Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection.

Authors

• Shuqiang Li
• Jianguo Zhu
• Weili Zhang
• Youren Chen
• Ke Zhang
• Laurentiu M Popescu
• Xinliang Ma
• Wayne Bond Lau
• Rong Rong
• Xueqing Yu
• Bingbing Wang
• Yafeng Li
• Chuanshi Xiao
• Mingming Zhang
• Shuyan Wang
• Liping Yu
• Alex F Chen
• Xinchun Yang
• Jun Cai

Publication/Presentation Date

7-12-2011

Abstract

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.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00420784.

Volume

124

Issue

2

First Page

175

Last Page

184

ISSN

1524-4539

Published In/Presented At

Li, S., Zhu, J., Zhang, W., Chen, Y., Zhang, K., Popescu, L. M., Ma, X., Lau, W. B., Rong, R., Yu, X., Wang, B., Li, Y., Xiao, C., Zhang, M., Wang, S., Yu, L., Chen, A. F., Yang, X., & Cai, J. (2011). Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation, 124(2), 175–184. https://doi.org/10.1161/CIRCULATIONAHA.110.012237

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

21690488

Department(s)

Administration and Leadership

Document Type

Article