Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 8215082, 10 pages
http://dx.doi.org/10.1155/2016/8215082
Review Article

Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective

1Cardiovascular Diseases Centre, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
2China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100091, China

Received 10 February 2016; Revised 1 April 2016; Accepted 20 April 2016

Academic Editor: Gopi Kolluru

Copyright © 2016 Linqin Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. H. A. Chami, H. E. Resnick, S. F. Quan, and D. J. Gottlieb, “Association of incident cardiovascular disease with progression of sleep-disordered breathing,” Circulation, vol. 123, no. 12, pp. 1280–1286, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. Y. Peker, J. Hedner, J. Norum, H. Kraiczi, and J. Carlson, “Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up,” American Journal of Respiratory and Critical Care Medicine, vol. 166, no. 2, pp. 159–165, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. P. Gopalakrishnan and T. Tak, “Obstructive sleep apnea and cardiovascular disease,” Cardiology in Review, vol. 19, no. 6, pp. 279–290, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. T. D. Bradley and J. S. Floras, “Obstructive sleep apnoea and its cardiovascular consequences,” The Lancet, vol. 373, no. 9657, pp. 82–93, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. V. A. Rossi, J. R. Stradling, and M. Kohler, “Effects of obstructive sleep apnoea on heart rhythm,” European Respiratory Journal, vol. 41, no. 6, pp. 1439–1451, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. A. S. Gami, E. J. Olson, W. K. Shen et al., “Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults,” Journal of the American College of Cardiology, vol. 62, no. 7, pp. 610–616, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. L. F. Drager, V. Y. Polotsky, and G. Lorenzi-Filho, “Obstructive sleep apnea: an emerging risk factor for atherosclerosis,” Chest, vol. 140, no. 2, pp. 534–542, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. G. D. Foster, K. E. Borradaile, M. H. Sanders et al., “A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the sleep AHEAD study,” Archives of Internal Medicine, vol. 169, no. 17, pp. 1619–1626, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. T.-Y. Tan, C.-W. Liou, M. Friedman, H.-C. Lin, H.-W. Chang, and M.-C. Lin, “Factors associated with increased carotid intima-media thickness in obstructive sleep apnea/hypopnea syndrome,” Neurologist, vol. 18, no. 5, pp. 277–281, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Jun, C. Reinke, D. Bedja et al., “Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice,” Atherosclerosis, vol. 209, no. 2, pp. 381–386, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. D. Song, G. Fang, S.-Z. Mao et al., “Chronic intermittent hypoxia induces atherosclerosis by NF-κB-dependent mechanisms,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1822, no. 11, pp. 1650–1659, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. H. A. Chami, H. E. Resnick, S. F. Quan, and D. J. Gottlieb, “Association of incident cardiovascular disease with progression of sleep-disordered breathing,” Circulation, vol. 123, no. 12, pp. 1280–1286, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. B.-X. Liu, R. Guo, S.-P. Zhou, S. Xie, K. Wang, and Y. Xu, “Effects of obstructive sleep apnea on cardiac function and clinical outcomes in Chinese patients with ST-elevation myocardial infarction,” The Scientific World Journal, vol. 2014, Article ID 908582, 13 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Turmel, F. Sériès, L.-P. Boulet et al., “Relationship between atherosclerosis and the sleep apnea syndrome: an intravascular ultrasound study,” International Journal of Cardiology, vol. 132, no. 2, pp. 203–209, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. S. K. Sharma, E. V. Reddy, A. Sharma et al., “Prevalence and risk factors of syndrome Z in urban Indians,” Sleep Medicine, vol. 11, no. 6, pp. 562–568, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. I. W. Seetho, R. Asher, R. J. Parker et al., “Effect of CPAP on arterial stiffness in severely obese patients with obstructive sleep apnoea,” Sleep and Breathing, vol. 19, no. 4, pp. 1155–1165, 2015. View at Publisher · View at Google Scholar · View at Scopus
