RATIONALE Plasma apolipoprotein (apo)M is mainly associated with high-density lipoprotein (HDL). HDL-bound apoM is antiatherogenic in vitro. However, plasma apoM is not associated with coronary heart disease in humans, perhaps because of a positive correlation with plasma low-density lipoprotein (LDL). OBJECTIVE We explored putative links between apoM and very-low-density (VLDL)/LDL metabolis...

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor, escorting it to its destruction in the lysosome and thereby preventing the recirculation of the low-density lipoprotein receptor to the hepatocyte cell surface. Both gain-of-function mutations in PCSK9 (causing marked increases in low-density lipoprotein cholesterol [LDL-C] concentration and pre...

We are studying the genetic factors underlying the common forms of heart disease by identifying genes that affect normal variations in plasma lipid, lipoprotein, and apolipoprotein concentrations in baboons. For these studies we are using cloned human gene probes to identify restriction fragment length polymorphisms (RFLPs) at loci encoding the proteins of cholesterol metabolism. In this report...

Two unrelated individuals were referred to Lipid Clinics in The Netherlands and Chile with extreme xanthomatosis and hypercholesterolemia. Both were diagnosed with heterozygous familial hypercholesterolemia (heFH) after molecular genetic analysis of the low-density lipoprotein (LDL) receptor gene. Since heFH by itself could not account for the massive xanthomas, the presence of an additional he...

The visible wavelength excited fluorophore 3,3'-dioctadecylindocarbocyanine iodide (Dil[3]) was incorporated into human low density lipoprotein (LDL) to form the highly fluorescent LDL derivative dil(3)-LDL. Dil(3)-LDL binds to normal human fibroblasts and to human fibroblasts defective in LDL receptor internalization but does not bind to LDL receptor-negative human fibroblasts at 4 degrees C o...

The interactions of low density lipoprotein (LDL) and apolipoprotein (apo) B-100 segments with chondroitin-6-SO4 rich aortic proteoglycans aggregate (CSPG) were studied by using quantitative frontal elution affinity chromatography. The affinity of the agarose-CSPG was higher for LDL than for very low density lipoprotein and high density lipoprotein was not bound. LDL from different individuals ...

DiI-LDL (3,3'-dioctadecylindocarbocyanine-low density lipoprotein) has been extensively used in morphological and microscopic studies of receptor-mediated metabolism of LDL in many cell lines. To date the use of this fluorescent probe in a quantitative assay of LDL receptor activity has not been widely used in studies with multiple samples due to the lack of a practical method for quantitativel...

OBJECTIVE Hepatic ATP binding cassette transporter A1 (ABCA1) expression is critical for maintaining plasma high-density lipoprotein (HDL) concentrations, but its role in macrophage reverse cholesterol transport and atherosclerosis is not fully understood. We investigated atherosclerosis development and reverse cholesterol transport in hepatocyte-specific ABCA1 knockout (HSKO) mice in the low-d...

When cultured human fibroblasts were incubated with medium of varying composition, the activity of the low density lipoprotein (LDL) receptor was strongly correlated with the amount of cholesterol that egressed from the cell. Particles isolated from lipoprotein-deficient serum (d > 1.25) by anti-apoprotein (apo) A-I affinity chromatography were as effective as the d > 1.25 serum in activating t...

Patients with familial hypercholesterolemia have elevated levels of plasma low density lipoproteins (LDL), increased hepatic synthesis of apolipoprotein B-containing lipoproteins, defective binding of low density lipoproteins to fibroblasts, and premature atherosclerosis. The role of a hepatic low density lipoprotein receptor in normal man and its importance in the pathogenesis of familial hype...