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Thromb Haemost 2002; 87(04): 748-755
DOI: 10.1055/s-0037-1613075
Review Article
Schattauer GmbH

Cholesterol-induced Thrombogenicity of the Vessel Wall: Inhibitory Effect of Fluvastatin

Marina Camera
1   Department of Pharmacological Sciences, University of Milan
2   Monzino Cardiologic Center IRCCS, Milan
,
Vincenzo Toschi
3   Department of Hematology and Blood Transfusion, San Carlo Borromeo Hospital, Milan, Italy
,
Carmen Comparato
1   Department of Pharmacological Sciences, University of Milan
,
Roberta Baetta
1   Department of Pharmacological Sciences, University of Milan
,
Francesca Rossi
1   Department of Pharmacological Sciences, University of Milan
,
Michele Fuortes
4   Department of Cell Biology, Weill Medical College of Cornell University, New York, NY
,
Michael D. Ezekowitz
5   Section of Cardiovascular Medicine, Yale University, New Haven, Connecticut, USA
,
Rodolfo Paoletti
1   Department of Pharmacological Sciences, University of Milan
,
Elena Tremoli
1   Department of Pharmacological Sciences, University of Milan
2   Monzino Cardiologic Center IRCCS, Milan
› Author AffiliationsGrant support: The Commission of the European Communities HIFMECH Study, Contract BMH4-CT96-0272 and Novartis S.p.A., Basel (Switzerland).
Further Information

Publication History

Received 15 October 2001

Accepted after resubmission 21 January 2002

Publication Date:
08 December 2017 (online)

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Summary

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 a 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 IκBa in unstimulated as well as in TNFa-stimulated cells and also impaired the TNF-α-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.

Keywords

Thrombosis - atherosclerosis - hypercholesterolemia - tissue factor
 

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