Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture

Jürgen R. Sindermann, Li Fan, Kirsten A. Weigel, David Troyer, Joachim G. Müller, Annette Schmidt, Keith L. March, Günter Breithardt

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

We investigated the influence of lovastatin, simvastatin and pravastatin on proliferation and viability of vascular smooth muscle cells (SMC) in vitro and studied the effects of lovastatin on a mouse SMC line transgenic for a temperature-sensitive mutant of SV40 large T antigen (TAg), known to inhibit the function of p53 and pRb family members. We found that lovastatin and simvastatin inhibited cell proliferation by provoking G0/G1 phase arrest with concomitant depression of the proliferation antigen Ki-67/MIB-1. Lovastatin at high concentrations of 20 μmol/l caused cell death in the presence of serum but not under serum starved conditions, which was verified on the basis of increased DNA strand breaks, decreased DNA content and morphological alterations seen by electron microscopy. Cell death was also found for simvastatin, whereas pravastatin did not exhibit antiproliferative or cytotoxic effects. Mouse SMC transgenic for TAg did not show any impaired sensitivity to the antiproliferative and cell death inducing effect of lovastatin, but both effects could be antagonized by the supplementation of mevalonate. The data indicate that antiproliferative and cytotoxic effects of lovastatin are caused by the using up of products of mevalonate metabolism and do not require the presence of p53 or pRb. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)331-341
Number of pages11
JournalAtherosclerosis
Volume150
Issue number2
DOIs
StatePublished - Jun 2000

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lovastatin
Smooth Muscle Myocytes
Cell Culture Techniques
Simvastatin
Pravastatin
Mevalonic Acid
Cell Death
Viral Tumor Antigens
Ki-67 Antigen
Polyomavirus Transforming Antigens
Cell Cycle Resting Phase
DNA Breaks
G1 Phase
Serum
Vascular Smooth Muscle
Electron Microscopy
Cell Proliferation
Cell Line
Temperature

Keywords

  • Cell death
  • p53
  • Proliferation
  • Smooth muscle cells
  • SV40 large TAg

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Sindermann, J. R., Fan, L., Weigel, K. A., Troyer, D., Müller, J. G., Schmidt, A., ... Breithardt, G. (2000). Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture. Atherosclerosis, 150(2), 331-341. https://doi.org/10.1016/S0021-9150(99)00393-7

Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture. / Sindermann, Jürgen R.; Fan, Li; Weigel, Kirsten A.; Troyer, David; Müller, Joachim G.; Schmidt, Annette; March, Keith L.; Breithardt, Günter.

In: Atherosclerosis, Vol. 150, No. 2, 06.2000, p. 331-341.

Research output: Contribution to journalArticle

Sindermann, JR, Fan, L, Weigel, KA, Troyer, D, Müller, JG, Schmidt, A, March, KL & Breithardt, G 2000, 'Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture', Atherosclerosis, vol. 150, no. 2, pp. 331-341. https://doi.org/10.1016/S0021-9150(99)00393-7
Sindermann, Jürgen R. ; Fan, Li ; Weigel, Kirsten A. ; Troyer, David ; Müller, Joachim G. ; Schmidt, Annette ; March, Keith L. ; Breithardt, Günter. / Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture. In: Atherosclerosis. 2000 ; Vol. 150, No. 2. pp. 331-341.
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