Macromolecular Transport across Arterial and Venous Endothelium in Rats

Atherosclerotic lesions are characterized by llpid Infiltration in regions wtth high rates of endothellal cell turnover. The present investigation was designed to elucidate the route of macromolecular transport across vascular endothelium. The aorta and vena cava of male Sprague-Dawley rats were perfusion-flxed after the intravenous in|ection of Evans-blue albumin (EBA) or horseradish peroxidase (HRP). Fluorescence microscopic examination of en face preparation of the aorta stained with hematoxylln allowed the Identification of endothellal cells that underwent mitosis, together with the localization and quantification of fluorescent spots for EBA leakage. The HRP specimens were subjected to histochemicai treatment, and HRP leakage was seen as brown spots under the light microscope. Sliver nitrate stain was added In both EBA and HRP studies to outline cell boundaries and to visualize stigmata, stomata, and dead cells. In the aorta, almost every dividing cell showed Junctional leakage to albumin and HRP, with clustering of leaky spots around the branch orifices. Time-dependent studies showed gradual increases In the diameter and number of these heterogeneously sized leaky spots, which finally fused to sizes corresponding to the "blue areas" for EBA or "brown areas" for HRP. Compared wtth arteries, veins had fewer mltotlc cells, but more dead cells and diffuse dye-staining areas, Indicating a more rapid transport of macromolecules. The leaky spots In the artery were associated mainly with mltotic cells, dead cells, and stigmata, whereas those In the vein occurred primarily at regions with dead cells. These results suggest that the preferential association of the enhanced transport of macromolecules with mttosls In the arterial as compared to venous endothelium and the differential behavior In transmural transport between arteries and veins may form the basis for the predilection of atherosclerosis in arteries. (Arteriosclerosis 10:188-197, March/April 1990)