Platelet-derived miR-223 promotes a phenotypic switch in arterial injury repair

Zeng, Zhi; Xia, Luoxing; Fan, Xuejiao; Ostriker, Allison; Yarovinsky, Timur O.; Su, Meiling; Zhang, Yuan; Peng, Xiangwen; Xie, Yi; Pi, Lei; Gu, Xiaoqiong; Chung, Sookja K.; Martin, Kathleen A.; Liu, Renjing; Hwa, John; Tang, Wai Ho

doi:10.1172/jci124508

Cited by 86 publications

(66 citation statements)

References 46 publications

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“…MiR-223 is known to target P2Y 12 mRNA and lower levels may therefore convey increased resistance to P2Y 12 inhibition. Reduced expression of miR-223 in platelets has also been shown in diabetes; which is a strong risk factor for coronary artery disease and can be associated with high on-treatment platelet reactivity [34,35].…”

Section: Discussionmentioning

confidence: 94%

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Braza-Boïls

Barwari

Gutmann

et al. 2020

IJMS

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There is evidence for the effects of platelet inhibition on innate immune activation. Circulating microRNAs (miRNAs) have been implicated as markers of platelet and leukocyte activation. In the present study, we assessed the effects of P2Y 12 inhibitors on platelet and leukocyte miRNAs during endotoxemia. Healthy volunteers were randomly assigned to receive oral ticagrelor (n = 10), clopidogrel (n = 8) or no drug (n = 8) for one week, followed by an intravenous bolus of 2 ng/kg endotoxin. Serum was collected at baseline, after one week of antiplatelet treatment and 6 and 24 h after endotoxin administration. MiRNAs were screened using LNA-based qPCR, followed by TaqMan-qPCR validation of candidates. Clinical validation was performed in 41 sepsis patients. Platelet-enriched miR-197, miR-223 and miR-223* were decreased in volunteers following antiplatelet therapy. Endotoxin increased platelet miRNAs, whilst the opposite effect was seen for leukocyte-enriched miR-150. Neither of these endotoxin-mediated effects were altered by P2Y 12 inhibitors. Sepsis patients with fatal outcomes (n = 12) had reduced miR-150 levels compared with survivors (n = 29). In conclusion, we show that miR-150 is downregulated in experimental endotoxemia and can predict survival in sepsis but is unaffected by P2Y 12 inhibition. While P2Y 12 inhibition reduces platelet-associated miRNAs in healthy volunteers, it fails to attenuate the response of platelet miRNAs to endotoxemia.

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Section: Discussionmentioning

confidence: 94%

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Braza-Boïls

Barwari

Gutmann

et al. 2020

IJMS

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“…Nevertheless, Zeng and coworkers found that activated platelet internalization by VSMCs rather than MPs increased miR-223 levels promoting VSMCs differentiation. Platelets from diabetic mice had reduced miR-223 levels and consequently increased VSMCs hyperplasia [112].…”

Section: Involvement Of Platelets In Intercellular Communicationmentioning

confidence: 99%

MicroRNAs in Platelets: Should I Stay or Should I Go?

Águila¹,

Cuenca-Zamora²,

Martı́nez³

et al. 2020

Platelets

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In this chapter, we discuss different topics always using the microRNA as the guiding thread of the review. MicroRNAs, member of small noncoding RNAs family, are an important element involved in gene expression. We cover different issues such as their importance in the differentiation and maturation of megakaryocytes (megakaryopoiesis), as well as the role in platelets formation (thrombopoiesis) focusing on the described relationship between miRNA and critical myeloid lineage transcription factors such as RUNX1, chemokines receptors as CRCX4, or central hormones in platelet homeostasis like TPO, as well as its receptor (MPL) and the TPO signal transduction pathway, that is JAK/STAT. In addition to platelet biogenesis, we review the microRNA participation in platelets physiology and function. This review also introduces the use of miRNAs as biomarkers of platelet function since the detection of pathogenic situations or response to therapy using these noncoding RNAs is getting increasing interest in disease management. Finally, this chapter describes the participation of platelets in cellular interplay, since extracellular vesicles have been demonstrated to have the ability to deliver microRNAs to others cells, modulating their function through intercellular communication, redefining the extracellular vesicles from the so-called "platelet dust" to become mediators of intercellular communication.

