Skip to main content

Advertisement

SpringerLink
Log in

Inflammation in sleep apnea: An update

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Obstructive sleep apnea (OSA) is a common disorder associated with cardiovascular disease (CVD). One theory to explain this relationship proposes that OSA can induce systemic inflammation, thereby inducing CVD. This theory is based on the premise that obesity is a pro-inflammatory state, and that physiological derangements during sleep in subjects with OSA further aggravate inflammation. In support of this theory, some clinical studies have shown elevated inflammatory biomarkers in OSA subjects, or improvement in these markers following treatment of OSA. However, the data are inconsistent and often confounded by the effects of comorbid obesity. Animal models of OSA have been developed, which involve exposure of rodents or cells to intermittent hypoxia, a hallmark feature of OSA. Several of these experiments demonstrate that intermittent hypoxia can stimulate inflammatory pathways and lead to cardiovascular or metabolic pathology. In this review, we review relationships between OSA and inflammation, with particular attention to studies published within the last year.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gastaut H, Tassinari CA, Duron B. Polygraphic study of the episodic diurnal and nocturnal (hypnic and respiratory) manifestations of the Pickwick syndrome. Brain Res. 1966;1(2):167–86.

    CAS  PubMed  Google Scholar 

  2. Young T et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328(17):1230–5.

    CAS  PubMed  Google Scholar 

  3. Peppard PE et al. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284(23):3015–21.

    CAS  PubMed  Google Scholar 

  4. Berry RB et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the american academy of sleep medicine. J Clin Sleep Med. 2012;8(5):597–619.

    PubMed Central  PubMed  Google Scholar 

  5. Somers VK et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96(4):1897–904.

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Dempsey JA et al. Pathophysiology of sleep apnea. Physiol Rev. 2010;90(1):47–112.

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Dempsey JA, Forster HV. Mediation of ventilatory adaptations. Physiol Rev. 1982;62(1):262–346.

    CAS  PubMed  Google Scholar 

  8. Smith PL et al. Weight loss in mildly to moderately obese patients with obstructive sleep apnea. Ann Intern Med. 1985;103(6(Pt 1):850–5.

    Google Scholar 

  9. Weaver TE. Adherence to positive airway pressure therapy. Curr Opin Pulm Med. 2006;12(6):409–13.

    PubMed  Google Scholar 

  10. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc. 2008;5(2):173–8.

    PubMed Central  PubMed  Google Scholar 

  11. Ng A et al. Oral appliance therapy for obstructive sleep apnea. Treat Respir Med. 2005;4(6):409–22.

    PubMed  Google Scholar 

  12. Maurer JT. Surgical treatment of obstructive sleep apnea: standard and emerging techniques. Curr Opin Pulm Med. 2010;16(6):552–8.

    PubMed  Google Scholar 

  13. Strollo Jr PJ et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014;370(2):139–49.

    CAS  PubMed  Google Scholar 

  14. Mesarwi, O.A., et al., Metabolic dysfunction in obstructive sleep apnea: A critical examination of underlying mechanisms. Sleep Biol Rhythm, 2014: p. n/a-n/a.

  15. Cassel W et al. Risk of traffic accidents in patients with sleep-disordered breathing: reduction with nasal CPAP. Eur Respir J. 1996;9(12):2606–11.

    CAS  PubMed  Google Scholar 

  16. Montesi SB et al. The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2012;8(5):587–96.

    PubMed Central  PubMed  Google Scholar 

  17. Schein AS et al. Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients. J Hypertens. 2014;32(9):1762–73.

    CAS  PubMed  Google Scholar 

  18. Fava C et al. Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest. 2014;145(4):762–71.

    PubMed  Google Scholar 

  19. Punjabi NM et al. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol. 2004;160(6):521–30.

    PubMed  Google Scholar 

  20. Babu AR et al. Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea. Arch Intern Med. 2005;165(4):447–52.

    PubMed  Google Scholar 

  21. Drager LF, Jun J, Polotsky VY. Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis. Curr Opin Endocrinol Diabetes Obes. 2010;17(2):161–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Punjabi NM et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009;6(8):e1000132.

