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Cardiac transcriptome profiles of S.LEW congenic strain compared with the hypertensive Dahl S rat

ABSTRACT: Despite inheritance of hypertension in families, identifying genetic mechanisms predisposing individuals to hypertension has remained challenging. The effects of single genes contributing to the development of hypertension may not be readily detected in individuals whose genomes also contain other genetic factors that resist hypertension. By using a highly permissive rat genome for inherited hypertension, we demonstrate that increased expression of one such gene, Rififylin (Rffl), is a novel inherited risk factor for hypertension and increased mortality. Animals overexpressing Rffl demonstrated delayed endocytic recycling, accumulated polyubiquitinated proteins, increased beats/min of neonatal cardiomyocytes, had shorter QT-intervals and developed salt-insensitive hypertension very early in their life (50-52 days). Thus, the discovery of a physiological link between overexpression of rififylin and the development of hypertension constitutes a novel mechanism that could be targeted for rectifying normal QT-interval and preventing hypertension.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE23643 | GEO | 2011/01/20

SECONDARY ACCESSION(S): PRJNA130955

REPOSITORIES: GEO

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Cardiac transcriptome profiles of S.LEW congenic strain compared with the hypertensive Dahl S rat

Project description:Despite inheritance of hypertension in families, identifying genetic mechanisms predisposing individuals to hypertension has remained challenging. The effects of single genes contributing to the development of hypertension may not be readily detected in individuals whose genomes also contain other genetic factors that resist hypertension. By using a highly permissive rat genome for inherited hypertension, we demonstrate that increased expression of one such gene, Rififylin (Rffl), is a novel inherited risk factor for hypertension and increased mortality. Animals overexpressing Rffl demonstrated delayed endocytic recycling, accumulated polyubiquitinated proteins, increased beats/min of neonatal cardiomyocytes, had shorter QT-intervals and developed salt-insensitive hypertension very early in their life (50-52 days). Thus, the discovery of a physiological link between overexpression of rififylin and the development of hypertension constitutes a novel mechanism that could be targeted for rectifying normal QT-interval and preventing hypertension. Six male S control and 6 male congenic S.LEW(10)x12x2x3x5 rats born on the same day were selected, weaned at 30 days of age, and caged with 1 congenic and 1 S rat per cage. They were raised on a low-salt (0.3%) diet (Harlan Teklad diet TD 7034; Harlan–Sprague-Dawley) and sacrificed at 53 days of age and total RNAs were isolated from the heart. The isolated RNA from two animals were pooled together and considered as one biological sample. Three such RNA samples from S and congenic rats were used for the cRNA preparation. cRNA was prepared and fragmented as suggested by Affymetrix technical manual, and simultaneously hybridized (15 µg adjusted cRNA for each chip) to Rat Expression Array 230 2.0 (3' IVT Expression Analysis). Statistical analyses of the microarray data were performed with BH adjustment using R statistical package (version 2.8.1).

2011-01-20 | E-GEOD-23643 | biostudies-arrayexpress

Comparison of renal transcript levels in Dahl Salt-sensitive (S) rat with S.R congenic rat containing a BP QTL

Project description:Kidney samples from three Dahl Salt-sensitive S rats were compared with kidney samples from three S.R(9)x3A congenic rats. Keywords = Blood Pressure Keywords = Quantitative trait locus Keywords = QTL Keywords = hypertension Keywords = rat Keywords = congenic Keywords: parallel sample

2004-09-20 | GSE1775 | GEO

Insights into Dahl salt-sensitive hypertension revealed

2005-11-17 | GSE3588 | GEO

Phosphoproteomic analysis of the Dahl sensitive rat

Project description:We analyzed the glomerular proteome in Dahl salt sensitive rats after 21 days of induction of hypertension, after 7 days and in control conditions.

2019-11-20 | PXD007937 | Pride

Hypertension state and overweight/obesity affect the transcriptome alternation in Human Visceral Adipose Tissue

Project description:In order to explore the effect of hypertension and overweight/obesity on human visceral adipose tissue transcriptome, we collected three visceral adipose tissue samples from normal weight individuals (non hypertension), overweight/obese individuals (non hypertension) and overweight/obese individuals with hypertension, and sequenced their transcriptome.

2023-07-03 | GSE217007 | GEO

Insights into Dahl salt-sensitive hypertension revealed

Project description:The results of this study identified a number of pathways potentially important for the amelioration of hypertension and renal injury in SS-13BN/Mcw rats, and these results generated a series of testable hypotheses related to the role of the renal medulla in the complex mechanism of salt-sensitive hypertension. Rats were paired for microarray hybridization, and the results were analyzed. Each of the four between-group comparisons comprised three pairs of rats examined by six microarrays with dye switching for each pair. Dye switching was not necessary for within-group comparisons, because the two rats of each pair were equivalent in terms of their treatment status. The expression data from the present study were combined with those from 24 microarrays hybridized in our previous study and used to identify genes exhibiting the most distinct temporal patterns of expression between SS and SS-13BN/Mcw over the time course studied.

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Dietary Salt effects on Renal Expression of Dahl SS/Jr (S) and Congenic Rats

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-08-28 | GSE29078 | GEO

Transcriptomic Analysis in Renal T Lymphocytes Exposes Sodium-Independent Dietary Differences in Dahl Salt-Sensitive Rats

Project description:Background. The Dahl salt-sensitive (SS) rat is an established model of salt-sensitive hypertension and renal damage. Recently, sodium-independent dietary effects were shown to be important in the development of the SS hypertensive phenotype. Compared to Dahl SS/JrHsdMcwi (SS/MCW) rats fed a purified diet (AIN-76A), grain-fed Dahl SS/JrHsdMcwiCrl rats (SS/CRL; Teklad 5L2F) were less susceptible to salt-induced hypertension and renal damage. Methods. With the known role of the immune system in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys. To further identify distinct molecular pathways between SS/MCW and SS/CRL, transcriptomic analysis was performed via RNA sequencing in T-cells isolated from the blood and kidneys of low and high salt-fed rats. Results. Following a 3-week high salt (4.0% NaCl) challenge, SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 vs 141.9±14.4 mmHg) and albuminuria (21.7±3.5 vs 162.9±22.2 mg/day) compared to SS/MCW. Additionally, the absolute number of immune cells infiltrating the kidney was significantly reduced in SS/CRL. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney. Pathway analysis of significant differentially expressed genes between SS/MCW and SS/CRL renal and circulating T-cells demonstrated salt-induced changes in genes related to inflammation in SS/MCW compared to metabolism-related pathways in SS/CRL. Conclusions. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that sodium-independent dietary effects may influence the immune response and infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.

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Project description:Kidney samples from three Dahl Salt-sensitive S rats were compared with kidney samples from three S.R(9)x3A congenic rats.

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Effects of potassium supplementation and depletion in the development of salt-sensitive hypertension in male and female rats

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2024-02-24 | GSE255582 | GEO

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