Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Effect of Nocturnal Hemodialysis (NHD) on Cardiomyocyte Gene Expression

ABSTRACT: Frequent hemodialysis is associated with improvement in myocardial mechanics and cardiac gene expression profile Uremic plasma (10%) before and after NHD was added to cultures of Neonatal Sprague-Dawley rat ventricular myocytes

ORGANISM(S): Rattus norvegicus

SUBMITTER: Sara Arab

PROVIDER: E-GEOD-28723 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Impact of frequent nocturnal hemodialysis on myocardial mechanics and cardiomyocyte gene expression.

Chan Christopher T CT Arab Sara S Carasso Shemy S Moravsky Gil G Li Guo Hua GH Liu Peter P PP Rakowski Harry H

Circulation. Cardiovascular imaging 20120530 4

<h4>Background</h4>Regression of left ventricular mass with nocturnal hemodialysis has been observed. The influence of nocturnal hemodialysis on myocardial mechanics and cardiomyocyte gene expression is unknown.<h4>Methods and results</h4>Forty-two patients (30 male:12 female; age, 44 ± 12 years [mean ± SD]) with end-stage renal disease were followed for 3.1 ± 1.8 years before and after conversion to nocturnal hemodialysis and were compared with 29 normal subjects (18 male:11 female; age, 48 ± 1 ...[more]

PMID: 22647434

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Project description:Background. Chronic renal failure is characterized by progressive renal scarring and accelerated cardiovascular disease. In animal models, this is thought to be due to non-dialyzable uremic toxins M-bM-^@M-^S small, protein-bound molecules normally secreted via Organic Anion Transporters (OATs) in the proximal renal tubule,rather than filtered at the glomerulus. The best studied of these is indoxyl sulfate (IS). Methods. We examined global gene expression responses in cultured normal human renal tubular cells incubated with control plasma (n=5) or pre- and post-dialysis uremic plasma (n=10). Results. GeneSpring analysis of microarrays revealed significantly altered expression of 2016 genes. The expression of 537 genes M-bM-^@M-^\normalizedM-bM-^@M-^] in post-dialysis plasma, suggesting removal of M-bM-^@M-^\low molecular weight uremic toxinsM-bM-^@M-^] by dialysis. The expression of the majority of dysregulated genes (1479) was not normalized in post-dialysis plasma. These likely represent the effects of substances not effectively removed by dialysis (M-bM-^@M-^\protein-bound uremic toxinsM-bM-^@M-^]). Addition of indoxyl sulfateto control plasma simulated most effects (81.1%) of uremic plasma, while the addition of probenecid, an OAT inhibitor, to uremic plasma reversed most changes in gene expression. Analysis of molecular programs with the Gene Set Enrichment Analysis and the DAVID database revealed patterns common to indoxyl sulfate-treated control plasma, pre-dialysis, and post-dialysis uremic plasma. These included increased cell cycle, pro-inflammatory, and pro-fibrotic molecular programs, particularly genes in the TGF-M-NM-2 pathway. Conclusion: These findings provide insight into the role of non-dialyzable, protein-bound uremic toxins in the pathogenesis of renal scarring and uremic vasculopathy. The GSEA patterns confirm that inflammatory and fibrotic programs are active. Transcriptomic remodeling in response to external stimulus RNA from non-immortalized cultured renal cortical cells incubated with plasma samples from 5 controls, 10 uremics pre-dialysis, 10 uremics post-dialysis, 5 controls with indoxyl sulfate added, 5 uremics pre-dialysis with probenecid added, 5 uremics post-dialysis with indoxyl sulfate added

Dataset Information

Effect of Nocturnal Hemodialysis (NHD) on Cardiomyocyte Gene Expression

Publications

Impact of frequent nocturnal hemodialysis on myocardial mechanics and cardiomyocyte gene expression.

Similar Datasets

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