Pravastatin reduces thrombogenicity by mechanisms beyond plasma cholesterol lowering

Laura Casani; Sonia Sanchez-Gomez; Gemma Vilahur; Lina Badimon

doi:10.1160/TH05-04-0245

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 1035-1041
DOI: 10.1160/TH05-04-0245

Platelets and Blood Cells

Schattauer GmbH

Pravastatin reduces thrombogenicity by mechanisms beyond plasma cholesterol lowering

Authors

Laura Casani

¹Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain
Sonia Sanchez-Gomez

¹Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain
Gemma Vilahur

¹Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain
Lina Badimon

¹Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain

Abstract

Summary

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely used in the management and prevention of cardiovascular disease. In addition to its major activity, plasma lipid lowering, statins have shown a wide spectrum of additional effects that may contribute to their benefits in the prevention of cardiovascular disease. Our objective was to study whether treatment with a statin, pravastatin, could reduce thrombosis triggered by damaged vessels without changing plasma cholesterol levels. A cholesterol-clamp animal model was developed by feeding swine for 100 days on an hypercholesterolemic (HL) diet; in the last 50 days, they were randomly assigned to receive either placebo (HLC) or pravastatin (5mg . kg⁻¹. day⁻¹) (HLP) in addition to the hypercholesterolemic diet. A normocholesterolemic control group (NLC) was simultaneously studied. There were no significant differences in total cholesterol, LDL and HDL plasma levels between the two groups; however, mural thrombosis triggered by both an eroded and disrupted vessel wall was significantly inhibited by pravastatin (P<0.05). Axial dependence analysis of platelet deposition revealed that pravastatin treatment reduced the increase in platelet deposition associated to the shear rate increase at the stenosis. Additionally, pravastatin treatment significantly reduced platelet membrane RhoA expression (P <0.05) and vascular wall tissue factor (TF) protein expression (P <0.05). In addition to its lipid lowering effects, pravastatin can reduce blood thrombogenicity by mechanisms independent of plasma cholesterol lowering.

Keywords

Hypercholesterolemia - statins - thrombosis - pravastatin - platelets

Full Text

References

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