    PubMed Central  PubMed  Google Scholar 

  23. Young T et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31(8):1071–8.

    PubMed Central  PubMed  Google Scholar 

  24. Peker Y et al. Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med. 2002;166(2):159–65.

    PubMed  Google Scholar 

  25. Hung J et al. Association of sleep apnoea with myocardial infarction in men. Lancet. 1990;336(8710):261–4.

    CAS  PubMed  Google Scholar 

  26. Dyken ME et al. Investigating the relationship between stroke and obstructive sleep apnea. Stroke. 1996;27(3):401–7.

    CAS  PubMed  Google Scholar 

  27. Latina JM, Estes 3rd NA, Garlitski AC. The relationship between obstructive sleep apnea and atrial fibrillation: a complex interplay. Pulm Med. 2013;2013:621736.

    PubMed Central  PubMed  Google Scholar 

  28. Marin JM et al. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365(9464):1046–53.

    PubMed  Google Scholar 

  29. Arnaud C et al. Obstructive sleep apnea, immuno-inflammation, and atherosclerosis. Semin Immunopathol. 2009;31(1):113–25.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Jun J, Polotsky VY. Metabolic consequences of sleep-disordered breathing. ILAR J. 2009;50(3):289–306.

    CAS  PubMed  Google Scholar 

  31. Lavie L. Oxidative stress–a unifying paradigm in obstructive sleep apnea and comorbidities. Prog Cardiovasc Dis. 2009;51(4):303–12.

    CAS  PubMed  Google Scholar 

  32. Lavie L. Intermittent hypoxia: the culprit of oxidative stress, vascular inflammation and dyslipidemia in obstructive sleep apnea. Expert Rev Respir Med. 2008;2(1):75–84.

    CAS  PubMed  Google Scholar 

  33. McNicholas WT. Obstructive sleep apnea and inflammation. Prog Cardiovasc Dis. 2009;51(5):392–9.

    CAS  PubMed  Google Scholar 

  34. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–95.

    CAS  PubMed  Google Scholar 

  35. Liuzzo G et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994;331(7):417–24.

    CAS  PubMed  Google Scholar 

  36. Biasucci LM et al. Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation. 1999;99(16):2079–84.

    CAS  PubMed  Google Scholar 

  37. Koenig W et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (monitoring trends and determinants in cardiovascular disease) Augsburg cohort study, 1984 to 1992. Circulation. 1999;99(2):237–42.

    CAS  PubMed  Google Scholar 

  38. Haverkate F et al. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European concerted action on thrombosis and disabilities angina pectoris study group. Lancet. 1997;349(9050):462–6.

    CAS  PubMed  Google Scholar 

  39. Ridker PM et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336(14):973–9.

    CAS  PubMed  Google Scholar 

  40. Nordestgaard BG, Zacho J. Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander? Nutr Metab Cardiovasc Dis. 2009;19(8):521–4.

    CAS  PubMed  Google Scholar 

  41. Vasse M et al. Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular risk. Haemostasis. 1996;26 Suppl 4:331–9.

    CAS  PubMed  Google Scholar 

  42. Wilhelmsen L et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984;311(8):501–5.

    CAS  PubMed  Google Scholar 

  43. Gerner RR et al. Metabolic inflammation: role of cytokines in the crosstalk between adipose tissue and liver. Can J Physiol Pharmacol. 2013;91(11):867–72.

    CAS  PubMed  Google Scholar 

  44. Arner P. The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol Metab. 2003;14(3):137–45.

    CAS  PubMed  Google Scholar 

  45. Yudkin JS et al. Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study. Metabolism. 2004;53(7):852–7.

    CAS  PubMed  Google Scholar 

  46. Visser M et al. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999;282(22):2131–5.

    CAS  PubMed  Google Scholar 

  47. Gottlieb DJ et al. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med. 2014;370(24):2276–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Chirinos JA et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med. 2014;370(24):2265–75.

    PubMed Central  PubMed  Google Scholar 

  49. Craig SE et al. Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial. Thorax. 2012;67(12):1090–6.

    PubMed  Google Scholar 

  50. Kohler M et al. CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial. Chest. 2013;144(3):896–902.

    PubMed  Google Scholar 

  51. Stradling, J.R., et al., Markers of inflammation: data from the MOSAIC randomised trial of CPAP for minimally symptomatic OSA. Thorax, 2014.

