Gene expression and microrna expression analysis in small arteries of spontaneously hypertensive rats. Evidence for er stress
Entity
UAM. Departamento de FisiologíaPublisher
Public Library of ScienceDate
2015-09-10Citation
10.1371/journal.pone.0137027
PLos ONE 10.9 (2015): e0137027
ISSN
1932-6203DOI
10.1371/journal.pone.0137027Funded by
This work was supported by the European Union, Marie Curie ITN number 606998 and 235711Project
info:eu-repo/grantAgreement/EC/FP7/606998; info:eu-repo/grantAgreement/EC/FP7/235711Editor's Version
http://dx.doi.org/10.1371/journal.pone.0137027Subjects
MicroRNA; Arteries; Stress; Hypertension; MedicinaRights
© 2015 Palao et alAbstract
Small arteries are known to develop functional and structural alterations in hypertension.
However, the mechanisms of this remodeling are not fully understood.We hypothesized
that altered gene expression is associated with the development of hypertension in mesenteric
arteries of spontaneously hypertensive rats (SHR). Three sublines of SHR and normotensive
Wistar Kyoto rats (WKY) were studied at 6 weeks and 5 months of age. MiRNA and
mRNA microarray experiments were performed and analyzed with bioinformatical tools,
including Ingenuity Pathway Analysis (IPA). Principal component analysis showed a clear
separation in both miRNA and mRNA expression levels between both ages studied, demonstrating
strong age-related changes in expression. At the miRNA level, IPA identified differences
between SHR and WKY related to metabolic diseases, cellular growth, and
proliferation. The mRNAs differentially expressed between SHR and WKY were related to
metabolism, cellular movement and proliferation. The most strongly upregulated gene (9.2-
fold) was thrombospondin 4 (Thbs4), a protein involved in the endoplasmic reticulum (ER)
stress response that activates transcription factor 6α (ATF6α). ATF6α downstream targets
were also differentially expressed in SHR vs. WKY. Differential expression of THBS4, the
cleaved form of ATF6α, and two of its targets were further confirmed at the protein level by
western blot. In summary, these data revealed a number of genes (n = 202) and miRNAs
(n = 3) in mesenteric arteries of SHR that had not been related to hypertension previously.
The most prominent of these, Thbs4, is related to vascular ER stress that is associated with
hypertension
Files in this item
Google Scholar:Palao, Teresa
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Swärd, Karl
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Jongejan, Aldo
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Moerland, Perry D.
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De Vos, Judith
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Van Weert, Angela
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Arribas Rodríguez, Silvia Magdalena
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Groma, Gergely
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Van Bavel, Ed
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Bakker, Erik N T P
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