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Lipoprotein Size and Susceptibility to Atherosclerosis — Insights from Genetically Modified Mouse Models

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High plasma levels of the apo-B-containing lipoproteins are casually implicated in the pathogenesis of atherosclerosis. This finding, backed by decades of animal and human studies, has sparked interest in defining which classes of apo-B-containing lipoprotein particles are most atherogenic. Although small LDL particles and larger remnant lipoproteins both appear to be atherogenic, it has been difficult to discern which particles are the most atherogenic. Here, we summarize several mouse models that have provided insights into this issue. The influence of lipoprotein size on susceptibility to atherosclerosis was examined by studying the phenotypes of two strains of mice with virtually identical levels of plasma cholesterol—Ldlr-/-Apob100/100 and Apoe-/-Apob100/100 mice. The Ldlr-/-Apob100/100 mice, where the cholesterol is in small LDL particles, had far more atherosclerosis than Apoe-/-Apob100/100 mice, where virtually all of the cholesterol was in larger, VLDL-sized particles. Another intriguing animal model is the Gpihbp1-deficient mouse. GPIHBP1 is an endothelial cell platform for lipolysis, and mice lacking this protein have an accumulation of large, triglyceride-rich lipoproteins. Defining the extent of atherosclerosis in these mice should provide new insights into the atherogenicity of large, triglyceride-rich lipoproteins.

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Document Type: Research Article

Publication date: 2008-03-01

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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