  52. Unuvar Dogan F et al. Relationships between obstructive sleep apnea syndrome, continuous positive airway pressure treatment, and inflammatory cytokines. Sleep Disord. 2014;2014:518920.

    PubMed Central  PubMed  Google Scholar 

  53. Kritikou I et al. Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females. Eur Respir J. 2014;43(1):145–55.

    PubMed  Google Scholar 

  54. Shamsuzzaman AS et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105(21):2462–4.

    CAS  PubMed  Google Scholar 

  55. Cheng TO. Could elevated C-reactive protein in patients with obstructive sleep apnea be due to obesity per se? Circulation. 2003;107(1):e9. author reply e9.

    PubMed  Google Scholar 

  56. Yokoe T et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation. 2003;107(8):1129–34.

    CAS  PubMed  Google Scholar 

  57. Kohler M et al. Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial. Thorax. 2009;64(1):67–73.

    CAS  PubMed  Google Scholar 

  58. Guilleminault C, Kirisoglu C, Ohayon MM. C-reactive protein and sleep-disordered breathing. Sleep. 2004;27(8):1507–11.

    PubMed  Google Scholar 

  59. Barcelo A et al. Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea. Am J Med. 2004;117(2):118–21.

    CAS  PubMed  Google Scholar 

  60. Ryan S et al. Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity. Thorax. 2007;62(6):509–14.

    PubMed Central  PubMed  Google Scholar 

  61. Sahlman J et al. The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea. J Sleep Res. 2010;19(2):341–8.

    PubMed  Google Scholar 

  62. Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2006;174(7):824–30.

    CAS  PubMed  Google Scholar 

  63. Gozal D et al. C-reactive protein and obstructive sleep apnea syndrome in children. Front Biosci (Elite Ed). 2012;4:2410–22.

    Google Scholar 

  64. Kheirandish-Gozal L et al. Plasma C-reactive protein in nonobese children with obstructive sleep apnea before and after adenotonsillectomy. J Clin Sleep Med. 2006;2(3):301–4.

    PubMed Central  PubMed  Google Scholar 

  65. Ciccone MM et al. Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in obstructive sleep apnea. Molecules. 2014;19(2):1651–62.

    PubMed  Google Scholar 

  66. Bottazzi B et al. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol. 2010;28:157–83.

    CAS  PubMed  Google Scholar 

  67. Yasunaga T et al. Plasma pentraxin 3 is a more potent predictor of endothelial dysfunction than high-sensitive C-reactive protein. Int Heart J. 2014;55(2):160–4.

    CAS  PubMed  Google Scholar 

  68. Kobukai, Y., et al., Morning Pentraxin3 levels reflect obstructive sleep apnea-related acute inflammation. J Appl Physiol (1985), 2014.

  69. Oh IS et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443(7112):709–12.

    Google Scholar 

  70. Ramanjaneya M et al. Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity. Endocrinology. 2010;151(7):3169–80.

    CAS  PubMed  Google Scholar 

  71. Leivo-Korpela S et al. Adipokines NUCB2/nesfatin-1 and visfatin as novel inflammatory factors in chronic obstructive pulmonary disease. Mediat Inflamm. 2014;2014:232167.

    Google Scholar 

  72. Tang CH et al. The anti-inflammatory and anti-apoptotic effects of nesfatin-1 in the traumatic rat brain. Peptides. 2012;36(1):39–45.

    CAS  PubMed  Google Scholar 

  73. Shen, P., et al., Decreased levels of serum nesfatin-1 in patients with obstructive sleep apnea syndrome. Sleep Breath, 2014.

  74. Emerging Risk Factors, C et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. 2012;367(14):1310–20.

    Google Scholar 

  75. Fibrinogen Studies C et al. Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the fibrinogen studies collaboration. Am J Epidemiol. 2007;166(8):867–79.

    Google Scholar 

  76. Shamsuzzaman, A., et al., Severity of obstructive sleep apnea is associated with elevated plasma fibrinogen in otherwise healthy patients. Sleep Breath, 2014.

  77. Basoglu OK et al. Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome. Ann Thorac Med. 2011;6(3):120–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Chin K et al. Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 1996;153(6 Pt 1):1972–6.

