Evidence map›Paper›PMID 27542393›Full record

ArticleCirculation2016

MicroRNA-21 Lowers Blood Pressure in Spontaneous Hypertensive Rats by Upregulating Mitochondrial Translation.

Huaping Li, Xiaorong Zhang, Feng Wang, Ling Zhou, Zhongwei Yin, Jiahui Fan, Xiang Nie, Peihua Wang, Xiang-Dong Fu, Chen Chen and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. NamiRNA-Enhancer Network: The Changing Era Challenge and Chance of miRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  7. Review
  8. Molecular mechanisms and intervention approaches of heart failure (Review).International journal of molecular medicine · 2025
    Review
  9. The roles of subcellular Argonaute 2 in cardiovascular diseases.Journal of translational internal medicine · 2025
    Article
  10. Review
  11. Article
  12. microRNA and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Guidelines for mitochondrial RNA analysis.Molecular therapy. Nucleic acids · 2024
    Review
  19. Article
  20. Review

62 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Huaping LiFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Xiaorong ZhangFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Feng WangFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Ling ZhouFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Zhongwei YinFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Jiahui FanFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Xiang NieFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Peihua WangFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Xiang-Dong FuFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.).
Chen ChenFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.). chenchen@tjh.tjmu.edu.cn dwwang@tjh.tjmu.edu.cn.
Dao Wen WangFrom Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.L., F.W., L.Z., Z.Y., J.F., X.N., P.W., C.C., D.W.W.); Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (X.Z., X.-D.F.); and Department of Cellular and Molecular Medicine and Institute of Genomic Medicine, University of California, San Diego, La Jolla (X.-D.F.). chenchen@tjh.tjmu.edu.cn dwwang@tjh.tjmu.edu.cn.
Institute of Biophysics · CNChinese Academy of Sciences · CN

Funding

FUNCTION &REGULATION OF THE HUMAN SPLICING FACTOR SC35R01GM049369 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FU, XIANG-DONG · 1993 to 2018
$7.2M
NIGMS NIH HHS R01 GM049369
6 · The paper itself

Abstract

backgroundExcessive reactive oxygen species generated in mitochondria has been implicated as a causal event in hypertensive cardiomyopathy. Multiple recent studies suggest that microRNAs (miRNAs) are able to translocate to mitochondria to modulate mitochondrial activities, but the medical significance of such a new miRNA function has remained unclear. Here, we characterized spontaneous hypertensive rats (SHRs) in comparison with Wistar rats, finding that micro RNA-21 (miR-21) was dramatically induced in SHRs relative to Wistar rats. We designed a series of experiments to determine whether miR-21 is involved in regulating reactive oxygen species generation in mitochondria, and if so, how induced miR-21 may either contribute to hypertensive cardiomyopathy or represent a compensatory response.

methodsWestern blotting was used to compare the expression of key nuclear genome (nDNA)-encoded and mitochondrial genome (mtDNA)-encoded genes involved in reactive oxygen species production in SHRs and Wistar rats. Bioinformatics was used to predict miRNA targets followed by biochemical validation using quantitative real-time polymerase chain reaction and Ago2 immunoprecipitation. The direct role of miRNA in mitochondria was determined by GW182 dependence, which is required for miRNA to function in the cytoplasm, but not in mitochondria. Recombinant adeno-associated virus (type 9) was used to deliver miRNA mimic to rats via tail vein, and blood pressure was monitored with a photoelectric tail-cuff system. Cardiac structure and functions were assessed by echocardiography and catheter manometer system.

resultsWe observed a marked reduction of mtDNA-encoded cytochrome b (mt-Cytb) in the heart of SHRs. Downregulation of mt-Cytb by small interfering RNA in mitochondria recapitulates some key disease features, including elevated reactive oxygen species production. Computational prediction coupled with biochemical analysis revealed that miR-21 directly targeted mt-Cytb to positively modulate mt-Cytb translation in mitochondria. Circulating miR-21 levels in hypertensive patients were significantly higher than those in controls, showing a positive correlation between miR-21 expression and blood pressure. Remarkably, recombinant adeno-associated virus-mediated delivery of miR-21 was sufficient to reduce blood pressure and attenuate cardiac hypertrophy in SHRs.

conclusionsOur findings reveal a positive function of miR-21 in mitochondrial translation, which is sufficient to reduce blood pressure and alleviate cardiac hypertrophy in SHRs. This observation indicates that induced miR-21 is part of the compensatory program and suggests a novel theoretical ground for developing miRNA-based therapeutics against hypertension.

Indexed as

AnimalsBlood PressureHypertensionMaleMicroRNAsMitochondriaRatsRats, Inbred SHRRats, WistarReactive Oxygen SpeciesTranscriptional ActivationUp-RegulationMicroRNAsmirn21 microRNA, ratReactive Oxygen Speciescytochrome bMIR-21 microRNA, humanmitochondriareactive oxygen species

Identifiers

PMID27542393
PMCPMC5515592
OpenAlexW2509340025

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.