Carotid Plaque Rupture Is Accompanied by an Increase in the Ratio of Serum circR-284 to miR-221 Levels.
Carotid Plaque Rupture Is Accompanied by an Increase in the Ratio of Serum circR-284 to miR-221 Levels.
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DOI：
10.1161/circgenetics.117.001720
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发表时间：
2017-08
期刊：
影响因子：
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通讯作者：
Woods TC
中科院分区：
文献类型：
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作者：
Bazan HA;Hatfield SA;Brug A;Brooks AJ;Lightell DJ Jr;Woods TC
动脉粥样硬化斑块破裂伴随着微RNA（miR）-221和-222的颈动脉斑块表达的急性减少。Circular RNA（circR）-284是miR-221/-222活性的潜在抑制剂。我们的目的是确定这些非编码RNA（ncRNA）的血清水平的变化是否观察到无症状的高级别颈动脉疾病患者与急性症状性颈动脉疾病和近期缺血性卒中患者。此外，我们测试了功能相关的ncRNA对的使用，以提高ncRNA作为循环生物标志物的区分能力。在接受颈动脉内膜切除术（CEA）的24例无症状（无症状）和17例急性症状（前5天内发生[紧急]缺血性脑血管事件）患者中测定了miR-221、-222、-145和circR-284的血清水平。与无症状组相比，急症组血清中miR-221显著降低，而circR-284升高。血清circR-284：miR-221的比率在紧急组中显著升高（p = 0.0002），并且表现出作为指示颈动脉斑块破裂和中风的生物标志物的有利特征。在112名患者（47名无症状患者，41名紧急患者和24名在CEA [症状]的5至180天之间发生脑血管事件的患者）中进行的验证研究证实了血清circR-284：miR-221的升高仅在紧急组中（p < 0.001），并且对于检测斑块破裂和中风具有良好的灵敏度和特异性。血清circR-284：miR-221有可能作为颈动脉斑块破裂和卒中的诊断生物标志物。此外，我们证明了使用功能相关的循环ncRNA对作为心血管疾病的生物标志物。
Atherosclerotic plaque rupture is accompanied by an acute decrease in the carotid plaque expression of microRNAs (miRs) -221 and -222. Circular RNA (circR)-284 is a potential inhibitor of miR-221/-222 activity. We aimed to determine whether changes in the serum levels of these non-coding RNAs (ncRNAs) are observed in patients with asymptomatic high-grade carotid disease versus patients with acutely symptomatic carotid disease and recent ischemic stroke. Additionally, we tested the use of functionally related ncRNA pairs to enhance the discriminatory power of ncRNAs as circulating biomarkers. Serum levels of miR -221,-222, -145 and circR-284 were measured in 24 asymptomatic (Asymptomatic) and 17 acutely symptomatic patients ([Urgent] ischemic cerebrovascular event within the previous 5 days) undergoing carotid endarterectomy (CEA). miR-221 was significantly lower while circR-284 was elevated in the serum of the Urgent compared to the Asymptomatic group. The ratio of serum circR-284:miR-221, was significantly elevated in the Urgent group (p = 0.0002) and exhibited favorable characteristics as a biomarker indicative of carotid plaque rupture and stroke. A validation study in 112 patients (47 Asymptomatic, 41 Urgent, and 24 patients with a cerebrovascular event between 5 to 180 days of the CEA [Symptomatic]) confirmed elevation of serum circR-284:miR-221 uniquely in the Urgent group (p < 0.001) and favorable sensitivity and specificity for detecting plaque rupture and stroke. Serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid plaque rupture and stroke. Moreover, we demonstrate use of functionally related pairs of circulating ncRNAs as biomarkers in cardiovascular disease.