期刊
CIRCULATION
卷 124, 期 2, 页码 175-U154出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.110.012237
关键词
cytomegalovirus; hypertension; interferon regulatory factor-1; microRNAs
资金
- National Natural Science Foundation of China [81050012]
- Beijing Nova Program [2009B39]
- Beijing Natural Science Foundation [7102057]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars
- Education Ministry of China
Background-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. Methods and Results-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). Conclusions-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.
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