Ultrastructural changes in atherosclerotic plaques following the instillation of airborne particulate matter into the lungs of rabbits

Understanding Human Illness and Death Following Exposure to Particulate Matter Air Pollution

“…Work done by our laboratory at the James Hogg Research Center showed structural changes in atherosclerotic plaques from Watanabe Heritable Hyperlipidemic (WHHL) rabbits exposed to PM 10 (Suwa et al, 2002;Tranfield et al, 2010;Yatera et al, 2008) and from ApoE -/-mice exposed to diesel exhaust (Bai et al, 2011). The observed changes were consistent with atherosclerotic plaques vulnerable to rupture.…”

“…Our electron microscopy studies showed three critical findings: 1. an accumulation of macrophage-derived foam cells immediately below the endothelium of atherosclerotic plaque cores, 2. the separation of the endothelium from a previously undescribed reticulum of dense extracellular matrix (ECM) that serves as the supporting layer of atherosclerotic plaques, and 3. evidence of degradation or fragmentation of the dense ECM in regions of macrophage-derived foam cell accumulation (Tranfield et al, 2010). As a consequence of fragmentation of the ECM, there was increased direct contact between macrophage-derived foam cells and the endothelial cells.…”

“…Furthermore, increased macrophage-derived foam cell migration was observed over the core regions of atherosclerotic plaques from PM 10 exposed rabbits. The evidence suggests that the cells were emigrating out of the atherosclerotic plaques and into the lumen of the aorta (Tranfield et al, 2010).…”

“…Quantification of these observations found that in PM 10 exposed rabbits, 21.6% of the endothelial cell contacts were with fragmented ECM, whereas only 8.4% of endothelial contacts in control rabbits were in contact with fragmented ECM (p < 0.0001). The number of endothelial cell contacts with macrophage-derived foam cells was found to be 13.4% in the control rabbits and increased significantly to 38.1% in PM 10 exposed rabbits (p = 0.0039) (Tranfield et al, 2010). To better understand changes in the contact between the dense ECM and the endothelial cells, serial thin section reconstructions were done using transmission electron microscopy ( Figure 3).…”

Nitrative stress, oxidative stress and plasma endothelin levels after inhalation of particulate matter and ozone

“…In this study, we investigated the impact of inhaled ozone, airborne particles and the mixtures on nitrative stress, oxidative stress and circulating endothelin levels in experimental animals. The urban air particle EHC-93 has been used widely as a model particle in air pollutant toxicity investigations [ 8 , 21 , 24 – 26 ]. As discussed before, while the absolute concentration of the total suspended particulate matter is high relative to PM 2.5 levels in North America, the alveolar deposited dose of fine particulate mass is within an order of magnitude of realistic human exposure scenario.…”