  17. F. Li, H. Huang, L. Song, H. Hao, and M. Ying, “Effects of obstructive sleep apnea hypopnea syndrome on blood pressure and c-reactive protein in male hypertension patients,” Journal of Clinical Medicine Research, vol. 8, no. 3, pp. 220–224, 2016. View at Publisher · View at Google Scholar
  18. L. N. Diogo, S. A. Pereira, A. R. Nunes, R. A. Afonso, A. I. Santos, and E. C. Monteiro, “Efficacy of carvedilol in reversing hypertension induced by chronic intermittent hypoxia in rats,” European Journal of Pharmacology, vol. 765, pp. 58–67, 2015. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Palla, M. Digiorgio, N. Carpenè et al., “Sleep apnea in morbidly obese patients: prevalence and clinical predictivity,” Respiration, vol. 78, no. 2, pp. 134–140, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. A. R. Schwartz, S. P. Patil, A. M. Laffan, V. Polotsky, H. Schneider, and P. L. Smith, “Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches,” Proceedings of the American Thoracic Society, vol. 5, no. 2, pp. 185–192, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. D. Lv, L. Tan, Y. Wu, C. Cao, and Z. Deng, “Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea: a HuGE review and meta-analysis,” Sleep and Breathing, vol. 19, no. 3, pp. 1073–1078, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. Z. Sun and W. Shen, “Effect of intermittent hypoxia on lipid metabolism in liver cells and the underlying mechanism,” Zhonghua Gan Zang Bing Za Zhi, vol. 22, no. 5, pp. 369–373, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. N. M. Punjabi and B. A. Beamer, “Alterations in glucose disposal in sleep-disordered breathing,” American Journal of Respiratory and Critical Care Medicine, vol. 179, no. 3, pp. 235–240, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. R. Tkacova, W. T. McNicholas, M. Javorsky et al., “Nocturnal intermittent hypoxia predicts prevalent hypertension in the European Sleep Apnoea Database cohort study,” European Respiratory Journal, vol. 44, no. 4, pp. 931–941, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. H.-J. Xu, H.-L. Yi, J. Guan, and S.-K. Yin, “Effect of continuous positive airway pressure on lipid profile in patients with obstructive sleep apnea syndrome: a meta-analysis of randomized controlled trials,” Atherosclerosis, vol. 234, no. 2, pp. 446–453, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Yoshikawa, M. Yamauchi, Y. Fujita et al., “The impact of obstructive sleep apnea and nasal CPAP on circulating adiponectin levels,” Beiträge Zur Klinik Der Tuberkulose, vol. 192, no. 2, pp. 289–295, 2014. View at Publisher · View at Google Scholar
  27. E. Martínez-Ceron, I. Fernández-Navarro, and F. Garcia-Rio, “Effects of continuous positive airway pressure treatment on glucose metabolism in patients with obstructive sleep apnea,” Sleep Medicine Reviews, vol. 25, pp. 121–130, 2016. View at Publisher · View at Google Scholar · View at Scopus
  28. E. Martínez-Cerón, B. Barquiel, A. M. Bezos et al., “Effect of CPAP on glycemic control in patients with obstructive sleep apnea and type 2 diabetes. a randomized clinical trial,,” American Journal of Respiratory and Critical Care Medicine, 2016. View at Publisher · View at Google Scholar
  29. W. Kukwa, R. Glowczynska, K. J. Filipiak et al., “Serum EPO and VEGF levels in patients with sleep-disordered breathing and acute myocardial infarction,” Sleep & Breathing, vol. 17, no. 3, pp. 1063–1069, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. F. S. Luyster, K. E. Kip, A. N. Aiyer, S. E. Reis, and P. J. Strollo Jr., “Relation of obstructive sleep apnea to coronary artery calcium in non-obese versus obese men and women aged 45-75 years,” The American Journal of Cardiology, vol. 114, no. 11, pp. 1690–1694, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. Y. Kwon, D. A. Duprez, D. R. Jacobs et al., “Obstructive sleep apnea and progression of coronary artery calcium: the multi-ethnic study of atherosclerosis study,” Journal of the American Heart Association, vol. 3, no. 5, Article ID e001241, 2014. View at Google Scholar · View at Scopus
