Vol. 41, No. 1, Jonuary 1997
BIOCHEMISTRY and MOLECULAR BIOLOGY INTERNATIONAL Pages 33-39
REGULATION OF C H O L E S T E R O L SYNTHESIS AND ESTERIFICATION IN PRIMARY CULTURES OF MACROPHAGES F O L L O W I N G UPTAKE OF CHYLOMICRON REMNANTS Kenneth C.-W. Yu and John C.L. Mamo Departments of Physiology and Medicine, University of Western Australia, Nedlands 6907, Australia Received August 14, 1996 Received after revisionNovember8 1996 Summary The effects of chylomicron remnants (CR), 13-very-low-density-lipoproteins (13-VLDL) and low-density-lipoproteins (LDL) on intracellular cholesterol synthesis and esterification in primary rabbit macrophages was determined by assaying for HMG-CoA reductase activity and cholesterol esterification. At physiological cholesterol concentrations, both CR and LDL inhibited cholesterol synthesis by almost 60% while 13-VLDL was less potent achieving only 30% inhibition. Cholesterol esterification rates were increased four-fold by CR and LDL, whereas 13-VLDL increased esterification 14 times above controls. Qualitatively, the effect of CR on cholesterol synthesis and esterification in rabbit macrophages differs from observations in transformed macrophage cells. Quantitatively, the enhanced rates of cholesterol esterification and weak inhibition of cholesterol synthesis following 13-VLDL uptake may explain why this lipoprotein rapidly induces foam cell formation in vitro. Keywords: chylomicron remnants, low-density-lipoproteins, 13-very-low-density-lipoproteins, cholesterol synthesis, cholesterol esterification, macrophages Introduction Lipid-laden macrophages are commonly known as foam cells and are a hallmark feature of early atherosclerotic lesions (1). Arterial foam cells are derived from circulating monocytes as a consequence o f an inflammatory response, possibly caused by the extracellular Abbreviations used: ACAT: acyl cholesterol acyltransferase, CR: chylomicron remnants, HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A, LDL: low-density-lipoproteins, 13VLDL: 13-very-low-density-lipoproteins, NZW: New Zealand White, Address for correspondence: Dr. John Mamo University Department of Medicine, University of Western Australia, Box X2213, GPO Perth, Australia Tel: 61-9-2240263 Fax: 61-9-2240246
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