PURPOSE Modified (oxidized and/or glycated) low-density lipoproteins (LDLs) have been implicated in retinal pericyte loss, one of the major pathologic features of early-stage diabetic retinopathy. To delineate underlying molecular mechanisms, the present study was designed to explore the global effects of modified LDL on pericyte gene expression. METHODS Quiescent human retinal pericytes were...

Low density lipoprotein (LDL) isolated from human plasma anticoagulated with EDTA (EDTA/LDL) was 4-fold more resistant to oxidation by reagent H2O2, as assayed by the thiobarbituric acid (TBA) assay, than LDL prepared from plasma anticoagulated with citrate (CDP/LDL). The LDLs required 1-3 mM H2O2 for maximal oxidation by this assay, and ED50S were 1.7 X 10(-3) M for EDTA/LDL and 4.5 X 10(-4) M...

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...

The presence in plasma of an electronegative LDL subfraction [LDL(-)] cytotoxic for endothelial cells (ECs) has been reported. We studied the effect of LDL(-) on the release by ECs of molecules implicated in leukocyte recruitment [interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)] and in the plasminogen activator inhibitor-1 (PAI-1). LDL(-), isolated by anion-exchange chromatograp...

We investigated the interaction and transport of low-density lipoprotein (LDL) through the arterial endothelium in rat aorta and coronary artery, by perfusing in situ native, untagged human, and rat LDL. The latter was rendered electron-opaque after it interacted with the endothelial cell and was subsequently fixed within tissue. We achieved LDL electron-opacity by an improved fixation procedur...

Decreased plasma low density lipoprotein (LDL) particle size has been associated with premature coronary artery disease (CAD). We examined LDL particle size by 2-16% gradient gel electrophoresis in 275 men with CAD (>75% cross-sectional-area stenosis) and 822 controls. Seven major LDL size bands (with LDL-1 [d=1.025-1.033 g/ml] being the largest and LDL-7 [d= 1.050-1.063 g/ml, the smallest]) we...

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,...

By a recently developed sensitive density gradient ultracentrifugation method, the distribution of low density lipoprotein (LDL) subfractions was studied in the serum of healthy blood donors (20 to 62 years old). For each subject, we observed a specific LDL subfraction distribution characterized by the relative contribution of the three major LDL subfractions, LDL-1 (1.020 to 1.028 g/ml), LDL-2...

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...

BACKGROUND Plasma concentrations of small dense (sd)-LDL are associated with the prevalence of cardiovascular events. However, the special equipment and long assay times required for sd-LDL measurement have hindered its clinical application. Herein, we report development of a simple homogeneous assay for sd-LDL-cholesterol (C) adaptable to autoanalyzers. MATERIALS AND METHODS We identified su...