Up-regulation of circular RNA hsa_circ_0037909 promotes essential hypertension

Up-regulation of circular RNA hsa_circ_0037909 promotes essential hypertension
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DOI:
10.1002/jcla.22853
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发表时间:
2019-05-01
影响因子:
2.7
通讯作者:
Zhang, Lina
Zhang, Lina
中科院分区:
医学4区
文献类型:
--
作者:
Bao, Xingjie;He, Xin;Zhang, Lina

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原发性高血压(Essential hypertension,EH)是一种高患病率的疾病,面临着公共卫生的挑战.人们对诊断EH病因的遗传学知之甚少。环状RNA具有连续的共价闭合循环,不受RNA核酸外切酶的影响,且更稳定,不易降解,可能作为一种重要的生物活性物质参与EH的分子调控机制。方法采用qRT-PCR方法检测人全血及诱导培养的人主动脉内皮细胞(HAECs)和人脐静脉内皮细胞(HUVECs)中circRNA的表达。我们的病例对照研究涉及48对性别和年龄(+/- 3岁)匹配的病例对照。采用t检验、Pearson卡方检验和受试者工作特征曲线进行分析。结果hsa_circ_0037909在EH患者中的表达水平显著高于健康对照组(P = 0.007),hsa-miR-637在EH患者中的表达水平显著低于健康对照组(P = 0.039);在HAECs和HUVECs中的表达水平相同。将Hsa-miR-637(调整的P = 0.018)、hsa_circ_0037909(调整的P = 0.005)、HDL(调整的P = 0.024)和血清肌酐(调整的P = 0.014)纳入进行逻辑回归分析的模型中。经ROC曲线分析,两种RNA联合应用效果最好(P < 0.001)。Hsa_circ_0037909与血肌酐(P < 0.001)、低密度脂蛋白(P = 0.017)呈显著正相关。结论hsa_circ_0037911和hsa-miR-637联合检测可能是EH早期诊断的重要生物标志物。Hsa_circ_0037909可能影响血清肌酐或LDL,导致EH的形成。
Aims Essential hypertension (EH) is a high prevalence disease facing a public health challenge. People were little known about the genetics of diagnosing the cause of EH. Circular RNAs that have a continuous cycle of covalent closure, without affected by RNA exonuclease, and are more stable and hard to degrade may involve into the molecule regulation mechanism of EH as an important biomedical. Methods qRT-PCR was used to analyze circRNAs in total volume of human blood and the induced human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs). Our case-control study was involved with 48 pairs of case controls with sex and age (+/- 3 years) match. We conducted t test, Pearson's chi(2) test, and receiver operating characteristics (ROC) curve analysis for the corresponding analysis. Results The expression level of hsa_circ_0037909 in EH patients was significantly higher than that in the healthy controls (P = 0.007), and the expression level of hsa-miR-637 in EH patients was significantly lower in than that in the healthy controls (P = 0.039); the same result appears in the HAECs and HUVECs. Hsa-miR-637 (adjusted P = 0.018), hsa_circ_0037909 (adjusted P = 0.005), HDL (adjusted P = 0.024), and serum creatinine (adjusted P = 0.014) were brought into the model which performed logistic regression analysis. The combination of two RNAs was excellent (P < 0.001) through ROC curve analysis. Hsa_circ_0037909 was significantly positively correlated with serum creatinine (P < 0.001) and low-density lipoprotein (LDL) (P = 0.017). Conclusions Our findings suggested that the combination of hsa_circ_0037911 and hsa-miR-637 may be a significant important biomarker for early diagnosis of EH. Hsa_circ_0037909 may affect serum creatinine or LDL leading to the formation of EH.