Increased responsiveness to thrombin through protease-activated receptors (PAR)-1 and -4 in active Crohn's disease
| Autor: | Christian Primas, Werner Schmid, C. Gratzer, Pavol Papay, Michael Handler, Gottfried Novacek, Simon Panzer, Alexander Eser, Harald Vogelsang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty P-selectin Thrombin Platelet Adhesiveness Crohn Disease Internal medicine Platelet adhesiveness Thromboembolism medicine Humans Platelet Receptor PAR-1 Platelet activation business.industry Gastroenterology Proteolytic enzymes General Medicine Platelet Activation P-Selectin Endocrinology Coagulation Hemostasis Case-Control Studies Immunology Female Receptors Thrombin business medicine.drug |
| Zdroj: | Journal of Crohn'scolitis. 8(6) |
| ISSN: | 1876-4479 |
| Popis: | Platelets are essential in hemostasis and inflammation, thereby linking coagulation with inflammation. Abundant thrombin generation in association with inflammation is considered a major reason for the increased risk for thromboembolic events. We therefore investigated platelet responsiveness to thrombin.In this case-control study 85 patients with Crohn's disease (active CD 42, remission 43) and 30 sex- and age-matched controls were enrolled. Clinical disease activity (Harvey-Bradshaw-Index) was assessed and CD-related data were determined by chart review. Platelets' response to protease activated receptor-1 and -4 (PAR-1, -4) was assessed by whole blood platelet aggregometry (MEA), levels of platelets adhering to monocytes (PMA), and platelet surface P-selectin.Platelets' aggregation after activation with the specific PAR-1 agonist (SFLLRN) and PAR-4 agonist (AYPGKF) was higher in patients with active CD compared to patients in remission and controls (p=0.0068 and p=0.0023 for SFLLRN, p=0.0019 and 0.0003 for AYPGKF). Likewise, levels of PMA after activation with PAR-1 and PAR-4 receptor agonists were higher in patients with active CD compared to patients in remission and controls (p=0.0001 and p0.0001 for SFLLRN, p=0.0329 and p=0.0125 for AYPGKF). However, P-selectin expression on human platelets showed heterogeneous results. Only PAR-1 activation of platelets resulted in significant differences between CD patients and controls (p=0.0001 and p=0.0022 for active and inactive CD versus controls, respectively).Our data suggest a new mechanism of platelet activation which has the potential to increase risk for thromboembolism in patients with active CD which might be due to platelets poised for thrombin-inducible activation. |
| Databáze: | OpenAIRE |
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