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Mutation of the von Hippel-Lindau Gene Alters Human Cardiopulmonary Physiology

  • T. G. Smith
  • J. T. Brooks
  • G. M. Balanos
  • T. R. Lappin
  • D. M. Layton
  • D. L. Leedham
  • C. Liu
  • P. H. Maxwell
  • M. F. McMullin
  • C. J. McNamara
  • M. J. Percy
  • C. W. Pugh
  • P. J. Ratcliffe
  • N. P. Talbot
  • M. Treacy
  • P. A. Robbins
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 605)

Intracellular responses to hypoxia are coordinated by the von Hippel- Lindau — hypoxia-inducible factor (VHL-HIF) transcriptional system. This study investigated the potential role of the VHL-HIF pathway in human systems-level physiology. Patients diagnosed with Chuvash polycythaemia, a rare disorder in which VHL signalling is specifically impaired, were studied during acute hypoxia and hypercapnia. Subjects breathed through a mouthpiece and ventilation was measured while pulmonary vascular tone was assessed echocardiographically. The patients were found to have elevated basal ventilation and pulmonary vascular tone, and ventilatory, pulmonary vasoconstrictive and heart rate responses to acute hypoxia were greatly increased, as were heart rate responses to hypercapnia. The patients also had abnormal pulmonary function on spirometry. This study's findings demonstrate that the VHL-HIF signalling pathway, which is so central to intracellular oxygen sensing, also regulates the organ systems upon which cellular oxygen delivery ultimately depends.

Keywords

Atrial Natriuretic Peptide Normal Control Group Heart Rate Response Peak Expiratory Flow Rate Acute Hypoxia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • T. G. Smith
  • J. T. Brooks
  • G. M. Balanos
  • T. R. Lappin
  • D. M. Layton
  • D. L. Leedham
  • C. Liu
  • P. H. Maxwell
  • M. F. McMullin
  • C. J. McNamara
  • M. J. Percy
  • C. W. Pugh
  • P. J. Ratcliffe
  • N. P. Talbot
  • M. Treacy
  • P. A. Robbins

There are no affiliations available

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