title: Is thrombin a key player in the 'coagulation-atherogenesis' maze?
abstract: In addition to its established roles in the haemostatic system, thrombin is an intriguing coagulation protease demonstrating an array of effects on endothelial cells, vascular smooth muscle cells (VSMC), monocytes, and platelets, all of which are involved in the pathophysiology of atherosclerosis. There is mounting evidence that thrombin acts as a powerful modulator of many processes like regulation of vascular tone, permeability, migration and proliferation of VSMC, recruitment of monocytes into the atherosclerotic lesions, induction of diverse pro-inflammatory markers, and all of these are related to the progression of cardiovascular disease. Recent studies in transgenic mice models indicate that the deletion of the natural thrombin inhibitor heparin cofactor II promotes an accelerated atherogenic state. Moreover, the reduction of thrombin activity levels in apolipoprotein E-deficient mice, because of the administration of the direct thrombin inhibitor melagatran, attenuates plaque progression and promotes stability in advanced atherosclerotic lesions. The combined evidence points to thrombin as a pivotal contributor to vascular pathophysiology. Considering the clinical development of selective anticoagulants including direct thrombin inhibitors, it is a relevant moment to review the different thrombin-induced mechanisms that contribute to the initiation, formation, progression, and destabilization of atherosclerotic plaques.
authors.affiliation: Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center+ (MUMC+), Maastricht, The Netherlands.
authors.forename: Julian Ilcheff
authors.initials: JI
authors.lastname: Borissoff
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D013917:Thrombin / Q000502:physiology*
chemical_list: D013917:Thrombin