关键词: DNA methylation coagulation direct oral anticoagulants (DOACs) epigenetics miR-CRAFT microRNAs pathways pleiotropic effects

来  源:   DOI:10.3390/jpm14060562   PDF(Pubmed)

Abstract:
Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field. It is largely unknown whether epigenetic modifications interfere with DOAC response or whether DOAC treatment induces epigenetic modifications. To fill this gap, we started the miR-CRAFT (Circulating microRNAs and DNA methylation as regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation) research study. In miR-CRAFT, we follow, over time, changes in DNA methylation and microRNAs expression in naïve AF patients starting DOAC treatment. The ultimate goal of miR-CRAFT is to identify the molecular pathways epigenetically affected by DOACs, beyond the coagulation cascade, that are potentially mediating DOAC pleiotropic actions and to propose specific microRNAs as novel circulating biomarkers for DOAC therapy monitoring. We herein describe the study design and briefly present the progress in participant enrolment.
摘要:
直接口服抗凝剂(DOAC)是房颤(AF)患者血栓栓塞保护的标准治疗方法。表观遗传修饰,如DNA甲基化和microRNAs,已经成为房颤的潜在生物标志物。DOAC的表观遗传学仍然是一个研究不足的领域。表观遗传修饰是否干扰DOAC反应或DOAC治疗是否诱导表观遗传修饰在很大程度上是未知的。为了填补这个空白,我们开始了miR-CRAFT(循环微小RNA和DNA甲基化作为心房颤动中直接口服抗凝反应的调节因子)研究.在miR-CRAFT中,我们跟随,随着时间的推移,开始DOAC治疗的初始AF患者DNA甲基化和microRNAs表达的变化。miR-CRAFT的最终目标是鉴定受DOAC表观遗传影响的分子途径,除了凝血级联,它们可能介导DOAC多效作用,并提出特定的microRNA作为DOAC治疗监测的新型循环生物标志物。我们在此描述了研究设计,并简要介绍了参与者注册的进展。
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