Low density lipoprotein metabolism by endothelial cells from human umbilical cord arteries and veins.

Abstract

Binding and metabolism of low density lipoprotein (LDL) and acetylated LDL were examined in endothelial cells from human umbilical cord arteries and veins. Both high and low affinity LDL interactions were observed. High affinity LDL binding and catabolism were increased five-to sevenfold after preincubation for 18 hours in LPDS containing medium. Subconfluent cells degraded, endocytosed, and bound 1.5 to 2.7 times more LDL by high affinity interaction than confluent cells, when endothelial cell growth supplement (ECGS) was present in the culture system. In the absence of ECGS, these ratios were somewhat less. Low affinity LDL metabolism was less affected by the state of confluency. Binding of LDL and acetylated LDL by venous endothelial cells was more than two-and threefold, respectively, than that by comparable arterial cells. However, the difference in LDL binding was not reflected in an altered LDL catabolism. There apparently is a population of low affinity binding sites not involved in LDL catabolism.LDL metabolism was identical in cells, which were cultured in medium supplemented with 20% to 100% serum or hirudin-or heparin-treated platelet-poor plasma. Without preincubation in LPDS, high affinity adsorptive endocytosis mediated the main part of LDL uptake only at low LDL concentrations (5 to 20 /ng protein/ml). However, at physiological LDL concentrations (550 ixg/m\), we estimated that this process mediated only 17% of the LDL uptake. We calculated that fluid endocytosis and low affinity adsorptive endocytosis of LDL accounted for the remaining 12% and 70%, respectively, of the LDL uptake at physiological LDL concentrations. (Arteriosclerosis 3:547-559, November/December 1983) L ow density lipoprotein (LDL) is a risk factor for atherosclerosis.1 The plasma level of LDL depends on the balance between its formation and its catabolism. To become catabolized, LDL has to enter or pass through the endothelium that lines the blood vessels. Only in the liver, bone marrow, and spleen does blood plasma have direct access to the tissue parenchymal cells via open fenestrations. 2Clearing by the liver accounts for 35% to 67% of the LDL removal in pigs, rabbits, and rats.3 " 6 Possibly, LDL also passes through the fenestrations of other visceral capillaries, e.g., those in the gut and the adrenal glands. However, the fenestrations in these tissues, which account for 10% to 15% of the LDL

VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: Involvement of the VLDL receptor

“…HUVEC express LDL and VLDL receptors, whereas only trace amounts of LRP have been demonstrated (27,41,42). In the present study, we confirm the expression of both LDL and VLDL receptors in HUVEC and also show, in accordance with studies in THP-1 cells (44), that the level of LDL receptors in HUVEC is suppressed in the presence of serum.…”

Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier

“…Primary cells are preferable to established brain endothelial cell lines, such as bEnd.3 cells, because several functional features and characteristics of endothelial cell lines are unlike those of primary cells (62,64). We used fluorescence microscopy to show that pmBECs passaged one time took up DiI-labeled acetylated low-density lipoprotein, an important functional characteristic of endothelial cells (data not shown) (73). Flow cytometric analysis was used to show that the pmBECs uniformly expressed high levels of CD31, ICAM, and VCAM, markers characteristic of endothelial cells (31), after one passage (data not shown).…”

Role of the low density lipoprotein receptor in penetration of low density lipoprotein into rabbit aortic wall.

“…Endothelial cells in culture express a functional LDL receptor. 15 - 19 Under conditions of tight confluency under some culture conditions, endothelial cells have reportedly suppressed essentially all LDL receptor expression. 16 - 19 However, recent studies from this laboratory provide evidence that in the rabbit aortic intima in vivo about 40% of the LDL degradation takes place via the high affinity receptor.…”

“…15 - 19 Under conditions of tight confluency under some culture conditions, endothelial cells have reportedly suppressed essentially all LDL receptor expression. 16 - 19 However, recent studies from this laboratory provide evidence that in the rabbit aortic intima in vivo about 40% of the LDL degradation takes place via the high affinity receptor. 12 However, these results relate only to those LDL molecules that enter the endothelial cell and go on to be degraded (measured by trapping of the covalently linked tyramine cellobiose marker).…”