This article is available online at http://www.jlr.org An increased low-density lipoprotein cholesterol (LDL-C) level is an established risk factor for cardiovascular disease. Statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) effectively reduce LDL-C levels and the risk of cardiovascular events ( 1 ). Statins also diminish infl ammation as indicated by a reduction of C-reactive prot...

Interferons have been shown to lower low density lipoprotein (LDL) cholesterol concentrations by 20-50%. To evaluate the effect of interferons on LDL metabolic behavior in individuals with normal and mildly elevated LDL cholesterol levels, autologous LDL labeled with 125I was administered to subjects at baseline and during interferon treatment. Interferon beta serine (IFN-beta serine) was admin...

Endothelial dysfunction, or activation, elicited by oxidized low density lipoprotein (Ox-LDL) and its lipid constituents has been shown to play a key role in the pathogenesis of atherosclerosis. We recently have identified a novel receptor for Ox-LDL-designated lectin-like Ox-LDL receptor (LOX-1) in vascular endothelial cells. To examine ligand specificity of LOX-1, we established CHO cell line...

Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction pr...

In subject with heterozygous familial hypercholesterolemia (FH), a 50% deficiency of receptors for plasma low density lipoprotein (LDL) impairs the removal of LDL from plasma and produces hypercholesterolemia. In these patients mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, blocks cholesterol synthesis and lowers plasma LDL levels. To determine the mechanism for the LDL-lo...

The early atherosclerotic lesion is comprised of foam cell macrophages filled with cholesteryl ester (CE), unesterified cholesterol (UC), and cholesterol oxides. Upon incubation of macrophages with oxidized low density lipoprotein (Ox-LDL), they accumulate UC rather than CE, which was shown to accumulate after incubation of cells with acetylated LDL (Ac-LDL). Using lipoproteins that were doubly...

Incubation of mouse peritoneal macrophages with native human low density lipoprotein (LDL) did not cause any significant storage of intracellular cholesteryl esters. However, when the LDL was subjected to brief (30-second) vortexing, it formed self-aggregates that were rapidly ingested and degraded by macrophages, converting them to cholesteryl ester-rich foam cells. Such aggregates were as pot...

Versican-like proteoglycans are the main component of the intimal extracellular matrix interacting with low density lipoprotein (LDL). The aim of this study has been to investigate the receptors involved in versican-modified LDL uptake by human vascular smooth muscle cells (VSMCs). We have found that versican-LDL interaction leads to the following: (1) monomeric LDL particles that are similar i...

Electronegative low density lipoprotein (LDL(-)) formation that structurally resembles LDL(-) isolated from plasma was evaluated after LDL treatment with snake venom phospholipase A(2) (PLA(2)). PLA(2) treatment of LDL increased its electrophoretic mobility in proportion to the amount of LDL(-) formed without evidence of lipid peroxidation. These changes dose-dependently correlated with the deg...

OBJECTIVE LDLs include particle subclasses that have different mobilities on polyacrylamide gradient gels: LDL-I (27.2 to 28.5 nm), LDL-IIa (26.5 to 27.2 nm), LDL-IIb (25.6 to 26.5 nm), LDL-IIIa (24.7 to 25.6 nm), LDL-IIIb (24.2 to 24.7 nm), LDL-IVa (23.3 to 24.2 nm), and LDL-IVb (22.0 to 23.3 nm in diameter). We hypothesized that the association between smaller LDL particles and coronary arter...