Alterations in Internal Elastic Lamina Permeability As a Function of Age and Anatomical Site Precede Lesion Development in Apolipoprotein E–Null Mice

Early atherosclerosis is characterized by the accumulation of plasma-borne macromolecules (eg, low-density lipoproteins) in the arterial intima, which is bordered by endothelial cells (EC) and the internal elastic lamina (IEL). This accumulation is believed to be secondary to increased EC permeability. We hypothesized that a decrease in IEL permeability may precede lesion development and contribute to macromolecular accumulation. To test this hypothesis, we quantified EC and IEL permeability in lesion-free areas of the thoracic and abdominal aortas of chow-fed C57BL/6 control and atherosclerotic-prone apolipoprotein E (apoE)-null mice at 3 and 5 months of age. Between 3 and 5 months of age, apoE-null mice begin to develop atherosclerotic lesions in the thoracic aorta. No significant differences in EC and IEL permeability were observed at either time in C57BL/6 control mice. In contrast, 78% and 19% decreases in IEL permeability of the thoracic aorta and abdominal aorta, respectively, were observed between 3 to 5 months of age in apoE-null mice (thoracic: 2.05±1.33 and 0.44±0.15 μm/min, P P