Mutation of the von Hippel-Lindau gene alters human cardiopulmonary physiology

Thomas 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

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15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)51-6
Number of pages6
JournalAdvances in Experimental Medicine And Biology
Publication statusPublished - 2008


  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Carbon Dioxide/blood
  • Forced Expiratory Volume
  • Heart/physiopathology
  • Humans
  • Hypercapnia/genetics
  • Hypoxia/genetics
  • Mutation
  • Polycythemia/genetics
  • Reference Values
  • Respiratory Function Tests
  • Respiratory Physiological Phenomena
  • Signal Transduction
  • Von Hippel-Lindau Tumor Suppressor Protein/genetics


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