Cholesterol-induced thrombogenicity of the vessel wall: Inhibitory effect of fluvastatin

Marina Camera, Vincenzo Toschi, Carmen Comparato, Roberta Baetta, Francesca Rossi, Michele Fuortes, Michael D. Ezekowitz, Rodolfo Paoletti, Elena Tremoli

Research output: Contribution to journalArticlepeer-review

Abstract

High cholesterol levels are a known risk factor for coronary events. The molecular links between high serum cholesterol and the increased thrombogenicity of the arterial wall are still matter of investigation. In the present study we investigate the relationship between plasma cholesterol, thrombus formation and TF expression in atherosclerotic rabbit model. Hypercholesterolemic rabbits showed a pronounced TF staining as well as NF-κB activation in the aortic arch. A consistent vessel wall platelet deposition was also observed. Treatment with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-κB activation, and platelet deposition (-56%). In vitro studies showed that the drug upregulated IκBα in unstimulated as well as in TNFα-stimulated cells and also impaired the TNFα-induced Cdc42 prenylation, indicating that fluvastatin interferes with the transcriptional activation of TF gene. These results indicate that the prothrombotic phenotype of arterial wall, associated with elevated serum cholesterol levels, is mediated by TF overexpression. Fluvastatin treatment reduces the prothrombotic tendency by inhibiting TF synthesis.

Original languageEnglish
Pages (from-to)748-755
Number of pages8
JournalThrombosis and Haemostasis
Volume87
Issue number4
Publication statusPublished - 2002

Keywords

  • Atherosclerosis
  • Hypercholesterolemia
  • Thrombosis
  • Tissue factor

ASJC Scopus subject areas

  • Hematology

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