    CAS  PubMed  Google Scholar 

  79. Kaditis AG et al. Morning levels of fibrinogen in children with sleep-disordered breathing. Eur Respir J. 2004;24(5):790–7.

    CAS  PubMed  Google Scholar 

  80. Phillips CL et al. Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study. Thorax. 2012;67(7):639–44.

    PubMed  Google Scholar 

  81. Guardiola JJ et al. Hypercoagulability in patients with obstructive sleep apnea. Sleep Med. 2001;2(6):517–23.

    CAS  PubMed  Google Scholar 

  82. Nizankowska-Jedrzejczyk A et al. Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial. J Clin Sleep Med. 2014;10(3):255–62.

    PubMed Central  PubMed  Google Scholar 

  83. Nojgaard C et al. Serum levels of YKL-40 increases in patients with acute myocardial infarction. Coron Artery Dis. 2008;19(4):257–63.

    PubMed  Google Scholar 

  84. Nielsen AR et al. Plasma YKL-40: a BMI-independent marker of type 2 diabetes. Diabetes. 2008;57(11):3078–82.

    PubMed Central  CAS  PubMed  Google Scholar 

  85. Kazakova M et al. Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis. Rheumatol Int. 2013;33(2):341–6.

    CAS  PubMed  Google Scholar 

  86. Letuve S et al. YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. J Immunol. 2008;181(7):5167–73.

    CAS  PubMed  Google Scholar 

  87. Wang X, Xing GH. Serum YKL-40 concentrations are elevated and correlated with disease severity in patients with obstructive sleep apnea syndrome. Scand J Clin Lab Invest. 2014;74(1):74–8.

    CAS  PubMed  Google Scholar 

  88. Li W, Yu Z, Jiang C. Association of serum YKL-40 with the presence and severity of obstructive sleep apnea syndrome. Lab Med. 2014;45(3):220–5.

    PubMed  Google Scholar 

  89. Oh DY et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142(5):687–98.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Ichimura A et al. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature. 2012;483(7389):350–4.

    CAS  PubMed  Google Scholar 

  91. Gozal D et al. Obstructive sleep apnea and obesity are associated with reduced GPR 120 plasma levels in children. Sleep. 2014;37(5):935–41.

    PubMed Central  PubMed  Google Scholar 

  92. Dovizio M et al. Role of platelets in inflammation and cancer: novel therapeutic strategies. Basic Clin Pharmacol Toxicol. 2014;114(1):118–27.

    CAS  PubMed  Google Scholar 

  93. Jun J et al. Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis. 2010;209(2):381–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  94. Gautier-Veyret E et al. Intermittent hypoxia-activated cyclooxygenase pathway: role in atherosclerosis. Eur Respir J. 2013;42(2):404–13.

    CAS  PubMed  Google Scholar 

  95. Beaudin AE et al. Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea. J Am Heart Assoc. 2014;3(3):e000875.

    PubMed Central  PubMed  Google Scholar 

  96. Akkaya, E., M. Gul, and M. Ugur, Platelet to lymphocyte ratio: A simple and valuable prognostic marker for acute coronary syndrome. Int J Cardiol, 2014.

  97. Thomson SP, McMahon LJ, Nugent CA. Endogenous cortisol: a regulator of the number of lymphocytes in peripheral blood. Clin Immunol Immunopathol. 1980;17(4):506–14.

    CAS  PubMed  Google Scholar 

  98. Nelson DH et al. Blood levels of 17-hydroxycorticosteroids following the administration of adrenal steroids and their relation to levels of circulating leukocytes. J Clin Invest. 1952;31(9):843–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Koseoglu, H.I., et al., Platelet-lymphocyte ratio is an independent predictor for cardiovascular disease in obstructive sleep apnea syndrome. J Thromb Thrombolysis, 2014.

  100. Kassi E et al. Role of vitamin D in atherosclerosis. Circulation. 2013;128(23):2517–31.

    PubMed  Google Scholar 

  101. Kheirandish-Gozal L, Peris E, Gozal D. Vitamin D levels and obstructive sleep apnoea in children. Sleep Med. 2014;15(4):459–63.

    PubMed  Google Scholar 

  102. Drager LF, Jun JC, Polotsky VY. Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea. Best Pract Res Clin Endocrinol Metab. 2010;24(5):843–51.

