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HIF isoforms in the skin differentially regulate systemic arterial pressure.

Andrew S Cowburn1, Norihiko Takeda, Adam T Boutin

  • 1Departments of Physiology, Development and Neuroscience and Medicine, University of Cambridge CB2 3EG, Cambridge, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|October 9, 2013
PubMed
Summary

The balance between hypoxia-inducible factor (HIF)-1α and HIF-2α in skin cells is crucial for regulating blood flow and blood pressure. This balance impacts thermal adaptation and exercise capacity, with implications for hypertension.

Keywords:
HIF-alphaarginasevascular tone

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Area of Science:

  • Physiology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Tissue perfusion and oxygenation are vital and rely on homeostatic mechanisms controlling vascular flow.
  • Localized control of tissue blood flow, known as autoregulation, is a critical component of these mechanisms.

Purpose of the Study:

  • To investigate the role of hypoxia-inducible factor (HIF) transcription factor isoforms, specifically HIF-1α and HIF-2α, in regulating local and systemic blood flow.
  • To examine the impact of HIF isoform balance in keratinocytes on physiological functions and blood pressure.
  • To explore the potential link between HIF isoform levels and human hypertension.

Main Methods:

  • Utilized keratinocyte-specific mutant mice to study the effects of altered HIF isoform balance.
  • Assessed impacts on thermal adaptation, exercise capacity, and systemic arterial pressure.
  • Investigated the relationship between HIF isoform regulation, nitric oxide production, and blood flow.
  • Correlated altered HIF isoform levels in human skin with idiopathic hypertension.

Main Results:

  • The net balance between HIF-1α and HIF-2α is essential for regulating both local and systemic blood flow in mouse skin.
  • Imbalanced HIF isoforms in keratinocytes affect thermal adaptation, exercise capacity, and systemic arterial pressure.
  • Opposing actions of HIF-1α and HIF-2α are linked to their regulation of nitric oxide production.
  • A correlation was observed between altered skin HIF isoform levels and the severity of idiopathic hypertension in humans.

Conclusions:

  • The balance of HIF-1α and HIF-2α expression in keratinocytes is a key regulator of tissue perfusion and systemic arterial pressure.
  • These findings suggest a novel mechanism controlling blood flow and blood pressure with potential implications for understanding and treating human hypertension.