Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1
| العنوان: | Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1 |
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| المؤلفون: | Frans A. van Nieuwenhoven, Sander Verheule, Ulrich Schotten, Arne van Hunnik, Chantal Munts, Neil A. Turner, Elisa D'Alessandro, Hugo ten Cate, Billy Scaf, Christopher J. Trevelyan, Henri M. H. Spronk |
| المساهمون: | RS: Carim - H08 Experimental atrial fibrillation, RS: Carim - B04 Clinical thrombosis and Haemostasis, Biochemie, Fysiologie, RS: Carim - Heart, Interne Geneeskunde, MUMC+: HVC Pieken Trombose (9), MUMC+: MA Alg Interne Geneeskunde (9), MUMC+: HVC Trombosezorg (8), RS: Carim - H06 Electro mechanics |
| المصدر: | Cells Cells, Vol 10, Iss 2958, p 2958 (2021) Cells, 10(11):2958. Multidisciplinary Digital Publishing Institute (MDPI) Volume 10 Issue 11 |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Gene isoform, Adult, QH301-705.5, 030204 cardiovascular system & hematology, Article, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Gene expression, Gene silencing, FIBROSIS, Animals, Humans, Receptor, PAR-1, Heart Atria, Biology (General), Rats, Wistar, Receptor, cardiac fibroblasts, Chemokine CCL2, 030304 developmental biology, Cell Proliferation, Inflammation, 0303 health sciences, Gene knockdown, Chemistry, Interleukin-6, Myocardium, Thrombin, General Medicine, Fibroblasts, PARs, Molecular biology, Up-Regulation, Protease-Activated Receptor 1, coagulation FXa, Factor Xa, HEART, Cattle |
| الوصف: | Coagulation factor (F) Xa induces proinflammatory responses through activation of protease-activated receptors (PARs). However, the effect of FXa on cardiac fibroblasts (CFs) and the contribution of PARs in FXa-induced cellular signalling in CF has not been fully characterised. To answer these questions, human and rat CFs were incubated with FXa (or TRAP-14, PAR-1 agonist). Gene expression of pro-fibrotic and proinflammatory markers was determined by qRT-PCR after 4 and 24 h. Gene silencing of F2R (PAR-1) and F2RL1 (PAR-2) was achieved using siRNA. MCP-1 protein levels were measured by ELISA of FXa-conditioned media at 24 h. Cell proliferation was assessed after 24 h of incubation with FXa ± SCH79797 (PAR-1 antagonist). In rat CFs, FXa induced upregulation of Ccl2 (MCP-1 > 30-fold at 4 h in atrial and ventricular CF) and Il6 (IL-6 ±7-fold at 4 h in ventricular CF). Increased MCP-1 protein levels were detected in FXa-conditioned media at 24 h. In human CF, FXa upregulated the gene expression of CCL2 (> 3-fold) and IL6 (> 4-fold) at 4 h. Silencing of F2R (PAR-1 gene), but not F2RL1 (PAR-2 gene), downregulated this effect. Selective activation of PAR-1 by TRAP-14 increased CCL2 and IL6 gene expression this was prevented by F2R (PAR-1 gene) knockdown. Moreover, SCH79797 decreased FXa-induced proliferation after 24 h. In conclusion, our study shows that FXa induces overexpression of proinflammatory genes in human CFs via PAR-1, which was found to be the most abundant PARs isoform in this cell type. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37d30ee8fa76dd587af0e455d14f5ad1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....37d30ee8fa76dd587af0e455d14f5ad1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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