Advertisement

Expression profile of long non-coding RNAs in rat models of OSA-induced cardiovascular disease: new insight into pathogenesis

  • Qingshi Chen
  • Guofu Lin
  • Jiefeng Huang
  • Gongping Chen
  • Xiaoyun Huang
  • Qichang Lin
Original Article
  • 7 Downloads

Abstract

Purpose

Long non-coding RNAs (lncRNAs) are a recently identified class of regulatory molecules involved in the regulation of numerous biological processes, but their functions in a rat model of chronic intermittent hypoxia (CIH) remain largely unknown. Therefore, for further investigation, we aimed to explore lncRNA expression profiles and reveal their potential functional roles in rat models of CIH.

Methods

We used a well-established CIH rat model and conducted lncRNA microarray experiments on the heart samples of rats with CIH and under normoxia control. Differentially expressed lncRNAs and mRNAs were identified via fold-change filtering and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics analyses were applied to reveal the potential roles of key lncRNAs. Co-expression analysis was conducted to determine the transcriptional regulatory relationship of lncRNAs and mRNAs between the two groups.

Results

Our data indicated that 157 lncRNAs and 319 mRNAs were upregulated, while 132 lncRNAs and 428 mRNAs were downregulated in the rat model of CIH compared with sham control. Pathway analyses showed that 31 pathways involved in upregulated transcripts and 28 pathways involved in downregulated transcripts. Co-expression networks were also constructed to explore the potential roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, XR_596701, XR_344474, XR_600374, ENSRNOT00000065561, XR_590196, and XR_597099, were validated by the use of qRT-PCR.

Conclusions

The present study first revealed lncRNAs expression profiles in a rat model of CIH, providing new insight into the pathogenesis of obstructive sleep apnea-induced cardiovascular disease.

Keywords

Long non-coding RNA Obstructive sleep apnea Cardiovascular disease Expression profiles 

Notes

Funding

This study is funded by the National Natural Science Foundation of China (grant number: 81370182 and 81870074), Quanzhou Science and Technology Projects (grant number: 2018N007S), and Startup Fund for Scientific Research, Fujian Medical University (grant number: 2017XQ1102).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable guidelines for the care and use of animals were followed.

Supplementary material

11325_2018_1753_Fig7_ESM.png (648 kb)
Fig S1

(PNG 648 kb)

11325_2018_1753_MOESM1_ESM.tif (2.8 mb)
High resolution image (TIF 2917 kb)
11325_2018_1753_Fig8_ESM.png (1.2 mb)
Fig S2

(PNG 1262 kb)

11325_2018_1753_MOESM2_ESM.tif (6.8 mb)
High resolution image (TIF 6977 kb)

