Antithrombotic properties of pravastatin reducing intra-thrombus fibrin deposition under high shear blood flow conditions

Masaaki Hamada; Mitsuhiko Sugimoto; Hideto Matsui; Tomohiro Mizuno; Yasuaki Shida; Masaaki Doi; Hidetada Fukushima; Kenji Nishio; Akira Yoshioka; Midori Shima

doi:10.1160/TH10-09-0587

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(02): 313-320
DOI: 10.1160/TH10-09-0587

Platelets and Blood Cells

Schattauer GmbH

Antithrombotic properties of pravastatin reducing intra-thrombus fibrin deposition under high shear blood flow conditions

Masaaki Hamada

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

,

Mitsuhiko Sugimoto

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

,

Hideto Matsui

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

,

Tomohiro Mizuno

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

,

Yasuaki Shida

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

,

Masaaki Doi

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

,

Hidetada Fukushima

²Department of Emergency and Critical Care Medicine, Nara Medical University, Kashihara, Nara, Japan

,

Kenji Nishio

²Department of Emergency and Critical Care Medicine, Nara Medical University, Kashihara, Nara, Japan

,

Akira Yoshioka

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

,

Midori Shima

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

› Author Affiliations

Abstract

Summary

In addition to lowering cholesterol, the 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have a range of pleiotropic effects that help reduce the risk of adverse cardiovascular events. We sought to understand the molecular mechanisms by which statins could exert anti-platelet actions under physiologic whole blood flow conditions. Using an in vitroperfusion chamber system, we examined the anti-platelet effects of pravastatin under whole blood flow conditions with high or low shear rates. We determined that pravastatin significantly suppressed platelet activation-dependent procoagulant activity, decreasing P-selectin membrane expression, tissue factor accumulation, and thrombin binding within platelet thrombi generated on a von Willebrand factor-surface under high shear rate conditions. These effects resulted in reductions of intra-thrombus fibrin deposition. These antithrombotic properties of pravastatin, which were comparable to those of atorvastatin, could be abrogated by mevalonate. Our experimental approach revealed a novel mechanism mediating the anti-platelet action of statins. Shear rate-dependent antithrombotic activity may explain the favourable effect of pravastatin on the reduction in cardiovascular events that typically occur in vivounder whole blood flow conditions with high shear rates.

Keywords

Statins - high fluid shear - thrombus - von Willebrand factor - fibrinogen/fibrin

Full Text

References

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