The goal of this study was to understand why the expression of low density lipoprotein (LDL) receptors by the liver is poorly down-regulated by cholesterol. We examined the hypothesis that 7 alpha-hydroxylase may indirectly induce the expression of the LDL receptor by metabolizing, i.e. inactivating oxysterol repressors. Non-hepatic Chinese hamster ovary cells, transfected with a plasmid encodi...

Oxidative modification of lipoproteins is believed to be important in the genesis of atherosclerosis. We established cultures of smooth muscle cells (SMC) and exposed them to native LDL or oxidized LDL. Oxidized LDL, but not native LDL, was mitogenic as measured by incorporation of [3H]-thymidine into DNA. This effect was concentration dependent, averaged 288% of control, and was blocked by a p...

The structure and processing of low density lipoprotein (LDL) receptors in wild-type and LDL receptor-deficient mutant Chinese hamster ovary cells was examined using polyclonal anti-receptor antibodies. As previously reported for human LDL receptors, the LDL receptors in wild-type Chinese hamster ovary cells were synthesized as precursors which were extensively processed by glycosylation to a m...

The aim of this work was to investigate the possible mechanisms for uptake by human monocyte-derived macrophages (HMDM) of low density lipoprotein (LDL) pretreated with human arterial chondroitin-6-SO4-rich proteoglycan (LDL-PG). HMDM were incubated with 125I-labeled tyramine cellobiose-labeled LDL-PG, native LDL, and acetylated LDL (Ac-LDL). The results showed that two to four times more LDL-P...

Self-aggregates of low density lipoprotein (LDL) are taken up and degraded more rapidly by macrophages than is native LDL. That enhanced uptake is attributable in part to phagocytosis via the LDL receptor pathway. However, arterial macrophages appear to express little LDL receptor activity. The present studies demonstrate an alternative mechanism by which LDL aggregates could contribute to foam...

Elevated plasma levels of cytokines have been demonstrated in inflammatory, malignant, and infectious diseases. These disease states are often associated with abnormal lipid metabolism and reductions in plasma cholesterol levels. To determine if inflammatory cytokines could influence hepatic lipid metabolism, we evaluated low density lipoprotein (LDL) receptor function and gene expression in cy...

Familial hypercholesterolemia is an autosomal dominant disorder with a gene-dosage effect that is usually caused by mutations in the LDL receptor gene that disrupt normal clearance of LDL. In the homozygous form, it results in a distinctive clinical phenotype, characterized by inherited hypercholesterolemia, cholesterol deposition in tendons, and severe premature coronary disease. We described ...

The Lpb5 apolipoprotein B (apoB) allele occurs in pigs with spontaneous hypercholesterolemia. Low-density lipoprotein (LDL) from these pigs binds to the LDL receptor with a lower affinity and is cleared from the circulation more slowly than control pig LDL. However, the severity of hypercholesterolemia in pigs with the mutant apoB allele is highly variable. This study aimed to determine the met...

OBJECTIVE Although inflammation is a recognized feature of atherosclerosis, the impact of inflammation on cellular cholesterol homeostasis is unclear. This study focuses on the molecular mechanisms by which inflammatory cytokines disrupt low-density lipoprotein (LDL) receptor regulation. METHODS AND RESULTS IL-1beta enhanced transformation of vascular smooth muscle cells into foam cells by in...