Bazan Hernan A, Hatfield Samuel A, Brug Aaron, Brooks Ashton J, Lightell Daniel J, Woods T Cooper
From the Section of Vascular and Endovascular Surgery, Department of Surgery, Ochsner Clinic, New Orleans, LA (H.A.B., A.J.B.); The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA (H.A.B., A.J.B.); and Department of Physiology and the Heart & Vascular Institute, Tulane School of Medicine, New Orleans, LA (S.A.H., A.B., A.J.B., D.L., T.C.W.).
Circ Cardiovasc Genet. 2017 Aug;10(4). doi: 10.1161/CIRCGENETICS.117.001720.
Atherosclerotic plaque rupture is accompanied by an acute decrease in the carotid plaque expression of micro-RNAs (miRs)-221 and miR-222. Circular RNA (circR)-284 is a potential inhibitor of miR-221/miR-222 activity. We aimed to determine whether changes in the serum levels of these noncoding RNAs 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 noncoding RNA pairs to enhance the discriminatory power of noncoding RNAs as circulating biomarkers.
Serum levels of miR-221, miR-222, miR-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. miR-221 was significantly lower, whereas circR-284 was elevated in the serum of the urgent compared with the asymptomatic group. The ratio of serum circR-284:miR-221 was significantly elevated in the urgent group (=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 and 180 days of the carotid endarterectomy [symptomatic]) confirmed elevation of serum circR-284:miR-221 uniquely in the urgent group (<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 the use of functionally related pairs of circulating noncoding RNAs as biomarkers in cardiovascular disease.
动脉粥样硬化斑块破裂伴随着颈动脉斑块中微小RNA（miR）-221和miR-222表达的急性下降。环状RNA（circR）-284是miR-221/miR-222活性的潜在抑制剂。我们旨在确定在无症状的重度颈动脉疾病患者与急性有症状的颈动脉疾病患者及近期缺血性卒中患者中，是否能观察到这些非编码RNA血清水平的变化。此外，我们测试了使用功能相关的非编码RNA对来增强非编码RNA作为循环生物标志物的鉴别能力。
对24例无症状（无症状）和17例急性有症状患者（[紧急]在过去5天内发生缺血性脑血管事件）进行颈动脉内膜切除术时，测量其血清中miR-221、miR-222、miR-145和circR-284的水平。与无症状组相比，紧急组血清中miR-221显著降低，而circR-284升高。紧急组血清circR-284:miR-221的比值显著升高（=0.0002），并表现出作为指示颈动脉斑块破裂和卒中的生物标志物的良好特征。在112例患者（47例无症状，41例紧急，24例在颈动脉内膜切除术后5至180天发生脑血管事件[有症状]）中进行的验证研究证实，仅在紧急组中血清circR-284:miR-221升高（<0.001），且对检测斑块破裂和卒中有良好的敏感性和特异性。
血清circR-284:miR-221有潜力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非编码RNA对作为心血管疾病的生物标志物。
