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-kappaB activation in the aortic arch. A consistent vessel wall platelet deposition was also observed. Treatment with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-kappaB activation, and platelet deposition (-56%). In vitro studies showed that the drug upregulated IkappaB alpha in unstimulated as well as in TNFalpha-stimulated cells and also impaired the TNFalpha-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.
Cholesterol-induced thrombogenicity of the vessel wall: inhibitory effect of fluvastatin / M. Camera, V. Toschi, C. Comparato, R. Baetta, F. Rossi, M. Fuortes, M. D. Ezekowitz, R. Paoletti, E. Tremoli. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - 87:4(2002 Apr), pp. 748-755.
|Titolo:||Cholesterol-induced thrombogenicity of the vessel wall: inhibitory effect of fluvastatin|
CAMERA, MARINA (Primo)
PAOLETTI, RODOLFO (Penultimo)
TREMOLI, ELENA (Ultimo)
|Parole Chiave:||Animals; NF-kappa B; Fatty Acids, Monounsaturated; Thrombophilia; Transcription, Genetic; Protein Prenylation; Indoles; Platelet Adhesiveness; Thromboplastin; Gene Expression Regulation; cdc42 GTP-Binding Protein; Hypercholesterolemia; Male; Signal Transduction; Hemorheology; Tumor Necrosis Factor-alpha; Anticoagulants; Aorta; Protein Processing, Post-Translational; Rabbits; Cholesterol; Anticholesteremic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Endothelium, Vascular; Enoxaparin; RNA, Messenger; Diet, Atherogenic; Cells, Cultured; I-kappa B Proteins; Umbilical Veins|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||apr-2002|
|Appare nelle tipologie:||01 - Articolo su periodico|