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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of transmural pressure on low density lipoprotein and albumin transport and distribution across the intact arterial wall.

To investigate the effect of hyperpressure on the transport of low density lipoprotein (LDL) and albumin in the arterial wall, we measured in vitro the uptake of both iodine-131-labeled LDL and iodine-125-labeled albumin in intact rabbit thoracic aorta, held at in vivo length and pressurized to 70 or 160 mm Hg. Arteries were incubated for 2 hours (n = 8) at 70 mm Hg, and for 5 minutes (n = 4), 30 minutes (n = 4), 1 hour (n = 5), and 2 hours (n = 5) at 160 mm Hg. The transmural distribution of the relative concentrations of LDL (CLDL) and albumin (Calb) across the wall was determined by using a serial frozen sectioning technique. At 70 mm Hg, the mean medial CLDL and Calb values were 0.0018 +/- 0.0007 and 0.0039 +/- 0.0013, respectively. At 160 mm Hg, CLDL and Calb were markedly increased. The distribution of labeled albumin was almost uniform across the media and reached a steady state after 30 minutes, whereas labeled LDL accumulated in the first inner layers, a steady state being achieved after 1 hour. The 1-hour values of CLDL in the first and second luminal sections (0.24 +/- 0.03 and 0.13 +/- 0.05, respectively) were much higher than those of Calb, the CLDL/Calb ratios being 4.12 +/- 0.94 and 2.34 +/- 0.42 (p less than 0.01), respectively. In the subsequent sections, the CLDL decreased markedly and became much lower than the Calb, the CLDL/Calb ratio averaging 0.2 in the two-thirds outer media. To investigate whether LDL was trapped at high pressure in the inner layers, vessels were exposed to a tracer-free intraluminal solution for 30 minutes, after a 30-minute incubation with tracers. After washout, albumin was almost totally removed from the wall, while the CLDL were practically unchanged. Compaction of the media induced by high distending stresses applied to the vessel might have hindered the efflux of LDL, whereas albumin moved freely through the wall. Synergy between increased endothelial permeability and compaction of the media together with enhanced pressure-driven convection might account for the marked increase in LDL concentration observed in the inner wall at high pressure.[1]


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