Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.
Mutations in another genetic locus, the low density lipoprotein (LDL) receptor gene, give rise to familial hypercholesterolemia (FH), a disease characterized by hypercholesterolemia, tendon xanthomas and atherosclerosis.
We compare the nucleotide sequences of the region encompassing the putative LDL receptor-binding sites from four pig alleles, including one implicated directly in atherosclerosis.
A six-year-old girl with severe hypercholesterolemia and atherosclerosis had two defective genes at the low-density-lipoprotein (LDL) receptor locus, as determined by biochemical studies of cultured fibroblasts.
We still need to know which tissues take up the most LDL; we need to know how much LDL is cleared by the liver and whether this clearance involves the same LDL receptor that operates in extra-hepatic cells; we need to know the mechanism for the clearance of the one-half to two-thirds of LDL that leaves the plasma by receptor-independent pathways; and finally we need to know how an abnormal accumulation of LDL in the plasma leads to the deposition of cholesterol in scavenger cells and produces atherosclerosis.
Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (i) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (ii) the recent report of linkage of the trait to the LDL receptor (chromosome 19).
To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO).
Familial hypercholesterolemia (FH) results from an inherited functional defect of the low density lipoprotein (LDL) receptor and is complicated by premature atherosclerosis.
A synergistic interaction between the apolipoprotein C-III and the LDL receptor defects produced large quantities of VLDL and LDL and enhanced the development of atherosclerosis.
Within certain families and isolated communities, the effect of a single candidate gene on atherosclerosis susceptibility may be profound, as in the case of mutations in the gene encoding the low-density lipoprotein receptor, which produce familial hypercholesterolemia and premature atherosclerosis.
We conclude that LDLR-/-; Tg(apoB+/+) mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis.
This observation could explain the higher incidence of atherosclerosis in male LDL-R deficient mice and human familial hypercholesterolemia (FH) patients.
Low-density lipoprotein receptor-related protein in atherosclerosis development: up-regulation of gene expression in patients with coronary obstruction.
Familial hypercholesterolemia (FH), a monogenic disease known to be caused by low-density lipoprotein receptor (LDLR) gene mutations, results in the development of premature atherosclerosis and coronary artery disease in affected individuals.
To investigate the effects of its structural changes on lipoprotein metabolisms and its correlation with atherosclerosis, we characterized this mutant apoE with respect to its receptor-binding, heparin-binding, and lipoprotein association.In a competitive binding assay, apoE7. dimyristoylphosphatidylcholine displayed a defective binding to the low density lipoprotein (LDL) receptor.
We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins.
Administration of antibody against CD154 to low-density lipoprotein receptor-deficient mice has been shown to reduce atherosclerosis and decrease T-lymphocyte and macrophage content; however, only initial lesions were studied.
Mutations in the low density lipoprotein (LDL)-receptor gene cause familial hypercholesterolemia (FH), an autosomal dominant disease associated to an increased risk of premature atherosclerosis.
In the present study, the human LCAT gene (hLCAT) was introduced into LDL receptor (LDLr)-deficient (Watanabe heritable hyperlipidemic) rabbits to (1) investigate the role of the LDLr pathway in the hLCAT-mediated reductions of LDL-C and (2) determine the influence of hLCAT overexpression on atherosclerosis susceptibility in an animal model of familial hypercholesterolemia.
Induction of atherosclerosis in LDL receptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta.
To determine the role of ACAT-1 in atherogenesis, we crossed the ACAT-1-/- mice with mice lacking apolipoprotein (apo) E or the low density lipoprotein receptor (LDLR), hyperlipidemic models susceptible to atherosclerosis.