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  • Title: Regulation of cholesterol synthesis by plasma lipoproteins from patients with abetalipoproteinemia.
    Author: Alam NA, Illingworth DR, Sundberg EE, Alam SS.
    Journal: Atherosclerosis; 1983 Dec; 49(3):295-305. PubMed ID: 6318779.
    Abstract:
    Despite a complete lack of apoprotein B-containing lipoproteins from the plasma of patients with abetalipoproteinemia, rates of cholesterol synthesis measured in vivo or in freshly isolated cells in vitro are not markedly elevated. These observations suggest that other lipoprotein particles present in the plasma of patients with abetalipoproteinemia may regulate cellular cholesterol synthesis in this disorder. In the present report we have studied the effects of lipoprotein fractions from plasma of normal subjects, patients with abetalipoproteinemia, and a patient with Type III hyperlipoproteinemia on cholesterol synthesis in cultured human fibroblasts. LDL from normal subjects or the HDL2 fraction from the plasma of patients with abetalipoproteinemia were effective inhibitors of cholesterol synthesis (greater than 75% inhibition at 20 micrograms protein/ml) whereas HDL3 from normal or abetalipoproteinemia plasma stimulated cholesterol synthesis. Rates of cholesterol synthesis in fibroblasts from a patient with receptor-negative homozygous familial hypercholesterolemia were only minimally reduced by prior incubation in media containing either normal LDL or HDL2 from the plasma of a patient with abetalipoproteinemia. We conclude that lipoproteins present in the HDL2 fraction of plasma from patients with abetalipoproteinemia (which are relatively rich in apoprotein E) are effective regulators of cholesterol synthesis in normal human fibroblasts and that this regulation is mediated by an interaction of these lipoproteins with the LDL (B, E) receptor. These in vitro findings may explain why rates of cholesterol synthesis are not markedly elevated in patients with abetalipoproteinemia studied in vivo.
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