Limits...
Massive analysis of cDNA Ends (MACE) and miRNA expression profiling identifies proatherogenic pathways in chronic kidney disease.

Zawada AM, Rogacev KS, Müller S, Rotter B, Winter P, Fliser D, Heine GH - Epigenetics (2013)

Bottom Line: Formal interaction network analysis proved biological relevance of miRNA dysregulation, as 68 differentially expressed miRNAs could be connected to 47 reciprocally expressed target genes.Our study is the first comprehensive miRNA analysis in CKD that links dysregulated miRNA expression with differential expression of genes connected to inflammation and CVD.After recent animal data suggested that targeting miRNAs is beneficial in experimental CVD, our data may now spur further research in the field of CKD-associated human CVD.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine IV; Saarland University Medical Center; Homburg, Germany.

ABSTRACT
Epigenetic dysregulation contributes to the high cardiovascular disease burden in chronic kidney disease (CKD) patients. Although microRNAs (miRNAs) are central epigenetic regulators, which substantially affect the development and progression of cardiovascular disease (CVD), no data on miRNA dysregulation in CKD-associated CVD are available until now. We now performed high-throughput miRNA sequencing of peripheral blood mononuclear cells from ten clinically stable hemodialysis (HD) patients and ten healthy controls, which allowed us to identify 182 differentially expressed miRNAs (e.g., miR-21, miR-26b, miR-146b, miR-155). To test biological relevance, we aimed to connect miRNA dysregulation to differential gene expression. Genome-wide gene expression profiling by MACE (Massive Analysis of cDNA Ends) identified 80 genes to be differentially expressed between HD patients and controls, which could be linked to cardiovascular disease (e.g., KLF6, DUSP6, KLF4), to infection / immune disease (e.g., ZFP36, SOCS3, JUND), and to distinct proatherogenic pathways such as the Toll-like receptor signaling pathway (e.g., IL1B, MYD88, TICAM2), the MAPK signaling pathway (e.g., DUSP1, FOS, HSPA1A), and the chemokine signaling pathway (e.g., RHOA, PAK1, CXCL5). Formal interaction network analysis proved biological relevance of miRNA dysregulation, as 68 differentially expressed miRNAs could be connected to 47 reciprocally expressed target genes. Our study is the first comprehensive miRNA analysis in CKD that links dysregulated miRNA expression with differential expression of genes connected to inflammation and CVD. After recent animal data suggested that targeting miRNAs is beneficial in experimental CVD, our data may now spur further research in the field of CKD-associated human CVD.

Show MeSH

Related in: MedlinePlus

Figure 2. Differences in gene expression between control subjects and hemodialysis patients. An MA plot was created to visualize the relation between log2 fold-change between controls and hemodialysis patients and log2 fold-average gene expression. Genes with a FDR (False Discovery Rate) adjusted P value < 0.05 are indicated in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928179&req=5

Figure 2: Figure 2. Differences in gene expression between control subjects and hemodialysis patients. An MA plot was created to visualize the relation between log2 fold-change between controls and hemodialysis patients and log2 fold-average gene expression. Genes with a FDR (False Discovery Rate) adjusted P value < 0.05 are indicated in red.

Mentions: The DESeq R/Bioconductor package was used to estimate the biological variance between replicates and to test for differential expression. We identified 80 differentially expressed genes (P < 0.05) in HD patients compared with healthy controls, of which 60 were upregulated and 20 were downregulated. Figure 2 visualizes differences in gene expression between HD patients and control subjects, whereas Table 1A and Table 1B list the top 15 upregulated as well as the top 15 downregulated genes in HD patients (based on their FDR [False Discovery Rate] adjusted P value, according to Benjamini and Hochberg21).


Massive analysis of cDNA Ends (MACE) and miRNA expression profiling identifies proatherogenic pathways in chronic kidney disease.

Zawada AM, Rogacev KS, Müller S, Rotter B, Winter P, Fliser D, Heine GH - Epigenetics (2013)

Figure 2. Differences in gene expression between control subjects and hemodialysis patients. An MA plot was created to visualize the relation between log2 fold-change between controls and hemodialysis patients and log2 fold-average gene expression. Genes with a FDR (False Discovery Rate) adjusted P value < 0.05 are indicated in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928179&req=5

Figure 2: Figure 2. Differences in gene expression between control subjects and hemodialysis patients. An MA plot was created to visualize the relation between log2 fold-change between controls and hemodialysis patients and log2 fold-average gene expression. Genes with a FDR (False Discovery Rate) adjusted P value < 0.05 are indicated in red.
Mentions: The DESeq R/Bioconductor package was used to estimate the biological variance between replicates and to test for differential expression. We identified 80 differentially expressed genes (P < 0.05) in HD patients compared with healthy controls, of which 60 were upregulated and 20 were downregulated. Figure 2 visualizes differences in gene expression between HD patients and control subjects, whereas Table 1A and Table 1B list the top 15 upregulated as well as the top 15 downregulated genes in HD patients (based on their FDR [False Discovery Rate] adjusted P value, according to Benjamini and Hochberg21).

Bottom Line: Formal interaction network analysis proved biological relevance of miRNA dysregulation, as 68 differentially expressed miRNAs could be connected to 47 reciprocally expressed target genes.Our study is the first comprehensive miRNA analysis in CKD that links dysregulated miRNA expression with differential expression of genes connected to inflammation and CVD.After recent animal data suggested that targeting miRNAs is beneficial in experimental CVD, our data may now spur further research in the field of CKD-associated human CVD.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine IV; Saarland University Medical Center; Homburg, Germany.

ABSTRACT
Epigenetic dysregulation contributes to the high cardiovascular disease burden in chronic kidney disease (CKD) patients. Although microRNAs (miRNAs) are central epigenetic regulators, which substantially affect the development and progression of cardiovascular disease (CVD), no data on miRNA dysregulation in CKD-associated CVD are available until now. We now performed high-throughput miRNA sequencing of peripheral blood mononuclear cells from ten clinically stable hemodialysis (HD) patients and ten healthy controls, which allowed us to identify 182 differentially expressed miRNAs (e.g., miR-21, miR-26b, miR-146b, miR-155). To test biological relevance, we aimed to connect miRNA dysregulation to differential gene expression. Genome-wide gene expression profiling by MACE (Massive Analysis of cDNA Ends) identified 80 genes to be differentially expressed between HD patients and controls, which could be linked to cardiovascular disease (e.g., KLF6, DUSP6, KLF4), to infection / immune disease (e.g., ZFP36, SOCS3, JUND), and to distinct proatherogenic pathways such as the Toll-like receptor signaling pathway (e.g., IL1B, MYD88, TICAM2), the MAPK signaling pathway (e.g., DUSP1, FOS, HSPA1A), and the chemokine signaling pathway (e.g., RHOA, PAK1, CXCL5). Formal interaction network analysis proved biological relevance of miRNA dysregulation, as 68 differentially expressed miRNAs could be connected to 47 reciprocally expressed target genes. Our study is the first comprehensive miRNA analysis in CKD that links dysregulated miRNA expression with differential expression of genes connected to inflammation and CVD. After recent animal data suggested that targeting miRNAs is beneficial in experimental CVD, our data may now spur further research in the field of CKD-associated human CVD.

Show MeSH
Related in: MedlinePlus