is associated with lower responses. At present, there is no convincing evidence of dose-dependent effects across studies. Oxidative stress and inflammation have been observed in the arterial wall of PM-exposed animals with vasomotor dysfunction or plaque progression. From the data, it is evident that pulmonary and systemic inflammation does not seem to be necessary for these vascular effects to occur. Furthermore, there is inconsistent evidence with regard to altered plasma lipid profile and systemic inflammation as a key step in vasomotor dysfunction and progression of atherosclerosis in PM-exposed animals. In summary, the results show that certain nanomaterials, including TiO₂, carbon black and carbon nanotubes, have similar hazards to the vascular system as combustion-derived PM.</p