Effects of lovastatin on the levels, structure, and atherogenicity of VLDL in patients with moderate hypertriglyceridemia

Sandra H. Gianturco, William A. Bradley, Shuichi Nozaki, Gloria L Vega, Scott M Grundy

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The purpose of this study was to determine whether lovastatin treatment reduced very low density lipoprotein (VLDL) abnormalities in hypertriglyceridemic subjects. Lovastatin reduced plasma triglyceride levels and the levels of total VLDL, intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol. The numbers of VLDL particles of S(f) 100-400 and S(f) 60-100 but not S(f) 20-60 particles were reduced by lovastatin, as was the amount of cholesteryl ester per particle. All VLDL subspecies bound to the LDL receptor of cultured human fibroblasts with similar, high affinities on both placebo and lovastatin, but VLDL S(f) 100- 400 and VLDL S(f) 60-100 caused less suppression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase activity after lovastatin therapy, indicating reduced LDL receptor-mediated cholesterol delivery. The average decrease in reductase suppression by VLDL S(f) 100-400 after lovastatin was 32%, similar to the 34% average decrease in cholesteryl ester content of VLDL S(f) 100- 400 after lovastatin. Although statistical significance was not achieved, there was a trend toward decreased VLDL S(f) 100-400-induced rapid, receptor- mediated triglyceride accumulation in P388D1 macrophages after lovastatin. Taken together, these observations suggest that lovastatin may be of potential benefit in decreasing the atherosclerotic complications of hypertriglyceridemia.

Original languageEnglish (US)
Pages (from-to)472-481
Number of pages10
JournalArteriosclerosis and Thrombosis
Volume13
Issue number4
DOIs
StatePublished - 1993

Keywords

  • LDL receptor
  • VLDL
  • atherosclerosis
  • foam cells
  • hypertriglyceridemia
  • lovastatin
  • triglyceride-rich lipoproteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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