Pleiotropic effects of the hemostatic system
Abstract
Atherothrombosis is characterized by the inflammatory process of atherosclerosis combined with a hypercoagulable state leading to superimposed thrombus formation. In atherosclerotic plaques, cell signaling can be processed by protease activated receptors (PARs), four of which have been identified thus far (PAR1-4). Proteases that are able to activate PARs can be produced systemically, but also at the site of lesions, including thrombin and Factor Xa. After PAR activation, downstream signaling can lead to both pro-inflammatory effects and a hypercoagulable state. Which specific effect occurs, depends on the type of protease and activated PAR, and site of activation. Hypercoagulable effects are mainly exerted through PAR1 and PAR4, while pro-inflammatory responses are mostly seen after PAR1 and PAR2 activation. PAR signaling pathways contribute to atherothrombosis, suggesting that inhibition of these pathways possibly prevents cardiovascular events based on this pathophysiological mechanism. In this review, we highlight the pathways by which PAR activation leads to pro-inflammatory responses and a hypercoagulable state. Furthermore, we will give an overview of potential pharmacological treatment targets that promote vascular prot...Continue Reading
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