Transcriptomics,Genomics

Dataset Information

39

Small artery remodeling depends on the genetic background in spontaneously hypertensive rats (mRNA)


ABSTRACT: Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that discrepant data in literature regarding the pathophysiology of vascular remodeling in hypertension result from the use of different rat sublines. Using micro-arrays, we studied miRNA and mRNA expression in resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Both WKY and SHR showed an age-related expression pattern that involved many genes related to the extracellular matrix. In SHR, this pattern was more extensive and included a specific increase in miR132-3p, and type III deiodinase. Direct comparison of WKY to SHR also yielded differences in expression, including thrombospondin 4. Heterogeneity in gene expression among sublines was associated with differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in vessels from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness. These results indicate that endothelial dysfunction, vascular stiffening, and inward remodeling of small arteries are not common features of hypertension, but are subline-dependent. Relatively minor differences in genetic background associate with different types of vascular remodeling in hypertensive rats. The clinical implication of this study is that more research into personalized treatment in hypertension is warranted. Overall design: 2x2 factorial design with 2 ages (6 weeks and 5 months) and 2 strains (WKY and SHR). For each strain 3 genetically different sublines were used. Per combination of conditions (age, strain, subline) one biological replicate was used (12) and for 4 a technical replicate was included (16 arrays in total). Each test sample consists of the mRNA pooled from the vessels of five animals. As common-reference an equimolar pool of all test samples used. SHR/NCrl, WKY/NCrl, and stroke-prone SHR (SHR/SP) rats were obtained from Charles River, the Netherlands. The SHR/NHsd and WKY/NHsd rats were derived from Harlan UK, (Bicester, U.K.) and bred at the local animal facility of the Universidad Autónoma de Madrid, Spain. WKY/NTac rats were obtained from Taconic Farms (Germantown, NY, USA).

INSTRUMENT(S): Agilent-028279 SurePrint G3 Rat GE 8x60K Microarray (Probe Name version)

SUBMITTER: Perry D Moerland  

PROVIDER: GSE53363 | GEO | 2015-10-02

SECONDARY ACCESSION(S): PRJNA231846

REPOSITORIES: GEO

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Publications

Gene Expression and MicroRNA Expression Analysis in Small Arteries of Spontaneously Hypertensive Rats. Evidence for ER Stress.

Palao Teresa T   Swärd Karl K   Jongejan Aldo A   Moerland Perry D PD   de Vos Judith J   van Weert Angela A   Arribas Silvia M SM   Groma Gergely G   vanBavel Ed E   Bakker Erik N T P EN  

PloS one 20150910 9


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  ...[more]

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