Effect of the new HMG-CoA reductase inhibitor cerivastatin (BAY W 6228) on migration, proliferation and cholesterol synthesis in arterial myocytes

Alberto Corsini, L. Arnaboldi, M. Raiteri, P. Quarato, A. Faggiotto, R. Paoletti, R. Fumagalli

Research output: Contribution to journalArticlepeer-review

Abstract

The major relation existing between cell growth, migration and cholesterol homeostasis prompted us to investigate the effect of the new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin (BAY W 6228) on these cellular events. The molecule inhibited in a dose-dependent manner the migration and the replication (evaluated as cell number and nuclear incorporation of 3H-thymidine) of rat arterial SMC with IC50 values of 2.7 μM and 0.5 μM, respectively. Among the tested statins BAY W 6228 resulted to be the most potent inhibitor of cholesterol synthesis and cell proliferation. Conditions producing 80-90% inhibition of cholesterol synthesis correlate with approximately 50% inhibition of cell growth. Similar results were obtained in SMC from human femoral artery. The in vitro inhibition of cell migration and proliferation induced by BAY W 6228 (80% decrease) was completely prevented by the addition of mevalonate and partially prevented (60-80%) by farnesol and geranylgeraniol, confirming the specific role of isoprenoid metabolites-probably through a prenylated protein(s)-in regulating these cellular events. The present results provide evidence that BAY W 6228 interferes, at least in vivo, with smooth muscle cells migration and proliferation, major processes involved in atherogenesis.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalPharmacological Research
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 1996

Keywords

  • BAY W 6228
  • Cerivastatin
  • Isoprenoids
  • Myocyte migration
  • Myocyte proliferation
  • Statins

ASJC Scopus subject areas

  • Pharmacology

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