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Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation

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Abstract

Purpose

Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA.

Methods

We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR).

Results

The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02).

Conclusion

Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.

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Funding

This study is supported by FAPESP (2012/02953-2).

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of São Paulo, São Paulo, Brazil

    Lunara S. Freitas

  2. Hypertension Unit, Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, Brazil

    Lunara S. Freitas, Valéria Costa-Hong, Fernanda M. Bernardes, Luiz A. Bortolotto & Luciano F. Drager

  3. Laboratory of Biochemistry and Molecular Biology of the Exercise, School of Physical Education and Sports, University of São Paulo, São Paulo, Brazil

    André C. Silveira & Edilamar M. Oliveira

  4. Sleep Laboratory, Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, Brazil

    Franco C. Martins & Geraldo Lorenzi-Filho

  5. Fleury Group, São Paulo, Brazil

    Adriana Lebkuchen & Karina H. M. Cardozo

  6. Hypertension Unit, Renal Division, University of São Paulo Medical School, São Paulo, Brazil

    Luciano F. Drager

Authors
  1. Lunara S. Freitas
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  2. André C. Silveira
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  6. Karina H. M. Cardozo
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  9. Geraldo Lorenzi-Filho
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  10. Edilamar M. Oliveira
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  11. Luciano F. Drager
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Contributions

Conceptualization: Luciano F. Drager, Edilamar M. Oliveira, Geraldo Lorenzi-Filho, Luiz A. Bortolotto

Methodology: Luciano F. Drager, Edilamar M. Oliveira, Lunara S. Freitas

Formal analysis and investigation: Lunara S. Freitas, André C. Silveira, Franco C. Martins, Valéria C. Hong, Adriana Lebkuchen, Karina H. M. Cardozo, Fernanda M. Bernardes, Luciano F. Drager, Edilamar M. Oliveira

Writing–original draft preparation: Lunara S. Freitas, André C. Silveira, Geraldo Lorenzi-Filho, Edilamar M. Oliveira, Luciano F. Drager

Writing–review and editing: Lunara S. Freitas, André C. Silveira, Geraldo Lorenzi-Filho, Edilamar M. Oliveira, Luciano F. Drager, Luiz A. Bortolotto

Funding acquisition: Edilamar M. Oliveira, Luciano F. Drager, Geraldo Lorenzi-Filho

Corresponding author

Correspondence to Luciano F. Drager.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study have been approved by the local Ethics Committee, under number CAAE: 26431314-8.0000.0068, in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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Freitas, L.S., Silveira, A.C., Martins, F.C. et al. Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation. Sleep Breath 24, 1463–1472 (2020). https://doi.org/10.1007/s11325-019-02003-1

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  • DOI: https://doi.org/10.1007/s11325-019-02003-1

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