Role of RXR beta in platelet function and arterial thrombosis

Luesebrink, Enzo; Warm, Verena; Pircher, Joachim; Ehrlich, Andreas; Zhang, Zhe; Strecker, Jan; Chambon, Pierre; Massberg, Steffen; Schulz, Christian und Petzold, Tobias (2019): Role of RXR beta in platelet function and arterial thrombosis. In: Journal of Thrombosis and Haemostasis, Bd. 17, Nr. 9: S. 1489-1499

Abstract

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 RXR beta as the dominant RXR receptor in mouse platelets, prompting us to generate a megakaryocyte and platelet-specific PF4(Cre);RXR beta(flox/flox) mouse. Second, we studied activation, spreading, and aggregation of platelets from C57Bl/6 wild-type mice (WT), PF4(Cre+);RXR beta(flox/flox) mice, and PF4(Cre-);RXR beta(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 RXR beta-deficient platelets and MKs and are thus independent of RXR beta. 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 RXR beta in platelets. Conclusions Absence of the most abundant RXR receptor in mouse platelets, RXR beta, does not affect platelet function in vitro and thrombus formation in vivo. Furthermore, RXR agonists' mediated effects on platelet function are independent of RXR beta expression. Hence, our data do not support a significant contribution of RXR beta to arterial thrombosis in mice.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1538-7933
• Sprache: Englisch