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“…The recent report by Zeng et al builds upon an exciting area of research in the cardiovascular field: the ability of platelets to modulate the gene expression in other cells in contact with the blood by transferring (mi)RNAs, which then alters the physiology of the recipient cells. This ability to transfer RNAs was first reported in 2012, when the delivery of mRNAs in platelet‐like particles from the Meg01 cell line to human umbilical vein endothelial cells (HUVECs) and the THP‐1 monocytic cell line was described.…”

Section: Platelet Rna Transfermentioning

confidence: 99%

“…The mechanisms, cellular and molecular targets, and functional outcomes of horizontal transfer of platelet miRNAs are active areas of investigation. Most recently, Zeng et al reported a new cellular target of platelet miRNAs: vascular smooth muscle cells (VSMCs) in vitro following coincubation with platelets, and in vivo following wire injury to the femoral artery in mice, with effects on the VSMC injury response . Even more surprising is the apparent engulfment of intact platelets by VSMCs, representing not only exchange of genetic material, but exchange of complex cellular content between these vascular cells.…”

Section: Introductionmentioning

confidence: 99%

Horizontal RNA transfer goes deep: platelet consumption and microRNA utilization by vascular smooth muscle cells

Goldfinger

Edelstein

2019

Journal of Thrombosis and Haemostasis

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| INTRODUC TI ON MicroRNAs (miRNAs), which are short non-coding RNAs that repress translation of cognate sequence-matched mRNAs through multiple mechanisms, have been established as both important regulators and key biomarkers of cardiovascular function. miRNAs have been shown to modulate gene expression, resulting in altered development and/or functional responses, in every type of vascular cell. miRNAs also circulate in plasma, either complexed to lipoproteins or contained within extracellular vesicles (EVs). Circulation of miRNAs enables their functionality both as biomarkers for altered gene expression to indicate and describe pathologic conditions, and as mediators of horizontal gene transfer between vascular cells in an autocrine or a paracrine fashion. miRNAs are well suited to these roles, owing to their relatively long half-life (approximately 5 days), which can support long-term gene regulation in distal cells. Horizontal transfer of intercellular RNA extends the reach of miR-NAs beyond their cell of origin, and adds new dimensions to gene regulation in vivo. Horizontal miRNA transfer may be of particular relevance in postmitotic and senescent vascular cells, in which modulation of gene expression by miRNAs can affect cellular activation in acute or chronic settings. In particular, platelets are highly enriched in miRNAs, and platelets are emerging as major sources and transfer hubs mediating miRNA exchange in blood. Platelet-derived microvesicles (PMVs) constitute a major proportion of plasma microvesicles (MVs), and these structures have been shown to deliver platelet miR-NAs to other vascular and extravascular cells in multiple contexts. Moreover, phagocytosis of intact platelets has been demonstrated in several vascular cell types, including endothelial cells, neutrophils, and monocytes, providing yet another opportunity for miRNA exchange by engulfment of whole platelets. The mechanisms, cellular and molecular targets, and functional outcomes of horizontal transfer of platelet miRNAs are active areas of investigation. Most recently, Zeng et al reported a new cellular target of platelet miR-NAs: vascular smooth muscle cells (VSMCs) in vitro following coincubation with platelets, and in vivo following wire injury to the femoral artery in mice, with effects on the VSMC injury response. 1Even more surprising is the apparent engulfment of intact platelets by VSMCs, representing not only exchange of genetic material, but exchange of complex cellular content between these vascular cells.In this Neighborhood Watch, we discuss the background, implications, unanswered questions, and future perspectives of this study. | PL ATELE T RNA TR AN S FERThe recent report by Zeng et al 1 builds upon an exciting area of research in the cardiovascular field: the ability of platelets to modulate the gene expression in other cells in contact with the blood by transferring (mi)RNAs, which then alters the physiology of the recipient cells. This ability to transfer RNAs was first reported in 2012, when the delivery of mRNAs ...

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Platelet-derived miR-223 promotes a phenotypic switch in arterial injury repair

Cited by 86 publications

References 46 publications

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

MicroRNAs in Platelets: Should I Stay or Should I Go?

Horizontal RNA transfer goes deep: platelet consumption and microRNA utilization by vascular smooth muscle cells

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