Low‐Density Lipoprotein Receptor on Endothelium of Brain Capillaries

Abstract

The presence of lipoproteins, apolipoproteins, and their receptors in the brain could provide a system for cholesterol homeostasis, as they do in other tissues. This study was undertaken to determine whether plasma low-density lipoprotein, the major carrier of cholesterol, is involved in the delivery of lipids through the blood-brain barrier. 125I-Labeled low-density lipoprotein bound to a specific receptor on the endothelium of brain capillaries when it was injected immediately postmortem into bovine brain circulation. In contrast, no specific binding of 125I-low density lipoprotein was found when the incubations were performed with isolated capillaries. Incubations of endothelial or basement membranes of brain capillaries with 125I-low density lipoprotein demonstrated a high-affinity association of low-density lipoprotein with the membranes of bovine cerebral endothelial cells. The specificity of the low-density lipoprotein binding was determined in several ways using a dot blot assay. This receptor shows the same characteristics as the low-density lipoprotein receptor on human fibroblasts. The molecular weight of the bovine brain capillary low-density lipoprotein receptor (132,000) was determined by ligand blotting. These results demonstrated the occurrence of a low-density lipoprotein receptor on the endothelial cells of brain capillaries.

Expression of receptors for native and chemically modified low‐density lipoproteins in brain microvessels

“…astrocytes [36]) have been reported to affect the expression of both LDL-R and SCAV-Rs. Indeed, in confluent brain capillary Ecs, the LDL-R escapes the down-regulation mechanisms occurring in vascular Ecs of large vessels [16,36]. The expression of LDL-R and of SCAV-Rs is therefore likely to be modulated by cellular interaction occurring in brain microvessels, with possible variations in this interaction according to the experimental design, particularly in vitro.…”

“…The presence of tight junctions between the Ecs of brain microvessels and the low rate of pinocytosis and vesicular transport showed by these cells appear to be in fact the structural basis for its identification with the blood-brain barrier (BBB), which prevents passive diffusion of compounds from the blood into the brain and contributes to the maintenance of the homeostasis of brain interstitial fluid [14,15]. In particular, despite some evidence for the presence of LDL-R on the Ecs of brain capillaries [16], little is known about the presence of SCAV-Rs, and the conclusions appear uncertain.…”

Functional Protein Delivery into Neurons Using Polymeric Nanoparticles

“…Based on the observation that they absorb multiple proteins, particularly apolipoprotein E, onto their surfaces following injection into the bloodstream and that artificial coating of the particles with apolipoprotein E improves their uptake across the BBB, it was suggested that these NPs may be taken up via lipoprotein receptormediated endocytosis through mimicry of endogenous low density lipoproteins (LDLs) (12). Lipoprotein transport across the BBB is crucial for the delivery of essential lipids to brain cells, and direct evidence has been provided for the existence of a LDL receptor in vivo on the BBB (13). LDLs have further been shown to undergo transcytosis across the brain capillary endothelium without apparent degradation by endothelial cells, and they may therefore gain entry into other tissues following pas-sage across the BBB (14).…”

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

“…Recent studies demonstrated the transcytosis of LDL receptors in endothelial cells in the rat brain. [16][17][18] Therefore, cholesterol in vascular endothelial cells (VECs) in the brain is supplied/ maintained at a constant level via two pathways: the uptake of LDL-mediated cholesterol from the serum and the synthesis of cholesterol in VECs. Thus, lower cholesterol levels in the serum and the reduced biosynthesis of cholesterol by the brain may induce angionecrosis in the brain.…”