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Thromb Haemost 2002; 87(04): 748-755
DOI: 10.1055/s-0037-1613075
DOI: 10.1055/s-0037-1613075
Review Article
Cholesterol-induced Thrombogenicity of the Vessel Wall: Inhibitory Effect of Fluvastatin
Authors
Grant 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)
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.
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