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Nat Commun. 2015 Nov 30;6:8835. doi: 10.1038/ncomms9835.

Endothelial Gata5 transcription factor regulates blood pressure.

Author information

1
Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
2
Kidney Research Center, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
3
University of Ottawa Heart Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
4
The George Institute for Global Health, The University of Sydney, The Royal Prince Alfred Hospital, 83-117 Missenden Road, Camperdown, New South Wales 2050, Australia.
5
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, 900 rue St-Denis, Montréal, Québec, Canada H2X 0A9.
6
Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G128TA, UK.

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.

PMID:
26617239
PMCID:
PMC4696516
DOI:
10.1038/ncomms9835
[Indexed for MEDLINE]
Free PMC Article

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