Atherogenesis, Transcytosis, and the Transmural Cholesterol Flux: A Critical Review

Figure 1

The entry of lipoproteins into the aorta wall. In all the examples below, the original authors concluded that lipoproteins enter the wall mainly from the lumen, but our alternative interpretation also fits the data. (a) The relative ([tissue]/[plasma]) concentration profile of radiolabeled cholesteryl ester in a pig aorta wall after administrating a pulse of differentially radiolabeled HDL and LDL either in vivo (left panel, 6.5 hours tissue exposure) or in situ into an isolated aortic segment (right panel, 4 hours tissue exposure). is the lumen-tissue slice distance, and is the wall thickness. The numbers 1-5 represent the aortic layers from the luminal to the adventitial side. The U-shaped concentration profile, spanning the entire wall thickness, is formed only in the in vivo experiment when lipoproteins can also enter the aorta wall through the vv. The minimal ability of LDL to penetrate the wall beyond the intima when the labeled lipoproteins cannot enter through the vv (right panel, bottom) is also evident. The observed “damming” of LDL at the intima-media boundary is attributed to the internal elastic lamina [57] but may represent the binding and trapping of LDL by intimal extracellular matrix proteins (adapted from Nordestgaard et al. [57]). (b) The relative ([tissue]/[plasma]) concentration profile of ¹²⁵I-labeled ApoB in the rabbit aorta wall 10 min. After an i.v. administration of iodinated LDL, is the lumen to mid-tissue slice distance, and is the lumen to medial-adventitial boundary distance. Each line represents a separate experiment. The transmural U-shaped concentration profile of ApoB, or its degradation products, is evident (adapted from Bratzler et al. [55]). (c) The fluorescence of FITC-labeled anti-LDL antibody in a section of rhesus monkey aorta wall 6 hours after administering 1gr/kg cholesterol by a gastric tube. The presence of the lipoprotein in the subendothelial and medial layers can be clearly seen by the greenish-yellow coloring of the tissues (adapted from Shimamoto et al. [60]).

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