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Activation of Inflammatory Circulating Factors by Intermittent Hypoxia in Sleep Apnea Syndrome

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Intermittent Hypoxia and Human Diseases

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Abstract

Obstructive sleep apnea syndrome (OSAS), characterized by intermittent and recurrent pauses in respiration during sleep, constitutes an independent risk factor for cardiovascular morbidity. Intermittent hypoxia (IH) is the hallmark of OSAS. A large number of clinical studies, cell culture, and animal models utilizing IH delineate the central role of oxidative stress in OSAS. These facilitate increased interactions of blood leukocytes with endothelial cells, resulting in endothelial injury and dysfunction. Such events can promote the development of cardiovascular morbidities in OSAS. IH can activate several global signaling pathways and various transcription factors such as nuclear factor κB and hypoxia-inducible factor 1α, which play a key role in mediating the inflammatory and cardiovascular consequences in OSAS. This chapter summarized the current literature and our own data on phenotype, functional changes, and inflammatory responses of various blood cells exposed to IH in vivo and in vitro. We focus on the causal relationships between IH and atherogenic transformation of monocytes, lymphocytes, and neutrophils in OSAS patients and on the molecular mechanisms of the cell dysfunctions developed under IH conditions.

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Abbreviations

OSAS:

Obstructive sleep apnea syndrome

IH:

Intermittent hypoxia

nCPAP:

Nasal continuous positive air pressure

HIF:

Hypoxia-inducible factor

AHI:

Apnea-hypopnea index

ROS:

Reactive oxygen species

ECs:

Endothelial cells

EPO:

Erythropoietin

VEGF:

Vascular endothelial growth factor

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-regulated kinase

DCs:

Dendritic cells

Ox-LDL:

Oxidized low-density lipoprotein

PMA:

Phorbol myristate acetate

HUVEC:

Human umbilical vein endothelial cells

HCAEC:

Human coronary artery endothelial cells

NA:

Neutrophil apoptosis

IHD:

Ischemic heart disease

TNF:

Tumor necrotic factor

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Acknowledgments

We thank Prof. Peretz Lavie for his helpful comments and suggestions. We are also indebted to Prof. Lena Lavie for her constructive comments and criticism.

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  1. The Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Larissa Dyugovskaya & Andrey Polyakov

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  1. Larissa Dyugovskaya
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  2. Andrey Polyakov
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Correspondence to Larissa Dyugovskaya .

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  1. , Division of Cardiology, Virginia Commonwealth University, Richmond, 23298, Virginia, USA

    Lei Xi

  2. Bogomoletz Institute of Physiology, Kiev, 01601, Ukraine

    Tatiana V. Serebrovskaya

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Dyugovskaya, L., Polyakov, A. (2012). Activation of Inflammatory Circulating Factors by Intermittent Hypoxia in Sleep Apnea Syndrome. In: Xi, L., Serebrovskaya, T. (eds) Intermittent Hypoxia and Human Diseases. Springer, London. https://doi.org/10.1007/978-1-4471-2906-6_8

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