Evidence suggests a possible role for human cytomegalovirus (HCMV) in the development of arteriosclerosis. One of the earliest events in plaque formation is the accumulation of lipid-laden foam cells, derived from macrophages and smooth muscle cells (SMCs). The lipid accumulation that occurs depends upon the uptake of oxidized LDL (OxLDL), a process in which the scavenger receptor (SR) has been...

The low density lipoprotein (LDL) receptor mediates the cellular uptake of plasma lipoproteins that are derived from very low density lipoproteins (VLDL). Most of the functional LDL receptors in the body are located in the liver. Here, we describe a radionuclide scintiscanning technique that permits the measurement of LDL receptors in the livers of intact rabbits. 123I-labeled VLDL were adminis...

The hypothesis that oxidized LDL (ox-LDL) is necessary, if not obligatory, in the development of atherosclerotic lesions was formulated .20 years ago with the seminal observation that uptake of native LDL by macrophages did not result in foam cell formation. In contrast, uptake of ox-LDL via scavenger receptors resulted in the unregulated accumulation of lipid.1 Since then, multiple studies in ...

Reduction of the blood levels of low density lipoprotein (LDL) is important for lowering the incidence of atherosclerosis. In this study, LDL was directed to rat parenchymal liver cells by lactosaminated Fab fragments of anti-apolipoprotein B antibodies (LacFab). We followed the fate of intravenously injected complexes of LacFab and [3H]cholesteryl oleate-labeled LDL. Complexing of LacFab to LD...

We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseu...

Platelet secretory products were shown to modulate the interaction between lipoproteins and their receptors on macrophages. Preincubation of macrophages for 2 h at 37°C with platelet conditioned medium (PCM), followed by its removal and a further 5-h incubation in the presence of oxidized-LDL (Ox-LDL), resulted in increased cellular degradation of Ox-LDL (34%), stimulation of cellular cholester...

Pharmacology: Rosuvastatin selectively and competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in the production of mevalonate, a cholesterol precursor. Rosuvastatin has high activity in, uptake into, and selectivity for the liver, the target organ. It enhances uptake and catabolism of LDL by increasing hepatic LDL receptor levels. It also inhibits the hepatic VLDL synthesis, red...

Receptor-independent low density lipoprotein (LDL) transport plays a critical role in the regulation of plasma cholesterol levels; hence, these studies were done to characterize this process in the tissues of the rat. High rates of receptor-independent clearance were found in the spleen, but other organs, like liver, gastrointestinal tract, and endocrine glands manifested lower clearance rates ...

A human monocytic cell line, THP-1, stimulated with 40 nM phorbol myristate acetate (PMA), differentiated to macrophage-like cells, and exhibited increased expression and release of interleukin-1 beta and expression of acetylated low density lipoprotein (ac-LDL) receptors. A selective inhibitor, MDL 29,152 (4-propyl-5-(4-quinolinyl)-2(3H)-oxazolone) was used to show that this induction required...

THE PROCESS of cellular uptake and metabolism of cyclosporine (CsA) is poorly understood. Earlier studies in this laboratory indicated that transport of CsA in blood occurs in association with plasma lipoproteins, with low density lipoprotein (LDL) and high density lipoprotein (HOL) carrying about 32% each of the total CsA in blood. This observation suggests the possibility that the cellular up...