  32. A. S. Jordan, D. G. Mcsharry, and M. Atul, “Adult obstructive sleep apnoea,” The Lancet, vol. 383, no. 9918, pp. 736–747, 2014. View at Publisher · View at Google Scholar
  33. C.-H. Lee, S.-M. Khoo, B.-C. Tai et al., “Obstructive sleep apnea in patients admitted for acute myocardial infarction: prevalence, predictors, and effect on microvascular perfusion,” Chest, vol. 135, no. 6, pp. 1488–1495, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Libby, “Inflammation in atherosclerosis,” Arteriosclerosis Thrombosis & Vascular Biology, vol. 32, no. 9, pp. 2045–2051, 2012. View at Google Scholar
  35. A. J. Merched, K. Ko, K. H. Gotlinger, C. N. Serhan, and L. Chan, “Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators,” The FASEB Journal, vol. 22, no. 10, pp. 3595–3606, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Anogeianaki, D. Angelucci, E. Cianchetti et al., “Atherosclerosis: a classic inflammatory disease,” International Journal of Immunopathology and Pharmacology, vol. 24, no. 4, pp. 817–825, 2011. View at Google Scholar · View at Scopus
  37. I. Muraki, T. Tanigawa, K. Yamagishi et al., “Nocturnal intermittent hypoxia and C reactive protein among middle-aged community residents: a cross-sectional survey,” Thorax, vol. 65, no. 6, pp. 523–527, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. V. Y. Polotsky, V. Savransky, S. Bevans-Fonti et al., “Intermittent and sustained hypoxia induce a similar gene expression profile in human aortic endothelial cells,” Physiological Genomics, vol. 41, no. 3, pp. 306–314, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. M.-W. Hung, G. M. Kravtsov, C.-F. Lau, A. M.-S. Poon, G. L. Tipoe, and M.-L. Fung, “Melatonin ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in rats with chronic intermittent hypoxia,” Journal of Pineal Research, vol. 55, no. 3, pp. 247–256, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Arnaud, P. C. Beguin, G. Pelli et al., “Intermittent hypoxia induces inflammatory vascular remodeling in C57BL6 mice,” European Journal of Clinical Investigation, vol. 38, article 37, 2008. View at Google Scholar
  41. Q. Han, S. C. Yeung, M. S. M. Ip, and J. C. W. Mak, “Intermittent hypoxia-induced NF-κB and HO-1 regulation in human endothelial EA.hy926 cells,” Cell Biochemistry & Biophysics, vol. 66, no. 3, pp. 431–441, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Y. Lee, Y. Wang, J. C. Mak, and M. S. Ip, “Intermittent hypoxia induces NF-κB-dependent endothelial activation via adipocyte-derived mediators,” American Journal of Physiology—Cell Physiology, vol. 310, no. 6, pp. C446–C455, 2016. View at Publisher · View at Google Scholar
  43. S. Ryan, W. T. McNicholas, and C. T. Taylor, “A critical role for p38 map kinase in NF-κB signaling during intermittent hypoxia/reoxygenation,” Biochemical and Biophysical Research Communications, vol. 355, no. 3, pp. 728–733, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Del Rio, E. A. Moya, and R. Iturriaga, “Contribution of inflammation on carotid body chemosensory potentiation induced by intermittent hypoxia,” Advances in Experimental Medicine and Biology, vol. 758, pp. 199–205, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. H.-J. Eisele, P. Markart, and R. Schulz, “Obstructive sleep apnea, oxidative stress, and cardiovascular disease: evidence from human studies,” Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 608438, 9 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  46. G. L. Semenza and N. R. Prabhakar, “Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea,” Journal of Applied Physiology, vol. 119, no. 10, pp. 1152–1156, 2015. View at Publisher · View at Google Scholar
