Regional variations in endothelial permeability to 125I-low density lipoproteins in rabbit arteries

The permeability of the arterial wall to macromolecules is not uniform, and focal regions of clevated permeability may represent the initial stages of atherosclerosis. Hypothesis to explain the focal nature of high permeability regions include distention of the arterial wall during the cardiac cycle, the local hemodynamic environment, endothelial cell death, and endothelial cell replication. En face autoradiography of the endothelium was used to examine regional variations in 125I-low density lipoprotein (LDL) permeability in the arrerial wall in vivo. Rabbits were injected with 125I-LDL and sacrificed after 10 min. Endothelial preparations from fixed arterial tissue were dipped in nuclear emulsion, exposed for 4-6 weeks, developed and stained with hematoxylin. Radioactive calibration standards consisting of known concentrations of 125I-albumin were processed with the tissue. For regions of uniformly low grain density in the rabbit aorta, the 125I-LDL permeability was 1.4 ± 0.5 × 10-8 cm/s and the average diffusion coefficient was 0.64 ± 0.21 × 10-10 cm2/s. Errors in the estimated permeability arising from nonuniformities in tissue thickness were the same as the reported experimental variability. Regions of elevated permeability ranged in size from 100 to 6,000 μm2 with permeabilities 4 to 40 times greater than the permeability in surrounding regions (average: 41 ± 24 × 10-8 cm/s). The frequency of elevated regions of permeability was highest in the arch, thoracic aorta, and carotid artery, and was significantly lower in the abdominal aorta and femoral arteries. Approximately 60% of the mitotic cells showed increased permeability to LDL but these mitotic cells accounted for only 40% of the regions of elevated permeability. Regions of highest permeability were associated with the mitotic cells.