title: Endothelial Gata5 transcription factor regulates blood pressure.
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.
authors.affiliation: Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Smail
authors.initials: S
authors.lastname: Messaoudi
authors.affiliation: Kidney Research Center, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Kidney Research Center, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Alex
authors.initials: A
authors.lastname: Gutsol
authors.affiliation: Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wight
authors.affiliation: Kidney Research Center, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hébert
authors.affiliation: University of Ottawa Heart Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Ragnar O
authors.initials: RO
authors.lastname: Vilmundarson
authors.affiliation: Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Makrigiannis
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, 900 rue St-Denis, Montréal, Québec, Canada H2X 0A9.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.affiliation: University of Ottawa Heart Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
authors.affiliation: University of Ottawa Heart Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.affiliation: University of Ottawa Heart Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Alexandre F R
authors.initials: AFR
authors.lastname: Stewart
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G128TA, UK.
authors.forename: Rhian M
authors.identifier: http://orcid.org/0000-0003-0670-0887
authors.initials: RM
authors.lastname: Touyz
authors.affiliation: Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H8M5.
authors.forename: Mona
authors.initials: M
authors.lastname: Nemer
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D050992:GATA5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human; C494756:Gata5 protein, mouse