Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells
Atrial fibrillation (AF), characterised by irregular high-frequency contractions of the atria of the heart, is of increasing clinical importance. The reasons are the increasing prevalence and thromboembolic complications caused by AF. So-called atrial remodelling is characterised, among other things...
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MDPI AG
2023-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/24/2849 |
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| author | Lukas Ruf Alicja Bukowska Andreas Gardemann Andreas Goette |
| author_facet | Lukas Ruf Alicja Bukowska Andreas Gardemann Andreas Goette |
| author_sort | Lukas Ruf |
| collection | DOAJ |
| description | Atrial fibrillation (AF), characterised by irregular high-frequency contractions of the atria of the heart, is of increasing clinical importance. The reasons are the increasing prevalence and thromboembolic complications caused by AF. So-called atrial remodelling is characterised, among other things, by atrial dilatation and fibrotic remodelling. As a result, AF is self-sustaining and forms a procoagulant state. But hypercoagulation not only appears to be the consequence of AF. Coagulation factors can exert influence on cells via protease-activated receptors (PAR) and thereby the procoagulation state could contribute to the development and maintenance of AF. In this work, the influence of FXa on Heart Like-1 (HL-1) cells, which are murine adult atrial cardiomyocytes (immortalized), was investigated. PAR1, PAR2, and PAR4 expression was detected. After incubations with FXa (5–50 nM; 4–24 h) or PAR1- and PAR2-agonists (20 µM; 4–24 h), no changes occurred in PAR expression or in the inflammatory signalling cascade. There were no time- or concentration-dependent changes in the phosphorylation of the MAP kinases ERK1/2 or the p65 subunit of NF-κB. In addition, there was no change in the mRNA expression of the cell adhesion molecules (ICAM-1, VCAM-1, fibronectin). Thus, FXa has no direct PAR-dependent effects on HL-1 cells. Future studies should investigate the influence of FXa on human cardiomyocytes or on other cardiac cell types like fibroblasts. |
| first_indexed | 2024-03-08T20:55:12Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T20:55:12Z |
| publishDate | 2023-12-01 |
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| spelling | doaj.art-e912484f46634998b80f9784b73be1392023-12-22T13:59:46ZengMDPI AGCells2073-44092023-12-011224284910.3390/cells12242849Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 CellsLukas Ruf0Alicja Bukowska1Andreas Gardemann2Andreas Goette3Institute of Clinical Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, GermanyInstitute of Clinical Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, GermanyInstitute of Clinical Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, GermanyInstitute of Clinical Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, GermanyAtrial fibrillation (AF), characterised by irregular high-frequency contractions of the atria of the heart, is of increasing clinical importance. The reasons are the increasing prevalence and thromboembolic complications caused by AF. So-called atrial remodelling is characterised, among other things, by atrial dilatation and fibrotic remodelling. As a result, AF is self-sustaining and forms a procoagulant state. But hypercoagulation not only appears to be the consequence of AF. Coagulation factors can exert influence on cells via protease-activated receptors (PAR) and thereby the procoagulation state could contribute to the development and maintenance of AF. In this work, the influence of FXa on Heart Like-1 (HL-1) cells, which are murine adult atrial cardiomyocytes (immortalized), was investigated. PAR1, PAR2, and PAR4 expression was detected. After incubations with FXa (5–50 nM; 4–24 h) or PAR1- and PAR2-agonists (20 µM; 4–24 h), no changes occurred in PAR expression or in the inflammatory signalling cascade. There were no time- or concentration-dependent changes in the phosphorylation of the MAP kinases ERK1/2 or the p65 subunit of NF-κB. In addition, there was no change in the mRNA expression of the cell adhesion molecules (ICAM-1, VCAM-1, fibronectin). Thus, FXa has no direct PAR-dependent effects on HL-1 cells. Future studies should investigate the influence of FXa on human cardiomyocytes or on other cardiac cell types like fibroblasts.https://www.mdpi.com/2073-4409/12/24/2849atrial fibrillationatrial remodelingatrial myocytesHL-1 cellsFXaFXa-induced signal transduction |
| spellingShingle | Lukas Ruf Alicja Bukowska Andreas Gardemann Andreas Goette Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells Cells atrial fibrillation atrial remodeling atrial myocytes HL-1 cells FXa FXa-induced signal transduction |
| title | Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells |
| title_full | Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells |
| title_fullStr | Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells |
| title_full_unstemmed | Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells |
| title_short | Coagulation Factor Xa Has No Effects on the Expression of PAR1, PAR2, and PAR4 and No Proinflammatory Effects on HL-1 Cells |
| title_sort | coagulation factor xa has no effects on the expression of par1 par2 and par4 and no proinflammatory effects on hl 1 cells |
| topic | atrial fibrillation atrial remodeling atrial myocytes HL-1 cells FXa FXa-induced signal transduction |
| url | https://www.mdpi.com/2073-4409/12/24/2849 |
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