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Jun J, Polotsky VY. Sleep disordered breathing and metabolic effects: evidence from animal models. Sleep Med Clin. 2007;2(2):263–77.

    PubMed Central  PubMed  Google Scholar 

  104. Jun, J.C., et al., Intermittent Hypoxia-Induced Glucose Intolerance is Abolished by Alpha-Adrenergic Blockade or Adrenal Medullectomy. Am J Physiol Endocrinol Metab, 2014: p. ajpendo 00373 2014.

  105. Regazzetti C et al. Hypoxia decreases insulin signaling pathways in adipocytes. Diabetes. 2009;58(1):95–103.

    PubMed Central  CAS  PubMed  Google Scholar 

  106. Trayhurn P, Wang B, Wood IS. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity? Br J Nutr. 2008;100(2):227–35.

    CAS  PubMed  Google Scholar 

  107. Drager LF et al. Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4. Am J Respir Crit Care Med. 2013;188(2):240–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  108. He Q et al. Regulation of HIF-1{alpha} activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia. Am J Physiol Endocrinol Metab. 2011;300(5):E877–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  109. Lee YS et al. Increased adipocyte O2 consumption triggers HIF-1alpha, causing inflammation and insulin resistance in obesity. Cell. 2014;157(6):1339–52.

    CAS  PubMed  Google Scholar 

  110. Shin MK et al. The effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia. Respir Physiol Neurobiol. 2014;203C:60–7.

    Google Scholar 

  111. Poulain L et al. Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis. Eur Respir J. 2014;43(2):513–22.

    CAS  PubMed  Google Scholar 

  112. Barcelo A et al. Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea. Eur Respir J. 2011;37(6):1418–23.

    CAS  PubMed  Google Scholar 

  113. Jun J et al. Intermittent hypoxia has organ-specific effects on oxidative stress. Am J Physiol Regul Integr Comp Physiol. 2008;295(4):R1274–81.

    PubMed Central  CAS  PubMed  Google Scholar 

  114. Kanagy NL. Vascular effects of intermittent hypoxia. ILAR J. 2009;50(3):282–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005;112(17):2660–7.

    CAS  PubMed  Google Scholar 

  116. Jun JC et al. Effects of sleep apnea on nocturnal free fatty acids in subjects with heart failure. Sleep. 2011;34(9):1207–13.

    PubMed Central  PubMed  Google Scholar 

  117. Sniderman AD, Cianflone K. Substrate delivery as a determinant of hepatic apoB secretion. Arterioscler Thromb. 1993;13(5):629–36.

    CAS  PubMed  Google Scholar 

  118. Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003;14(3):281–7.

    CAS  PubMed  Google Scholar 

  119. Zhou S et al. Deletion of metallothionein exacerbates intermittent hypoxia-induced oxidative and inflammatory injury in aorta. Oxid Med Cell Longev. 2014;2014:141053.

    PubMed Central  PubMed  Google Scholar 

  120. Cai L et al. Metallothionein in radiation exposure: its induction and protective role. Toxicology. 1999;132(2–3):85–98.

    CAS  PubMed  Google Scholar 

  121. Badran M et al. Chronic intermittent hypoxia causes endothelial dysfunction in a mouse model of diet-induced obesity. Sleep Med. 2014;15(5):596–602.

    PubMed  Google Scholar 

  122. Kaur C et al. Increased vascular permeability and nitric oxide production in response to hypoxia in the pineal gland. J Pineal Res. 2007;42(4):338–49.

    CAS  PubMed  Google Scholar 

  123. Hung MW et al. Melatonin ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in rats with chronic intermittent hypoxia. J Pineal Res. 2013;55(3):247–56.

    CAS  PubMed  Google Scholar 

  124. Totoson P et al. Atorvastatin protects against deleterious cardiovascular consequences induced by chronic intermittent hypoxia. Exp Biol Med (Maywood). 2013;238(2):223–32.

    CAS  Google Scholar 

  125. Smith SM, Friedle SA, Watters JJ. Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial inflammatory and TLR4 gene expression. PLoS One. 2013;8(12):e81584.

