Retinoic acid receptor‐α regulates synthetic events in human platelets

Schwertz, Hansjörg; Rowley, Jesse W.; Zimmerman, Guy A.; Weyrich, Andrew S.; Rondina, Matthew T.

doi:10.1111/jth.13861

Cited by 19 publications

(15 citation statements)

References 52 publications

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“…We appreciate the comments from de la Salle et al . regarding our recent findings on all‐ trans ‐retinoic acid as a translational control mechanism in human platelets . We agree with the notion that, when platelet molecular biology studies are performed, highly purified platelet preparations are needed.…”

supporting

confidence: 88%

“…We agree with the notion that, when platelet molecular biology studies are performed, highly purified platelet preparations are needed. As described in this report and others , we utilized a rigorous and validated method in the field of purifying platelets from whole blood . In this method, leukocyte‐immunodepleted suspensions are prepared with anti‐CD45 magnetic beads.…”

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confidence: 99%

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Retinoic acid receptor‐α regulates synthetic events in human platelets: reply

Schwertz

Rondina

2018

Journal of Thrombosis and Haemostasis

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To cite this article: Schwertz H, Rondina MT. Retinoic acid receptor-a regulates synthetic events in human platelets: reply. J Thromb Haemost 2018; 16: 1015-6. See also Schwertz H, Rowley JW, Zimmerman GA, Weyrich AS, Rondina MT. Retinoic acid receptor-a regulates synthetic events in human platelets. J Thromb Haemost 2017; 15: 2408-18 and Retinoic acid receptor-a regulates synthetic events in human platelets: comment. This issue, pp 1013-4. Addendum H. Schwertz and M. Rondina wrote the letter and gave final approval of the version to be submitted.

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supporting

confidence: 88%

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confidence: 99%

Retinoic acid receptor‐α regulates synthetic events in human platelets: reply

Schwertz

Rondina

2018

Journal of Thrombosis and Haemostasis

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“…Rondina et al described that treatment with all‐trans retinoic acid, which is structurally similar to 9cRA, disrupts the RARα‐Arp2/3 interaction and yields an inhibition of both cytoskeletal rearrangements and platelet spreading. Further, Schwertz et al showed that platelets treated with atRA have altered levels of protein synthesis compared to controls indicating effects on protein regulation. Taking this into account, it seems reasonable that molecules acting as RXR agonists may also affect platelet function through other NRs.…”

Section: Discussionmentioning

confidence: 99%

Role of RXRβ in platelet function and arterial thrombosis

Lüsebrink

Warm

Pircher

et al. 2019

Journal of Thrombosis and Haemostasis

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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 RXRβ as the dominant RXR receptor in mouse platelets, prompting us to generate a megakaryocyte and platelet-specific PF4 Cre ;RXRβ flox/flox mouse. Second, we studied activation, spreading, and aggregation of platelets from C57Bl/6 wild-type mice (WT), PF4 Cre+ ;RXRβ flox/flox mice, and PF4 Cre-;RXRβ 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 RXRβ-deficient platelets and MKs and are thus independent of RXRβ. 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 RXRβ in platelets. Conclusions: Absence of the most abundant RXR receptor in mouse platelets, RXRβ, does not affect platelet function in vitro and thrombus formation in vivo. Furthermore, RXR agonists' mediated effects on platelet function are independent of RXRβ expression. Hence, our data do not support a significant contribution of RXRβ to arterial thrombosis in mice. K E Y W O R D S nuclear receptor, platelet function, retinoids, RXR, thrombosis S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Lüsebrink E, Warm V, Pircher J, et al. Role of RXRβ in platelet function and arterial thrombosis. J

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“… 41 Recent developments have reported that RARα is capable of regulating protein synthesis (including microtubule-associated protein-1 light chain 3 beta 2) in human platelets by binding to a subset of mRNAs and blocking translation. Schwertz et al 66 found that platelets treated with RARα ligand atRA for several hours displayed significantly altered levels of protein synthesis compared to controls.…”

Section: Type II Nrsmentioning

confidence: 99%

Non-genomic effects of nuclear receptors: insights from the anucleate platelet

Unsworth¹,

Flora²,

Gibbins³

2018

Cardiovascular Research

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Nuclear receptors (NRs) have the ability to elicit two different kinds of responses, genomic and non-genomic. Although genomic responses control gene expression by influencing the rate of transcription, non-genomic effects occur rapidly and independently of transcriptional regulation. Due to their anucleate nature and mechanistically well-characterized and rapid responses, platelets provide a model system for the study of any non-genomic effects of the NRs. Several NRs have been found to be present in human platelets, and multiple NR agonists have been shown to elicit anti-platelet effects by a variety of mechanisms. The non-genomic functions of NRs vary, including the regulation of kinase and phosphatase activity, ion channel function, intracellular calcium levels, and production of second messengers. Recently, the characterization of mechanisms and identification of novel binding partners of NRs have further strengthened the prospects of developing their ligands into potential therapeutics that offer cardio-protective properties in addition to their other defined genomic effects.

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Retinoic acid receptor‐α regulates synthetic events in human platelets

Cited by 19 publications

References 52 publications

Retinoic acid receptor‐α regulates synthetic events in human platelets: reply

Retinoic acid receptor‐α regulates synthetic events in human platelets: reply

Role of RXRβ in platelet function and arterial thrombosis

Non-genomic effects of nuclear receptors: insights from the anucleate platelet

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