Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Circulation. 2011 Jul 12;124(2):175-84. doi: 10.1161/CIRCULATIONAHA.110.012237. Epub 2011 Jun 20.
Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension.
Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296-5p, let-7e, and a human cytomegalovirus [HCMV]-encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296-5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all P<0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112. Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%, P=0.0005; 1870 versus 54 copies per 1 mL plasma, P<0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15; P=0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46; P<0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27; P<0.0001, respectively).
We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension.
URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00420784.
原发性高血压已被认为是一种由环境和遗传因素共同作用导致的疾病。最近的研究表明 microRNAs（miRNAs）参与了心肌肥厚和心力衰竭。然而，miRNAs 在原发性高血压中的作用知之甚少。
我们使用基于微阵列的 miRNA 表达谱分析，比较了 13 名高血压患者和 5 名健康对照者的血浆样本中的 miRNA 表达。发现 27 个 miRNA 表达存在差异。在 24 名高血压患者和 22 名对照者的血浆样本中独立验证了选定 miRNA（miR-296-5p、let-7e 和人巨细胞病毒 [HCMV] 编码的 miRNA hcmv-miR-UL112）的表达。在 127 名患者和 67 名对照者中进一步确定了 hcmv-miR-UL112、miR-296-5p 和 let-7e 的绝对表达水平（倍数变化分别为 2.5、0.5 和 1.7；均 P<0.0001）。此外，我们证明干扰素调节因子 1 是 hcmv-miR-UL112 的直接靶标。与对照组相比，高血压组的 HCMV 血清阳性率和定量滴度均升高（52.7%比 30.9%，P=0.0005；1870 比每毫升血浆 54 拷贝，P<0.0001）。血清阳性率、HCMV 的对数转换拷贝数和 hcmv-miR-UL112 与高血压风险增加独立相关（比值比，2.48；95%置信区间，1.48 至 4.15；P=0.0005；比值比，1.97；95%置信区间，1.58 至 2.46；P<0.0001；比值比，2.55；95%置信区间，1.98 至 3.27；P<0.0001）。
我们首次报道了高血压患者的循环 miRNA 图谱，并证实了 HCMV 感染与原发性高血压之间的新联系。这些发现可能为原发性高血压的发病机制提供重要的见解。