  47. E. Vatansever, E. Surmen-Gur, A. Ursavas, and M. Karadag, “Obstructive sleep apnea causes oxidative damage to plasma lipids and proteins and decreases adiponectin levels,” Sleep and Breathing, vol. 15, no. 3, pp. 275–282, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. Q.-B. Liu, L.-L. Liu, Y.-M. Lu et al., “The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells,” Toxicology & Applied Pharmacology, vol. 244, no. 3, pp. 374–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. L. Lavie and P. Lavie, “Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link,” European Respiratory Journal, vol. 33, no. 6, pp. 1467–1484, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Lavie, “Intermittent hypoxia: the culprit of oxidative stress, vascular inflammation and dyslipidemia in obstructive sleep apnea,” Expert Review of Respiratory Medicine, vol. 2, no. 1, pp. 75–84, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. U. C. S. Yadav, V. Rani, G. Deep, R. K. Singh, and K. Palle, “Oxidative stress in metabolic disorders: pathogenesis, prevention, and therapeutics,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 9137629, 3 pages, 2016. View at Publisher · View at Google Scholar
  52. S.-S. Zhou, Y.-G. Wang, Y. Tan et al., “Deletion of metallothionein exacerbates intermittent hypoxia-induced oxidative and inflammatory injury in aorta,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 141053, 11 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. A. M. Rifai, M. G. Silverman, K. Nasir et al., “The association of nonalcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA),” Atherosclerosis, vol. 239, no. 2, pp. 629–633, 2015. View at Publisher · View at Google Scholar
  54. V. Savransky, A. Nanayakkara, J. Li et al., “Chronic intermittent hypoxia induces atherosclerosis,” American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 12, pp. 1290–1297, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. N. Halberg, T. Khan, M. E. Trujillo et al., “Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue,” Molecular & Cellular Biology, vol. 29, no. 16, pp. 4467–4483, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. L. F. Drager, Q. Yao, K. L. Hernandez et al., “Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4,” American Journal of Respiratory and Critical Care Medicine, vol. 188, no. 2, pp. 240–248, 2013. View at Publisher · View at Google Scholar · View at Scopus
  57. A. E. Serralde-Zúñiga, M. Guevara-Cruz, A. R. Tovar et al., “Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans,” Genes & Nutrition, vol. 9, no. 6, article 431, 2014. View at Publisher · View at Google Scholar · View at Scopus
  58. L. Dyugovskaya, A. Polyakov, P. Lavie, and L. Lavie, “Delayed neutrophil apoptosis in patients with sleep apnea,” American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 5, pp. 544–554, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. L. Dyugovskaya, A. Polyakov, V. Cohen-Kaplan, P. Lavie, and L. Lavie, “Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling,” Journal of Translational Medicine, vol. 10, no. 1, article 211, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. P.-F. Hu, D.-W. Lai, P.-L. Lu, J. Gao, and H. He, “ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells,” International Journal of Molecular Medicine, vol. 29, no. 4, pp. 613–618, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Takahashi, H. Okazaki, Y. Ogata, K. Takeuchi, U. Ikeda, and K. Shimada, “Lysophosphatidylcholine induces apoptosis in human endothelial cells through a p38-mitogen-activated protein kinase-dependent mechanism,” Atherosclerosis, vol. 161, no. 2, pp. 387–394, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. A. A. El Solh, M. E. Akinnusi, F. H. Baddoura, and C. R. Mankowski, “Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction,” American Journal of Respiratory & Critical Care Medicine, vol. 175, no. 11, pp. 1186–1191, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Jelic, D. J. Lederer, T. Adams et al., “Endothelial repair capacity and apoptosis are inversely related in obstructive sleep apnea,” Vascular Health and Risk Management, vol. 5, pp. 909–920, 2009. View at Google Scholar · View at Scopus
