Circulating miR-320a-3p and miR-483-5p level associated with pharmacokinetic-pharmacodynamic profiles of rivaroxaban.
Circulating miR-320a-3p and miR-483-5p level associated with pharmacokinetic-pharmacodynamic profiles of rivaroxaban.
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循环 miR-320a-3p 和 miR-483-5p 水平与利伐沙班的药代动力学-药效学特征相关
DOI：
10.1186/s40246-022-00445-5
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发表时间：
2022-12-28
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
个体化抗凝治疗的新生物标志物尚未确定。我们的目的是研究血浆miRNA与利伐沙班药代动力学-药效学（PK-PD）特征的相关性。这是一项在中国人群中进行的多中心、探索性miRNA研究。健康志愿者和接受利伐沙班的患者入组研究。在健康志愿者中测量0-t h的血药浓度-时间曲线下面积（AUC 0-t）和3 h时的抗Xa活性（AXA 3 h），在患者中测量AXA 3 h。采用miRNA芯片检测26例健康志愿者口服20 mg利伐沙班后的miRNA，并采用定量逆转录聚合酶链反应排除未检测到的miRNA。然后在65名健康志愿者和71名患者中定量miR-320 a-3 p和miR-483- 5 p。比较了AXA 3 h或AUC 0-t高和低受试者以及随访期间有或无出血的匹配患者3 h时的miRNA水平。通过TargetScan、miRTarBase和miRDB预测miRNA靶标。验证的基因包括在GO富集和KEGG分析中。蛋白质-蛋白质相互作用网络由STRING建立并由Cytoscape可视化。共有136例中国受试者完成了研究。在服用15 mg利伐沙班的健康志愿者中，3 h时的miR-320 a水平与AXA 3 h和AUC 0-t显著正相关（分别为r = 0.359，p = 0.025; r = 0.370，p = 0.02）。还观察到miR-483与AXA 3 h或AUC 0-t之间呈正相关（分别为r = 0.372，p = 0.02; r = 0.523，p = 0.001）。AUC 0-t较高组3 h时miR-320 a和miR-483水平显著高于0 h时。3 h时的miR-483水平可区分AXA 3 h或AUC 0-t高或低的健康志愿者。在10 mg进食亚组中，与对照组相比，还观察到3小时mir-483水平更高。在患者之间的比较中没有发现显著差异。生物信息学分析表明，这些miRNAs可能通过靶向ABCG 2、ITGB 3、PTEN、MAPK 1/3等发挥调控作用。在中国健康受试者中，发现miR-320 a和miR-483水平与利伐沙班的PK和PD特征相关。需要进一步的研究来验证这些发现并探讨其机制。在线版本包含补充材料，可通过10.1186/s40246-022-00445-5获得。
Novel biomarkers for personalizing anticoagulation remain undetermined. We aimed to investigate the association of plasma miRNAs with pharmacokinetic–pharmacodynamic (PK-PD) profiles of rivaroxaban. This is a multicenter, exploratory study of miRNAs in a Chinese population. Healthy volunteers and patients receiving rivaroxaban were enrolled in the study. The area under the plasma concentration–time curve from time 0-t h (AUC0-t) and anti-Xa activity at 3 h (AXA3h) were measured in healthy volunteers, and AXA3h was measured in patients. MiRNAs were detected by miRNA microarray in 26 healthy volunteers with 20 mg rivaroxaban, and quantitative reverse transcription polymerase chain reaction was used to exclude undetectable ones. MiR-320a-3p and miR-483-5p were then quantified in 65 healthy volunteers and 71 patients. MiRNA levels at 3 h were compared between high and low AXA3h or AUC0-t subjects and in matched patients with or without bleeding during follow-up. The miRNA targets were predicted by TargetScan, miRTarBase, and miRDB. Validated genes were included in GO enrichment and KEGG analyses. The protein–protein interaction network was established by STRING and visualized by Cytoscape. A total of 136 Chinese subjects completed the study. In healthy volunteers taking 15 mg rivaroxaban, the miR-320a level at 3 h was significantly positively correlated with AXA3h and AUC0-t (r = 0.359, p = 0.025; r = 0.370, p = 0.02, respectively). A positive correlation was also observed between miR-483 and AXA3h or AUC0-t (r = 0.372, p = 0.02; r = 0.523, p = 0.001, respectively). MiR-320a and miR-483 levels at 3 h in the higher AUC0-t group were significantly higher than those at 0 h. MiR-483 levels at 3 h may distinguish healthy volunteers with high or low AXA3h or AUC0-t. In the 10 mg fed subgroup, higher 3 h mir-483 levels were also observed compared with the control group. No significant differences were found in the comparisons among patients. Bioinformatic analysis showed that these miRNAs may play a regulatory role by targeting ABCG2, ITGB3, PTEN, MAPK1/3, etc. MiR-320a and miR-483 levels were found to be associated with PK and PD profiles of rivaroxaban in healthy Chinese subjects. Further studies are required to verify these findings and explore the mechanisms. The online version contains supplementary material available at 10.1186/s40246-022-00445-5.
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DOI：
10.1093/ejcts/ezw245
发表时间：
2017-01
期刊：
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
影响因子：
--
作者：
Harling L;Lambert J;Ashrafian H;Darzi A;Gooderham NJ;Athanasiou T
通讯作者：
Athanasiou T
影响因子：
--
作者：
Guidetti, Gianni F.;Canobbio, Ilaria;Torti, Mauro
通讯作者：
Torti, Mauro
影响因子：
7.3
作者：
Kang, Dong Woo;Yang, Eun Sun;Min, Do Sik
通讯作者：
Min, Do Sik
影响因子：
6.5
作者：
Lawrie, Charles H.;Gal, Shira;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
影响因子：
64.5
作者：
Eulalio, Ana;Huntzinger, Eric;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa