Role of RXRβ in platelet function and arterial thrombosis
| Autor: | Joachim Pircher, Enzo Lüsebrink, Steffen Massberg, Verena Warm, Pierre Chambon, Christian Schulz, Andreas Ehrlich, Zhe Zhang, Tobias Petzold, Jan Strecker |
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| Přispěvatelé: | Klinikum der Universitat Munchen, Ludwig-Maximilians-Universität München (LMU), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), univOAK, Archive ouverte |
| Rok vydání: | 2019 |
| Předmět: |
Blood Platelets
Male retinoids platelet function RXR [SDV.GEN] Life Sciences [q-bio]/Genetics 030204 cardiovascular system & hematology Retinoid X receptor Ferric Compounds Thrombopoiesis Mice 03 medical and health sciences 0302 clinical medicine Chlorides Megakaryocyte In vivo medicine Animals nuclear receptor Platelet Carotid Artery Thrombosis Platelet activation Receptor thrombosis Mice Knockout [SDV.GEN]Life Sciences [q-bio]/Genetics Chemistry Hematology Platelet Activation Cell biology DNA-Binding Proteins Mice Inbred C57BL medicine.anatomical_structure Nuclear receptor Knockout mouse Female |
| Zdroj: | Journal of Thrombosis and Haemostasis Journal of Thrombosis and Haemostasis, 2019, 17 (9), pp.1489-1499. ⟨10.1111/jth.14531⟩ |
| ISSN: | 1538-7836 |
| Popis: | OBJECTIVE: Retinoid X receptors (RXR) are a family of nuclear receptors that play critical roles in the regulation of numerous fundamental biological processes including cell proliferation, differentiation, and death. Earlier studies suggested that treatment with RXR agonists attenuates platelet activation in all adults (male and femal) and mice; however, the underlying molecular mechanisms have remained insufficiently understood. To elaborate further on this issue, we characterized megakaryocyte and platelet-specific RXR knockout mice to study platelet function in vitro and arterial thrombosis in vivo. APPROACH AND RESULTS: First, we identified RXRbeta as the dominant RXR receptor in mouse platelets, prompting us to generate a megakaryocyte and platelet-specific PF4(Cre) ;RXRbeta(flox/flox) mouse. Second, we studied activation, spreading, and aggregation of platelets from C57Bl/6 wild-type mice (WT), PF4(Cre+) ;RXRbeta(flox/flox) mice, and PF4(Cre-) ;RXRbeta(flox/flox) littermate controls in the presence or absence of RXR ligands, that is, 9-cis-retinoic acid (9cRA) and methoprene acid (MA). We found that in vitro treatment with RXR ligands attenuates spreading and aggregation of platelets and increases proplatelet particle formation from megakaryocytes (MK). However, these effects are also observed in RXRbeta-deficient platelets and MKs and are thus independent of RXRbeta. Third, we investigated arterial thrombus formation in an iron chloride (FeCl3)-induced vascular injury model in vivo, which is also not affected by the absence of RXRbeta in platelets. CONCLUSIONS: Absence of the most abundant RXR receptor in mouse platelets, RXRbeta, does not affect platelet function in vitro and thrombus formation in vivo. Furthermore, RXR agonists' mediated effects on platelet function are independent of RXRbeta expression. Hence, our data do not support a significant contribution of RXRbeta to arterial thrombosis in mice. |
| Databáze: | OpenAIRE |
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