TY  - JOUR
A1  - Zawada, Adam M.
A1  - Rogacev, Kyrill S.
A1  - Müller, Sören
A1  - Rotter, Björn
A1  - Winter, Peter
A1  - Fliser, Danilo
A1  - Heine, Gunnar H.
T1  - Massive analysis of cDNA Ends (MACE) and miRNA expression profiling identifies proatherogenic pathways in chronic kidney disease
T2  - Epigenetics
N2  - 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.
KW  - miRNA
KW  - epigenetics
KW  - kidney disease
KW  - hemodialysis
KW  - atherosclerosis
KW  - cardiovascular disease
KW  - MACE
KW  - next-generation sequencing
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37376
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373769
SN  - 1559-2294
SN  - 1559-2308
N1  - Copyright © 2014 Landes Bioscience. This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. Permission is granted subject to the terms of the License under which the work was published. Please check the License conditions for the work which you wish to reuse. Full and appropriate attribution must be given. This permission does not cover any third party copyrighted material which may appear in the work requested.
VL  - 9
IS  - 1
SP  - 161
EP  - 172
PB  - Landes Bioscience
CY  - Austin, Tex.
ER  -