Skip to main content
Log in

Effect of Nasal CPAP on SIRT1 and Endothelial Function in Obstructive Sleep Apnea Syndrome

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Background

Sirtuin 1 (SIRT1), a histone/protein deacetylase, has been implicated in aging, metabolism, and stress resistance. SIRT1 regulates endothelial nitric oxide (NO) synthase, restores NO availability, and is involved in different aspects of cardiovascular disease. The aim of this study was to evaluate any abnormalities with regard to SIRT1 protein level in the blood, SIRT1 activity, and impaired endothelial function in patients with obstructive sleep apnea syndrome (OSAS). We also investigated whether or not OSAS patients who received nasal continuous positive airway pressure (CPAP) treatment showed improvements in the levels of SIRT1.

Methods

Thirty-five patients with moderately severe to severe OSAS who requested nasal CPAP treatment and 20 healthy controls were prospectively enrolled. The SIRT1 protein levels in blood and its activity, and the serum levels of nitric oxide derivative (NO x ) were assessed. All subjects participated in sleep studies, which were repeated 3 months after nasal CPAP treatment in the patients with OSAS.

Results

In the patients with OSAS, the level of SIRT1 in the blood, its activity, and that of NO x was lower than those of normal subjects before nasal CPAP treatment. After nasal CPAP treatment, the level of SIRT1 in the blood and its activity increased from 0.55 ± 0.32 pg/μg of total protein and 3085.53 ± 1071.57 arbitrary fluorescence units (AFUs)/μg of total protein to 1.13 ± 0.43 pg/μg of total protein and 5344.65 ± 1579.71 AFUs/μg of total protein. The serum levels of NO x in the patients with OSAS increased from 16.36 ± 5.78 to 25.94 ± 5.17 µM.

Conclusions

Successful treatment for OSAS with nasal CPAP can restore blood levels of the SIRT1 protein and its activity and serum levels of NO x .

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

SIRT1:

Sirtuin 1

OSAS:

Obstructive sleep apnea syndrome

CPAP:

Continuous positive airway pressure

NO x :

Nitric oxide derivative

eNOS:

Endothelial nitric oxide synthase

COPD:

Chronic obstructive pulmonary disease

CS:

Cigarette smoke

AFUs:

Arbitrary fluorescence units

NAD+:

Nicotinamide adenine dinucleotide

HDAC:

Histone deacetylase

PBMC:

Peripheral blood mononuclear cells

BMI:

Body mass index

AHI:

Apnea–hypopnea index

SaO2 :

Arterial oxyhemoglobin saturation

References

  1. Lavie L (2003) Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev 7:35–51

    Article  PubMed  Google Scholar 

  2. Busse R, Fleming I (1995) Regulation and functional consequences of endothelial nitric oxide formation. Ann Med 27:331–340

    Article  CAS  PubMed  Google Scholar 

  3. Pankow W, Lies A, Lohmann FW (2000) Sleep-disordered breathing and hypertension. N Engl J Med 343:966

    Article  CAS  PubMed  Google Scholar 

  4. Ip MS, Lam B, Ng MM et al (2002) Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 165:670–676

    Article  PubMed  Google Scholar 

  5. Peker Y, Hedner J, Norum J et al (2002) Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med 166:159–165

    Article  PubMed  Google Scholar 

  6. Yao H, Rahman I (2012) Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence. Biochem Pharmacol 84:1332–1339

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zeng L, Chen R, Liang F et al (2009) Silent information regulator, Sirtuin 1, and age-related diseases. Geriatr Gerontol Int 9:7–15

    Article  PubMed  Google Scholar 

  8. Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Kruszewski M, Szumiel I (2005) Sirtuins (histone deacetylases III) in the cellular response to DNA damage—facts and hypotheses. DNA Repair (Amst) 4:1306–1313

    Article  CAS  Google Scholar 

  10. Yang XJ, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9:206–218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Rajendrasozhan S, Yang SR, Kinnula VL et al (2008) SIRT1, an anti-inflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177:861–870

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Rahman I, Kinnula VL, Gorbunova V et al (2012) SIRT1 as a therapeutic target in inflammaging of the pulmonary disease. Prev Med 54(Suppl):S20–S28

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Barnes PJ, Adcock IM, Ito K (2005) Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J 25:552–563

    Article  CAS  PubMed  Google Scholar 

  14. Ota H, Eto M, Ogawa S et al (2010) SIRT1/eNOS axis as a potential target against vascular senescence, dysfunction and atherosclerosis. J Atheroscler Thromb 17:431–435

    Article  CAS  PubMed  Google Scholar 

  15. Marin JM, Carrizo SJ, Vicente E et al (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 365:1046–1053

    Article  PubMed  Google Scholar 

  16. Iber C, Ancoli-Israel S, Chesson AL et al (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology, and technical specifications. American Academy of Sleep Medicine, Westchester

    Google Scholar 

  17. Sittipunt C, Steinberg KP, Ruzinski JT et al (2001) Nitric oxide and nitrotyrosine in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 163:503–510

    Article  CAS  PubMed  Google Scholar 

  18. Isajevs S, Strazda G, Kopeika U et al (2012) Different patterns of lung sirtuin expression in smokers with and without chronic obstructive pulmonary disease. Medicina (Kaunas) 48:552–557

    Google Scholar 

  19. Nakamaru Y, Vuppusetty C, Wada H et al (2009) A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J 23:2810–2819

    Article  CAS  PubMed  Google Scholar 

  20. Hwang JW, Sundar IK, Yao H et al (2014) Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. FASEB J 28:176–194

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Wang Q, Sun X, Li X et al (2015) Resveratrol attenuates intermittent hypoxia-induced insulin resistance in rats: involvement of Sirtuin 1 and the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway. Mol Med Rep 11:151–158

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Pillarisetti S (2008) A review of Sirt1 and Sirt1 modulators in cardiovascular and metabolic diseases. Recent Pat Cardiovasc Drug Discov 3:156–164

    Article  CAS  PubMed  Google Scholar 

  23. Hu YX, Cui H, Fan L et al (2013) Resveratrol attenuates left ventricular remodeling in old rats with COPD induced by cigarette smoke exposure and LPS instillation. Can J Physiol Pharmacol 91:1044–1054

    Article  CAS  PubMed  Google Scholar 

  24. Alonso-Fernández A, García-Río F, Arias MA et al (2009) Effects of CPAP on oxidative stress and nitrate efficiency in sleep apnoea: a randomised trial. Thorax 64:581–586

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Ministry of Science and Technology (Grant MOST 101-2314-B-195-015-MY2).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ching-Chi Lin.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, WJ., Liaw, SF., Lin, CC. et al. Effect of Nasal CPAP on SIRT1 and Endothelial Function in Obstructive Sleep Apnea Syndrome. Lung 193, 1037–1045 (2015). https://doi.org/10.1007/s00408-015-9790-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-015-9790-y

Keywords

Navigation