Studies of low density lipoprotein (LDL) metabolism in nonhuman model systems have indicated that the mammalian liver has dual mechanisms for the uptake and regulation of the concentration of plasma LDL. Heretofore, direct evaluation of lipoprotein uptake mechanisms in human hepatocytes has not been possible. In order to compare hepatocyte LDL uptake with fibroblast LDL metabolism, human hepato...

We previously demonstrated reduced levels of low density lipoprotein (LDL) cholesterol in association with increased total fractional catabolic rates (FCR( of LDL apoprotein B (apo B) in individuals with myeloproliferative diseases (MPD). The removal of LDL from plasma and interstitial fluid is mediated via receptor and nonreceptor pathways. We attempted to quantitate LDL catabolism via each of...

Combined treatment with trypsin, cholesterol esterase, and neuraminidase transforms LDL, but not HDL or VLDL, to particles with properties akin to those of lipid extracted from atherosclerotic lesions. Single or double enzyme modifications, or treatment with phospholipase C, or simple vortexing are ineffective. Triple enzyme treatment disrupts the ordered and uniform structure of LDL particles,...

Increasing evidence indicates that low density lipoprotein (LDL) has to be modified to induce foam cell formation. One such modification, oxidation of LDL, generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoprotein B. By immunizing animals with homologous malondialdehyde-modified LDL (MDA-LDL), 4...

Copper-oxidized LDL has many of the characteristics of the modified LDL generated in the artery wall during the initial stages of atherosclerosis. It is not, however, a chemically defined species but shows significant variations in both its chemical composition and behaviour in biological systems depending upon the extent to which the peroxidation reaction has occurred (Fig. 1). Taking care to ...

A key factor in atherosclerosis is the retention of low density lipoprotein (LDL) in the extracellular matrix of the arterial intima, where it binds to the negatively charged glycosaminoglycan chains of proteoglycans. Oxidation may lead to modification of the lysine residues of apolipoprotein B-100 of LDL, which normally mediate the binding of LDL to glycosaminoglycans. Here, we studied whether...

Low density lipoprotein (LDL) conditioned by incubation in the presence of rabbit aortic or human umbilical vein endothelial cells (endothelial cell-modified LDL) was degraded by macrophages three to five times more rapidly than LDL incubated in the absence of cells (control LDL). This enhanced degradation occurred mostly via a high affinity, saturable pathway related to the pathway for macroph...

Oxidative modification of LDL is causally involved in the development of atherosclerosis and occurs in vivo in the blood as well as within the vascular wall. The present study attempted to explore whether polyphenolic flavonoids influence monocyte-endothelium interaction and lectin-like oxidised LDL receptor 1 (LOX-1) expression involved in the early development of atherosclerosis. The flavones...