    PubMed Central  PubMed  Google Scholar 

  126. Trotta T et al. Biological role of Toll-like receptor-4 in the brain. J Neuroimmunol. 2014;268(1–2):1–12.

    CAS  PubMed  Google Scholar 

  127. Gozal E et al. Proteomic analysis of CA1 and CA3 regions of rat hippocampus and differential susceptibility to intermittent hypoxia. J Neurochem. 2002;83(2):331–45.

    CAS  PubMed  Google Scholar 

  128. Guven SF et al. The prevalence of obstructive sleep apnea in patients with difficult-to-treat asthma. Asian Pac J Allergy Immunol. 2014;32(2):153–9.

    PubMed  Google Scholar 

  129. Lu, Y., et al., [Treatment of obstructive sleep apnea-hypopnea syndrome for children refractory asthma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2014. 49(6): p. 462–7.

  130. Reinke C et al. Chronic intermittent hypoxia induces lung growth in adult mice. Am J Physiol Lung Cell Mol Physiol. 2011;300(2):L266–73.

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Philippe, C., et al., Airway cell involvement in intermittent hypoxia-induced airway inflammation. Sleep Breath, 2014.

  132. Dancey DR et al. Impact of menopause on the prevalence and severity of sleep apnea. Chest. 2001;120(1):151–5.

    CAS  PubMed  Google Scholar 

  133. Bixler EO et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med. 2001;163(3 Pt 1):608–13.

    CAS  PubMed  Google Scholar 

  134. Gottlieb DJ et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation. 2010;122(4):352–60.

    PubMed Central  PubMed  Google Scholar 

  135. Campos-Rodriguez F et al. Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort. Am J Respir Crit Care Med. 2013;187(1):99–105.

    PubMed  Google Scholar 

  136. Torres M et al. Effect of ovariectomy on inflammation induced by intermittent hypoxia in a mouse model of sleep apnea. Respir Physiol Neurobiol. 2014;202:71–4.

    PubMed  Google Scholar 

  137. Somers VK, Abboud FM. Chemoreflexes–responses, interactions and implications for sleep apnea. Sleep. 1993;16(8 Suppl):S30–3.

    CAS  PubMed  Google Scholar 

  138. Somers VK et al. Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J Appl Physiol (1985). 1989;67(5):2101–6.

    CAS  Google Scholar 

  139. Stamatakis KA, Punjabi NM. Effects of sleep fragmentation on glucose metabolism in normal subjects. Chest. 2010;137(1):95–101.

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Deibert DC, Defronzo RA. Epinephrine-induced insulin resistance in man. J Clin Invest. 1980;65(3):717–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  141. Halberg N et al. Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol. 2009;29(16):4467–83.

    PubMed Central  CAS  PubMed  Google Scholar 

  142. Chinen I et al. Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats. Endocrinology. 2007;148(1):160–5.

    CAS  PubMed  Google Scholar 

  143. Imrie H, Abbas A, Kearney M. Insulin resistance, lipotoxicity and endothelial dysfunction. Biochim Biophys Acta. 2010;1801(3):320–6.

    CAS  PubMed  Google Scholar 

  144. Chouchou F et al. Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study. Eur Heart J. 2013;34(28):2122–31. 2131a.

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

Dr. Dileep Unnikrishnan has no conflicts of interests to declare. Dr. Vsevolod Y. Polotsky is supported by the NIH R01 HL-080105 grant and ResMed Foundation grant 90048207. Dr. Jonathan Jun is supported by the NIH grants K08 HL-109475 and Diabetes Research and Training Pilot & Feasibility Grant 114525-JHU-UMD and by American Academy of Sleep Medicine Foundation Junior Faculty Award 106-JF-14.

Author information

Authors and Affiliations

  1. Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Rm 5B.81, Baltimore, MD, 21224, USA

    Dileep Unnikrishnan, Jonathan Jun & Vsevolod Polotsky

Authors
  1. Dileep Unnikrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan Jun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vsevolod Polotsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Jun.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Unnikrishnan, D., Jun, J. & Polotsky, V. Inflammation in sleep apnea: An update. Rev Endocr Metab Disord 16, 25–34 (2015). https://doi.org/10.1007/s11154-014-9304-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-014-9304-x

Keywords

Search

Navigation