title: Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection.
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.
  
  
  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.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00420784.
authors.affiliation: Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Li
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhu
authors.forename: Weili
authors.initials: W
authors.lastname: Zhang
authors.forename: Youren
authors.initials: Y
authors.lastname: Chen
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Laurentiu M
authors.initials: LM
authors.lastname: Popescu
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wang
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Li
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wang
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.forename: Xinchun
authors.initials: X
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000150:complications; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000209:etiology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012367:RNA, Viral / Q000097:blood*; D012307:Risk Factors
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral