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Endothelial Gata5 transcription factor regulates blood pressure

Author

Listed:
  • Smail Messaoudi

    (Faculty of Medicine, Microbiology and Immunology, University of Ottawa)

  • Ying He

    (Kidney Research Center, University of Ottawa)

  • Alex Gutsol

    (Kidney Research Center, University of Ottawa)

  • Andrew Wight

    (Faculty of Medicine, Microbiology and Immunology, University of Ottawa)

  • Richard L. Hébert

    (Kidney Research Center, University of Ottawa)

  • Ragnar O. Vilmundarson

    (University of Ottawa Heart Institute, University of Ottawa)

  • Andrew P. Makrigiannis

    (Faculty of Medicine, Microbiology and Immunology, University of Ottawa)

  • John Chalmers

    (The George Institute for Global Health, The University of Sydney, The Royal Prince Alfred Hospital)

  • Pavel Hamet

    (Centre de Recherche du Centre Hospitalier de l’Université de Montréal)

  • Johanne Tremblay

    (University of Ottawa Heart Institute, University of Ottawa)

  • Ruth McPherson

    (University of Ottawa Heart Institute, University of Ottawa)

  • Alexandre F. R. Stewart

    (University of Ottawa Heart Institute, University of Ottawa)

  • Rhian M. Touyz

    (Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow)

  • Mona Nemer

    (Faculty of Medicine, Microbiology and Immunology, University of Ottawa)

Abstract

Despite its high prevalence and economic burden, the aetiology of human hypertension remains incompletely understood. Here we identify the transcription factor GATA5, as a new regulator of blood pressure (BP). GATA5 is expressed in microvascular endothelial cells and its genetic inactivation in mice (Gata5-null) leads to vascular endothelial dysfunction and hypertension. Endothelial-specific inactivation of Gata5 mimics the hypertensive phenotype of the Gata5-null mice, suggestive of an important role for GATA5 in endothelial homeostasis. Transcriptomic analysis of human microvascular endothelial cells with GATA5 knockdown reveals that GATA5 affects several genes and pathways critical for proper endothelial function, such as PKA and nitric oxide pathways. Consistent with a role in human hypertension, we report genetic association of variants at the GATA5 locus with hypertension traits in two large independent cohorts. Our results unveil an unsuspected link between GATA5 and a prominent human condition, and provide a new animal model for hypertension.

Suggested Citation

  • Smail Messaoudi & Ying He & Alex Gutsol & Andrew Wight & Richard L. Hébert & Ragnar O. Vilmundarson & Andrew P. Makrigiannis & John Chalmers & Pavel Hamet & Johanne Tremblay & Ruth McPherson & Alexand, 2015. "Endothelial Gata5 transcription factor regulates blood pressure," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9835
    DOI: 10.1038/ncomms9835
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