PMID: 9434135Jan 20, 1998Paper

Increased cellular triglyceride levels in human monocytic and rat smooth muscle cells after lovastatin

Biochimica Et Biophysica Acta
N HrbotickyP C Weber

Abstract

Beta-hydroxy-beta-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce plasma LDL cholesterol by upregulating hepatic LDL receptors. However, their effects on lipid metabolism in extrahepatic cells may also contribute to their therapeutic benefit. We examined the effects of lovastatin (LOV) on cellular lipid levels in the human monocytic Mono Mac 6sr and cultured rat smooth muscle cells. In both cell types, LOV produced a dose-dependent increase in cellular triglycerides. This increase was observed in cells grown in the absence of exogenous lipids in the culture medium, but was more pronounced after additions of oleic acid (50 to 200 microM) and VLDL (50 to 200 microg ml-1). In Mono Mac 6sr cells grown in medium containing 10% delipidated FCS for the last 16 h, the LOV-induced rise in triglyceride levels was completely reversed by 2 mM mevalonic acid and was associated with a decrease in cellular cholesterol. However, when cells were maintained in lipoprotein-replete medium, the LOV-induced rise in triglycerides did not correlate with cellular cholesterol. LOV also reduced cellular cholesterol esterification and increased the synthesis of fatty acids and their incorporation into triglycerides and phospholipids. Incr...Continue Reading

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