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Updated: Oct 8, 2026

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
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Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

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Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary

A Skaletz-Rorowski1, J G Müller, A Kroke

  • 1Institute for Arteriosclerosis Research, University of Münster, Germany. skaletz@uni-muenster.de

European Journal of Cell Biology
|April 27, 2001
PubMed

Insights

Lovastatin inhibits basic fibroblast growth factor (bFGF)-induced coronary smooth muscle cell proliferation by affecting protein phosphatases. This effect is reversed by mevalonate, suggesting a role in signal transduction pathways.

Area of Science:

  • Cardiovascular Biology
  • Cell Signaling
  • Pharmacology

Background:

  • Mitogen-activated protein kinase (MAPK) activation via protein kinase C (PKC) isoforms is crucial for basic fibroblast growth factor (bFGF)-induced coronary smooth muscle cell (cSMC) proliferation.
  • Understanding the impact of cholesterol-lowering drugs on these signaling pathways is important for cardiovascular health.

Purpose of the Study:

  • To investigate the effects of lovastatin, an HMG CoA reductase inhibitor, on bFGF-induced signal transduction in cSMC.
  • To elucidate the specific mechanisms by which lovastatin influences cSMC proliferation.

Main Methods:

  • Treatment of cSMC with lovastatin and bFGF.
  • Assessment of DNA synthesis, MAPK phosphorylation, Ras farnesylation, and PKC activity.
  • Analysis of protein phosphatase 1 (PP-1) and 2A (PP-2A) expression and activity.
  • Reversal studies using mevalonate and geranylgeranyl-pyrophosphate.

Main Results:

  • Lovastatin inhibited bFGF-stimulated DNA synthesis in cSMC, an effect reversed by mevalonate and geranylgeranyl-pyrophosphate.
  • Lovastatin partially reduced bFGF-stimulated MAPK phosphorylation despite preventing Ras farnesylation.
  • Lovastatin treatment led to sustained MAPK phosphorylation and a dose-dependent increase in PKC activity, which was mevalonate-reversible.
  • Lovastatin inhibited PP-1 protein expression and suggested an impact on PP-1/PP-2A activity.

Conclusions:

  • Lovastatin inhibits bFGF-induced cSMC proliferation, potentially by interfering with dephosphorylation processes mediated by PP-1/PP-2A.
  • The findings suggest lovastatin affects PKC and MAPK signaling pathways involved in bFGF-induced mitogenesis.
  • These results highlight a novel mechanism of action for statins in vascular smooth muscle cells.

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