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Effects of Intermittent Hypoxia on Pulmonary Vascular and Systemic Diseases

Author

Listed:
  • Hiroshi Kimura

    (Department of Advanced Medicine for Pulmonary Circulation and Respiratory Failure, Graduate School of Medicine, Nippon Medical School, Bunkyo, Tokyo 113-8603, Japan)

  • Hiroyo Ota

    (Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan)

  • Yuya Kimura

    (Center for Pulmonary Diseases, NHO Tokyo National Hospital, Kiyose, Tokyo 204-0023, Japan)

  • Shin Takasawa

    (Department of Biochemistry, Nara Medical University, Kashihara, Nara 634-8521, Japan)

Abstract

Obstructive sleep apnea (OSA) causes many systemic disorders via mechanisms related to sympathetic nerve activation, systemic inflammation, and oxidative stress. OSA typically shows repeated sleep apnea followed by hyperventilation, which results in intermittent hypoxia (IH). IH is associated with an increase in sympathetic activity, which is a well-known pathophysiological mechanism in hypertension and insulin resistance. In this review, we show the basic and clinical significance of IH from the viewpoint of not only systemic regulatory mechanisms focusing on pulmonary circulation, but also cellular mechanisms causing lifestyle-related diseases. First, we demonstrate how IH influences pulmonary circulation to cause pulmonary hypertension during sleep in association with sleep state-specific change in OSA. We also clarify how nocturnal IH activates circulating monocytes to accelerate the infiltration ability to vascular wall in OSA. Finally, the effects of IH on insulin secretion and insulin resistance are elucidated by using an in vitro chamber system that can mimic and manipulate IH. The obtained data implies that glucose-induced insulin secretion (GIS) in pancreatic β cells is significantly attenuated by IH, and that IH increases selenoprotein P, which is one of the hepatokines, as well as TNF-α, CCL-2, and resistin, members of adipokines, to induce insulin resistance via direct cellular mechanisms. Clinical and experimental findings concerning IH give us productive new knowledge of how lifestyle-related diseases and pulmonary hypertension develop during sleep.

Suggested Citation

  • Hiroshi Kimura & Hiroyo Ota & Yuya Kimura & Shin Takasawa, 2019. "Effects of Intermittent Hypoxia on Pulmonary Vascular and Systemic Diseases," IJERPH, MDPI, vol. 16(17), pages 1-13, August.
    • Handle: RePEc:gam:jijerp:v:16:y:2019:i:17:p:3101-:d:261143
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    Citations

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    Cited by:

    1. Giuseppina Laganà & Nicolò Venza & Arianna Malara & Claudio Liguori & Paola Cozza & Calogera Pisano, 2021. "Obstructive Sleep Apnea, Palatal Morphology, and Aortic Dilatation in Marfan Syndrome Growing Subjects: A Retrospective Study," IJERPH, MDPI, vol. 18(6), pages 1-10, March.
    2. Chiara Stipa & Serena Incerti-Parenti & Matteo Cameli & Daniela Rita Ippolito & Antonio Gracco & Giulio Alessandri-Bonetti, 2023. "Antero-Posterior Mandibular Excursion in Obstructive Sleep Apnea Patients Treated with Mandibular Advancement Device: A Retrospective Cohort Study," IJERPH, MDPI, vol. 20(4), pages 1-9, February.
    3. Hai-Hua Chuang & Jen-Fu Hsu & Chao-Yung Wang & Li-Pang Chuang & Min-Chi Chen & Ning-Hung Chen & Yu-Shu Huang & Hsueh-Yu Li & Li-Ang Lee, 2021. "Hypertension in Children with Obstructive Sleep Apnea Syndrome—Age, Weight Status, and Disease Severity," IJERPH, MDPI, vol. 18(18), pages 1-17, September.
    4. Nicolò Venza & Giulia Alloisio & Magda Gioia & Claudio Liguori & Annarita Nappi & Carlotta Danesi & Giuseppina Laganà, 2022. "Saliva Analysis of pH and Antioxidant Capacity in Adult Obstructive Sleep Apnea Patients," IJERPH, MDPI, vol. 19(20), pages 1-7, October.

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