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

Biochim Biophys Acta. 1997 Nov 30;1349(3):211-21. doi: 10.1016/s0005-2760(97)00136-7.


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. Increased triglyceride levels were also seen in Mono Mac 6sr cells treated with the lanosterol demethylase inhibitor RS-21607 and the acylcoenzyme A:cholesterol acyltransferase inhibitor SaH 58035. Our findings suggest that the LOV-induced triglyceride accumulation involves changes in intracellular cholesterol pools regulating cellular fatty acid concentrations. Although decreased cholesterol levels in cells participating in plaque formation are beneficial, the impact of the herein described shift in intracellular neutral lipid metabolism on other cellular functions warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism
  • Amides / pharmacology*
  • Aniline Compounds / pharmacology
  • Animals
  • Anticholesteremic Agents / pharmacology
  • Cell Line
  • Cholesterol / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lipid Metabolism
  • Lipoproteins, LDL / metabolism
  • Lipoproteins, LDL / pharmacology
  • Lipoproteins, VLDL / metabolism
  • Lipoproteins, VLDL / pharmacology
  • Lovastatin / pharmacology*
  • Mevalonic Acid / pharmacology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Oleic Acid / metabolism
  • Organosilicon Compounds / pharmacology*
  • Rats
  • Rats, Wistar
  • Sulfides / pharmacology
  • Triglycerides / metabolism*


  • Acetates
  • Amides
  • Aniline Compounds
  • Anticholesteremic Agents
  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • Lipoproteins, VLDL
  • Organosilicon Compounds
  • Sulfides
  • Triglycerides
  • azalanstat
  • Oleic Acid
  • SAN 58035
  • Cholesterol
  • Lovastatin
  • Mevalonic Acid