Association of MicroRNAs and YRNAs With Platelet Function.
Association of MicroRNAs and YRNAs With Platelet Function.
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DOI：
10.1161/circresaha.114.305663
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发表时间：
2016-02-05
影响因子：
20.1
通讯作者：
Mayr M
中科院分区：
文献类型：
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作者：
Kaudewitz D;Skroblin P;Bender LH;Barwari T;Willeit P;Pechlaner R;Sunderland NP;Willeit K;Morton AC;Armstrong PC;Chan MV;Lu R;Yin X;Gracio F;Dudek K;Langley SR;Zampetaki A;de Rinaldis E;Ye S;Warner TD;Saxena A;Kiechl S;Storey RF;Mayr M
质粒化的microRNA（miRNAs）。血浆miRNA在血小板抑制后发生变化。目前尚不清楚血浆miRNA水平是否与血小板功能相关。将小RNA与血小板反应性联系起来。血浆中小RNA的下一代测序揭示了分别对应于miRNA和YRNA的22-23和32-33个核苷酸处的两个峰。在YRNA中，主要检测到RNY 4和RNY 5片段。在125名有ACS病史的患者中测量了血浆miRNA和YRNA，这些患者在急性事件发生后30天进行了血小板功能的详细评估。使用定量实时聚合酶链反应，在ACS患者中评估了92种miRNAs，这些患者接受了不同的抗血小板治疗。关键的血小板相关miRNAs和YRNAs与血小板功能测试相关。miR-223（rp=0.28，n=121，P=0.002）、miR-126（rp=0.22，n=121，P=0.016）等血小板miRNAs和YRNAs与血管舒张剂刺激的磷蛋白磷酸化检测呈显著正相关。YRNA、miR-126和miR-223也是显示对血小板依赖性最大的小RNA，并且在基于人群的Bruneck研究中与P-选择素、血小板因子4和血小板碱性蛋白的血浆水平密切相关（n=669）。促进pri-miR-126加工为成熟miR-126的单核苷酸多态性导致循环血小板活化标志物的升高。在小鼠中抑制miR-126可降低血小板聚集。miR-126直接或间接影响ADAM 9和P2 Y12受体的表达。血小板相关的血浆miRNAs和YRNAs水平与ACS患者的血小板功能测试和一般人群的血小板活化标志物相关。miR-126的改变影响血小板反应性。
Platelets shed microRNAs (miRNAs). Plasma miRNAs change upon platelet inhibition. It is unclear if plasma miRNA levels correlate with platelet function. To link small RNAs to platelet reactivity. Next-generation sequencing of small RNAs in plasma revealed two peaks at 22-23 and 32-33 nucleotides corresponding to miRNAs and YRNAs, respectively. Among YRNAs, predominantly fragments of RNY4 and RNY5 were detected. Plasma miRNAs and YRNAs were measured in 125 patients with a history of ACS who had undergone detailed assessment of platelet function 30 days after the acute event. Using quantitative real-time polymerase chain reactions, 92 miRNAs were assessed in ACS patients on different anti-platelet therapies. Key platelet-related miRNAs and YRNAs were correlated with platelet function tests. MiR-223 (rp=0.28, n=121, P=0.002), miR-126 (rp=0.22, n=121, P=0.016), other abundant platelet miRNAs and YRNAs showed significant positive correlations with the vasodilator-stimulated phosphoprotein phosphorylation assay. YRNAs, miR-126 and miR-223 were also among the small RNAs showing the greatest dependency on platelets, and strongly correlated with plasma levels of P-selectin, platelet factor 4 and platelet basic protein in the population-based Bruneck study (n=669). A single nucleotide polymorphism that facilitates processing of pri-miR-126 to mature miR-126 accounted for a rise in circulating platelet activation markers. Inhibition of miR-126 in mice reduced platelet aggregation. MiR-126 directly and indirectly affects ADAM9 and P2Y12 receptor expression. Levels of platelet-related plasma miRNAs and YRNAs correlate with platelet function tests in ACS patients and platelet activation markers in the general population. Alterations in miR-126 affect platelet reactivity.