References

  1. 1.
    Bradley TD, Floras JS (2009) Obstructive sleep apnoea and its cardiovascular consequences. LANCET 373:82–93CrossRefPubMedGoogle Scholar
  2. 2.
    Muxfeldt ES, Margallo VS, Guimaraes GM, Salles GF (2014) Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens 27:1069–1078CrossRefPubMedGoogle Scholar
  3. 3.
    Peppard PE, Young T, Palta M, Skatrud J (2000) Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 342:1378–1384CrossRefPubMedGoogle Scholar
  4. 4.
    Marin JM, Carrizo SJ, Vicente E, Agusti AG (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. LANCET 365:1046–1053CrossRefPubMedGoogle Scholar
  5. 5.
    Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939CrossRefPubMedGoogle Scholar
  6. 6.
    Ryan S, Taylor CT, McNicholas WT (2005) Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112:2660–2667CrossRefPubMedGoogle Scholar
  7. 7.
    Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570CrossRefPubMedGoogle Scholar
  8. 8.
    Somers VK, Dyken ME, Clary MP, Abboud FM (1995) Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96:1897–1904CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Schulz R, Seeger W, Fegbeutel C, Husken H, Bodeker RH, Tillmanns H, Grebe M (2005) Changes in extracranial arteries in obstructive sleep apnoea. Eur Respir J 25:69–74CrossRefPubMedGoogle Scholar
  10. 10.
    Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, O'Connor GT, Boland LL, Schwartz JE, Samet JM (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163:19–25CrossRefPubMedGoogle Scholar
  11. 11.
    Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. NATURE 458:223–227CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904–914CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159CrossRefPubMedGoogle Scholar
  14. 14.
    Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. NATURE 477:295–300CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. CELL 136:629–641CrossRefPubMedGoogle Scholar
  16. 16.
    Harries LW (2012) Long non-coding RNAs and human disease. Biochem Soc Trans 40:902–906CrossRefPubMedGoogle Scholar
  17. 17.
    Wang L, Ma X, Yan L, Wang T, Wen J, Mi G (2017) LncRNA SNHG1 negatively regulates miR-145a-5p to enhance NUAK1 expression and promote cancer cell metastasis and invasion in nasopharyngeal carcinoma. J Cell Physiol.  https://doi.org/10.1002/jcp.26340
  18. 18.
    Lai MC, Lin JG, Pai PY, Lai MH, Lin YM, Yeh YL, Cheng SM, Liu YF, Huang CY, Lee SD (2014) Protective effect of salidroside on cardiac apoptosis in mice with chronic intermittent hypoxia. Int J Cardiol 174:565–573CrossRefGoogle Scholar
  19. 19.
    Li S, Feng J, Wei S, Qian X, Cao J, Chen B (2016) Delayed neutrophil apoptosis mediates intermittent hypoxia-induced progressive heart failure in pressure-overloaded rats. Sleep Breath 20:95–102CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Uchida S, Dimmeler S (2015) Long noncoding RNAs in cardiovascular diseases. Circ Res 116:737–750CrossRefPubMedGoogle Scholar
  21. 21.
    Dumitrascu R, Heitmann J, Seeger W, Weissmann N, Schulz R (2013) Obstructive sleep apnea, oxidative stress and cardiovascular disease: lessons from animal studies. Oxidative Med Cell Longev 2013:234631CrossRefGoogle Scholar
  22. 22.
    Drager LF, Yao Q, Hernandez KL, Shin MK, Bevans-Fonti S, Gay J, Sussan TE, Jun JC, Myers AC, Olivecrona G, Schwartz AR, Halberg N, Scherer PE, Semenza GL, Powell DR, Polotsky VY (2013) Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4. Am J Respir Crit Care Med 188:240–248CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Almendros I, Farre R, Torres M, Bonsignore MR, Dalmases M, Ramirez J, Navajas D, Montserrat JM (2011) Early and mid-term effects of obstructive apneas in myocardial injury and inflammation. Sleep Med 12:1037–1040CrossRefPubMedGoogle Scholar
  24. 24.
    Yang D, Liu Z, Luo Q (2013) Plasma ghrelin and pro-inflammatory markers in patients with obstructive sleep apnea and stable coronary heart disease. Med Sci Monit 19:251–256CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Clark BS, Blackshaw S (2014) Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease. Front Genet 5:164CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154:26–46CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Qingshi Chen
    • 1
    • 2
  • Guofu Lin
    • 1
    • 3
    • 4
  • Jiefeng Huang
    • 1
    • 3
    • 4
  • Gongping Chen
    • 1
    • 3
    • 4
  • Xiaoyun Huang
    • 1
    • 3
    • 4
  • Qichang Lin
    • 1
    • 3
    • 4
  1. 1.Department of Respiratory DiseaseThe First Affiliated Hospital of Fujian Medical UniversityFuzhouChina
  2. 2.The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
  3. 3.Laboratory of Respiratory Disease of Fujian Medical UniversityFuzhouChina
  4. 4.Fujian Provincial Sleep-Disordered Breathing Clinic CenterFuzhouChina

Personalised recommendations