  64. A. S. M. Shamsuzzaman, B. J. Gersh, and V. K. Somers, “Obstructive sleep apnea: implications for cardiac and vascular disease,” The Journal of the American Medical Association, vol. 290, no. 14, pp. 1906–1914, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. I. Tuleta, C. N. França, D. Wenzel et al., “Hypoxia-induced endothelial dysfunction in apolipoprotein E-deficient mice; effects of infliximab and l-glutathione,” Atherosclerosis, vol. 236, no. 2, pp. 400–410, 2014. View at Publisher · View at Google Scholar
  66. M. de la Peña, A. Barceló, F. Barbe et al., “Endothelial function and circulating endothelial progenitor cells in patients with sleep apnea syndrome,” Respiration, vol. 76, no. 1, pp. 28–32, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. A. Ursavas, M. Karadağ, E. Rodoplu et al., “Circulating ICAM-1 and VCAM-1 levels in patients with obstructive sleep apnea syndrome,” Respiration, vol. 75, no. 5, pp. 525–532, 2007. View at Google Scholar
  68. G. Riccioni and V. Sblendorio, “Atherosclerosis: from biology to pharmacological treatment,” Journal of Geriatric Cardiology, vol. 9, no. 3, pp. 305–317, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. L. J. Olson, E. J. Olson, and V. K. Somers, “Obstructive sleep apnea and platelet activation: another potential link between sleep-disordered breathing and cardiovascular disease,” Chest, vol. 126, no. 2, pp. 339–341, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Rahangdale, S. Y. Yeh, V. Novack et al., “The influence of intermittent hypoxemia on platelet activation in obese patients with obstructive sleep apnea,” Journal of Clinical Sleep Medicine, vol. 7, no. 2, pp. 172–178, 2011. View at Google Scholar · View at Scopus
  71. T. Oga, K. Chin, A. Tabuchi et al., “Effects of obstructive sleep apnea with intermittent hypoxia on platelet aggregability,” Journal of Atherosclerosis and Thrombosis, vol. 16, no. 6, pp. 862–869, 2009. View at Google Scholar · View at Scopus
  72. L. Ayers, B. Ferry, S. Craig, D. Nicoll, J. R. Stradling, and M. Kohler, “Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea,” European Respiratory Journal, vol. 33, no. 3, pp. 574–580, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. I. C. Trombetta, C. Maki-Nunes, E. Toschi-Dias et al., “Obstructive sleep apnea is associated with increased chemoreflex sensitivity in patients with metabolic syndrome,” Sleep, vol. 36, no. 1, pp. 41–49, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. L. F. Man, G. L. Tipoe, and P. S. Leung, “Mechanisms of maladaptive responses of peripheral chemoreceptors to intermittent hypoxia in sleep-disordered breathing,” Acta Physiologica Sinica, vol. 66, no. 1, pp. 23–29, 2014. View at Google Scholar
  75. S.-Y. Lam, Y. Liu, K.-M. Ng et al., “Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways,” Histochemistry & Cell Biology, vol. 137, no. 3, pp. 303–317, 2012. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Tuomilehto, J. Seppä, and M. Uusitupa, “Obesity and obstructive sleep apnea—clinical significance of weight loss,” Sleep Medicine Reviews, vol. 17, no. 5, pp. 321–329, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. K. Cao, J. Xu, X. Zou et al., “Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice,” Free Radical Biology & Medicine, vol. 67, pp. 396–407, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. C.-X. Wu, Y. Liu, and J.-C. Zhang, “Chronic intermittent hypoxia and hypertension: a review of systemic inflammation and Chinese Medicine,” Chinese Journal of Integrative Medicine, vol. 19, no. 5, pp. 394–400, 2013. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. Liu and K.-J. Chen, “Atherosclerosis, vascular aging and therapeutic strategies,” Chinese Journal of Integrative Medicine, vol. 18, no. 2, pp. 83–87, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. Y. Liu, Y.-R. Jiang, J.-C. Zhang, and D. Z. Shi, “Integrative Chinese and western medicine on atherosclerosis of coronary heart disease: what are the new control strategies?” Chinese Science Bulletin, vol. 59, no. 11, pp. 1091–1096, 2014. View at Publisher · View at Google Scholar · View at Scopus