Endothelial Gata5 transcription factor regulates blood pressure

Messaoudi, S. et al. (2015) Endothelial Gata5 transcription factor regulates blood pressure. Nature Communications, 6, 8835. (doi: 10.1038/ncomms9835) (PMID:26617239) (PMCID:PMC4696516)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Messaoudi, S., He, Y., Gutsol, A., Wight, A., Hébert, R. L., Vilmundarson, R. O., Makrigiannis, A. P., Chalmers, J., Hamet, P., Tremblay, J., McPherson, R., Stewart, A. F. R., Touyz, R., and Nemer, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Communications
ISSN:2041-1723
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Nature Communications 6:8835
Publisher Policy:Reproduced under a Creative Commons License

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