New Insights into Modulation of Thrombin Formation

  • Henri M.H. Spronk
  • Julian I. Borissoff
  • Hugo ten Cate
Clinical Trials and Their Interpretations (J Plutzky, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Clinical Trials and Their Interpretations

Abstract

Thrombin is a pleiotropic enzyme that regulates hemostasis and nonhemostatic functions, including an array of actions within and on the vasculature. Physiologically, thrombin generation serves mainly to protect against thrombosis, but also to maintain vascular endothelial integrity. This protective effect is mediated in part through generation of anticoagulant enzymes, including activated protein C, formed on the action of thrombin on the endothelial receptor thrombomodulin. Partly, thrombin’s vascular effects are effectuated through interaction with protease-activated receptors on various cell types. Pathophysiologically, downregulation and shedding of anticoagulant-acting receptors such as thrombomodulin and endothelial protein C receptor may contribute to a shift in activities of thrombin towards thrombogenic and proinflammatory actions. This shift may typically occur in the process of atherosclerosis, leading to a proatherogenic direction of the effects of thrombin. Therapeutically, the long-term inhibition of thrombin may create new ways of reducing atherosclerosis burden, altering the plaque phenotype.

Keywords

Thrombin Coagulation Activated protein C Atherosclerosis Thrombosis Atherothrombosis Anticoagulant Dabigatran Vitamin K antagonist 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Henri M.H. Spronk
    • 1
  • Julian I. Borissoff
    • 2
    • 3
  • Hugo ten Cate
    • 1
  1. 1.Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute MaastrichtMaastricht UniversityMaastrichtThe Netherlands
  2. 2.Program in Cellular and Molecular MedicineBoston Children’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Immune Disease InstituteChildren’s Hospital Boston, Harvard Medical SchoolBostonUSA

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