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Oxygen-Sensitive Transcription Factors and Hypoxia-Mediated Pulmonary Hypertension

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Textbook of Pulmonary Vascular Disease

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Abstract

Dynamic changes in oxygen partial pressure (pO2) constitute a potential signaling mechanism for the regulation of expression and activation of oxygen-responsive transcription factors. Hypoxia might affect tissues or even the whole body: defective oxygen uptake in the lung, impaired oxygen transport capacity in the blood, or lower pO2 in the environment, as experienced at high altitude. The reaction to this potentially life-threatening situation requires hypoxia-dependent gene regulation that induces a variety of specific adaptation mechanisms that ensure survival at cellular and systemic levels alike. Once exposed to hypoxia, the pulmonary and systemic vasculature, and potentially also the airway chemoreceptors, enables a corresponding response within seconds; changes in gene expression on the other hand require minutes to hours. To mediate these adaptive effects a range of oxygen-sensitive transcription factors play important roles. An adaptive response of the pulmonary circulation to low oxygen tension is the increase in pulmonary pressure. This is a self-regulatory mechanism for maintaining the optimal balance between ventilation and perfusion. During acute hypoxia, the vasoconstriction acts to reduce the perfusion of underventilated parts of the lungs and instead divert blood to well-ventilated regions, meaning that the acute response is mainly associated with a change in vascular tone. Chronic hypoxia and the resulting endothelial dysfunction, on the other hand, are associated with sustained pulmonary hypertension. This is a serious condition characterized by elevation in pulmonary arterial pressure. A constant elevation in pulmonary arterial pressure will lead to right ventricular hypertrophy and ultimately right ventricular failure and possibly death.

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Authors and Affiliations

  1. Institute of Veterinary Physiology, Vetsuisse-Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthrurerstrasse 260, 8057, Zurich, Switzerland

    Max Gassmann

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  1. Louise Østergaard
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  2. Vinzenz H. Schmid
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  3. Max Gassmann
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Correspondence to Max Gassmann .

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Editors and Affiliations

  1. Departments of Medicine, COMRB Rm. 3131 (MC 719), University of Illinois at Chicago, 909 South Wolcott Avenue, Chicago, 60612, Illinois, USA

    Jason X. -J. Yuan

  2. 310 Admin.Office Building (MC 672), University of Illinois at Chicago, 1737 W. Polk Street, Suite 310, Chicago, 60612, Illinois, USA

    Joe G.N. Garcia

  3. Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093-0623, California, USA

    John B. West

  4. Dept. Pulmonary & Critical Care Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, Massachusetts, USA

    Charles A. Hales

  5. Department of Medicine, University of Chicago Medical Center, 5841 S. Maryland Ave., Chicago, 60637, Illinois, USA

    Stuart Rich

  6. Department of Medicine, University of Chicago School of Medicine, 5841 S. Maryland Ave., Chicago, 60637, Illinois, USA

    Stephen L. Archer

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Østergaard, L., Schmid, V.H., Gassmann, M. (2011). Oxygen-Sensitive Transcription Factors and Hypoxia-Mediated Pulmonary Hypertension. In: Yuan, JJ., Garcia, J., West, J., Hales, C., Rich, S., Archer, S. (eds) Textbook of Pulmonary Vascular Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-87429-6_49

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