Endothelial Gata5 transcription factor regulates blood pressure

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; Alexandre F.R. Stewart; Rhian M. Touyz; Mona Nemer

doi:10.1038/ncomms9835

Endothelial Gata5 transcription factor regulates blood pressure

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, Alexandre F.R. Stewart, Rhian M. Touyz, Mona Nemer

Résultat de recherche: Article › examen par les pairs

39 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Numéro d'article	8835
Journal	Nature Communications
Volume	6
DOI	https://doi.org/10.1038/ncomms9835
Statut de publication	Published - nov. 30 2015
Publié à l'externe	Oui

Note bibliographique

Funding Information:
We are grateful to Drs Chris Kennedy and Dylan Burger for advice and reagents and to Megan Fortier, Janie Beauregard, Carole Long, Mounsif Haloui and the uOttawa Histology Core for Technical Support. We thank Franc¸ois-Christophe Blanchet-Marois and Franc¸ois Harvey for bioinformatics analyses and John Raelson for statistical analysis. The members of the genetic sub-study of ADVANCE, Stephen Harrap and Michel Marre are also acknowledged. This work was supported by grants from the Canadian Institute of Health Research (CIHR). The genetic epidemiological work of ADVANCE sub-study was funded by Prognomix Inc. and grants from Genome Quebec and CIHR. The clinical study was managed by the George Institute for international Health (Sydney, Australia) with grants received from Les Laboratoires Servier, France and from the Medical Research Council of Australia.

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

Accès au document

10.1038/ncomms9835

Autres fichiers et liens

Citer

@article{3b0e58562fce4d16917849df36a0a460,

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.",

author = "Smail Messaoudi and Ying He and Alex Gutsol and Andrew Wight and H{\'e}bert, {Richard L.} and Vilmundarson, {Ragnar O.} and Makrigiannis, {Andrew P.} and John Chalmers and Pavel Hamet and Johanne Tremblay and Ruth McPherson and Stewart, {Alexandre F.R.} and Touyz, {Rhian M.} and Mona Nemer",

note = "Funding Information: We are grateful to Drs Chris Kennedy and Dylan Burger for advice and reagents and to Megan Fortier, Janie Beauregard, Carole Long, Mounsif Haloui and the uOttawa Histology Core for Technical Support. We thank Franc¸ois-Christophe Blanchet-Marois and Franc¸ois Harvey for bioinformatics analyses and John Raelson for statistical analysis. The members of the genetic sub-study of ADVANCE, Stephen Harrap and Michel Marre are also acknowledged. This work was supported by grants from the Canadian Institute of Health Research (CIHR). The genetic epidemiological work of ADVANCE sub-study was funded by Prognomix Inc. and grants from Genome Quebec and CIHR. The clinical study was managed by the George Institute for international Health (Sydney, Australia) with grants received from Les Laboratoires Servier, France and from the Medical Research Council of Australia.",

year = "2015",

month = nov,

day = "30",

doi = "10.1038/ncomms9835",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Endothelial Gata5 transcription factor regulates blood pressure

AU - Messaoudi, Smail

AU - He, Ying

AU - Gutsol, Alex

AU - Wight, Andrew

AU - Hébert, Richard L.

AU - Vilmundarson, Ragnar O.

AU - Makrigiannis, Andrew P.

AU - Chalmers, John

AU - Hamet, Pavel

AU - Tremblay, Johanne

AU - McPherson, Ruth

AU - Stewart, Alexandre F.R.

AU - Touyz, Rhian M.

AU - Nemer, Mona

N1 - Funding Information: We are grateful to Drs Chris Kennedy and Dylan Burger for advice and reagents and to Megan Fortier, Janie Beauregard, Carole Long, Mounsif Haloui and the uOttawa Histology Core for Technical Support. We thank Franc¸ois-Christophe Blanchet-Marois and Franc¸ois Harvey for bioinformatics analyses and John Raelson for statistical analysis. The members of the genetic sub-study of ADVANCE, Stephen Harrap and Michel Marre are also acknowledged. This work was supported by grants from the Canadian Institute of Health Research (CIHR). The genetic epidemiological work of ADVANCE sub-study was funded by Prognomix Inc. and grants from Genome Quebec and CIHR. The clinical study was managed by the George Institute for international Health (Sydney, Australia) with grants received from Les Laboratoires Servier, France and from the Medical Research Council of Australia.

PY - 2015/11/30

Y1 - 2015/11/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84948809067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948809067&partnerID=8YFLogxK

U2 - 10.1038/ncomms9835

DO - 10.1038/ncomms9835

M3 - Article

C2 - 26617239

AN - SCOPUS:84948809067

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 8835

ER -

Endothelial Gata5 transcription factor regulates blood pressure

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

Accès au document

Autres fichiers et liens

Empreinte numérique

Citer