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OBJECTIVE A semisynthetic diet with varying amounts of cholesterol was used to achieve hypercholesterolemia and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. Atherosclerotic lesions were measured as cross-sectional area at the aortic root and brachiocephalic artery and by en face analysis of aortic lesion area in 209 male and female animals on(More)
apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl(More)
Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in the formation of lesions of atherosclerosis. This localized accumulation of leukocytes is a multistep process in which the endothelium remains intact and may regulate leukocyte recruitment by expressing specific adhesion molecules. To examine the(More)
Apolipoprotein (apo) E-deficient transgenic mice develop marked hyperlipidemia and progressive atherosclerotic lesions. To explore whether oxidative modification of lipoproteins is involved in atherogenesis in this murine model, we performed extensive immunocytochemical studies. Atherosclerotic lesions ranging from early fatty streaks to very advanced(More)
BACKGROUND The pathogenesis of atherosclerosis is currently being investigated in genetically engineered small animals. Methods to follow the time course of the developing pathology and/or the responses to therapy in vivo are limited. METHODS AND RESULTS To address this problem, we developed a noninvasive MR microscopy technique to study in vivo(More)
RATIONALE The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. OBJECTIVE To determine whether there is defective efferocytosis in a mouse(More)
BACKGROUND Moderate alcohol intake is associated with lower atherosclerosis risk, presumably due to increased HDL cholesterol (HDL-C) concentrations; however, the metabolic mechanisms of this increase are poorly understood. METHODS AND RESULTS We tested the hypothesis that ethanol increases HDL-C by raising transport rates (TRs) of the major HDL(More)
UNLABELLED Background- Variation in LDL-cholesterol (LDL-C) among individuals is a complex genetic trait involving multiple genes and gene-environment interactions. METHODS AND RESULTS In a genome-wide association study (GWAS) to identify genetic variants influencing LDL-C in an isolated population from Kosrae, we observed associations for SNPs in the(More)
To study exogenous fat metabolism, we used the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). Postprandial RP concentrations were followed in total plasma, and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions. In normal subjects postprandial(More)
Electrophoretic studies of human apoE have shown that it is composed of numerous isoprotein components (1-6). The complexity of apoE results from post-trans-lational modification with carbohydrate chains containing sialic acid (7, 8) and from genetic polymorphism in the human population (3, 8-10). The early genetic models could not explain satisfactorily(More)