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01-09-2016 | Original Contribution

Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution

Authors: Sabine Ameling, Gourav Bhardwaj, Elke Hammer, Daniel Beug, Leif Steil, Yvonne Reinke, Kerstin Weitmann, Markus Grube, Christiane Trimpert, Karin Klingel, Reinhard Kandolf, Wolfgang Hoffmann, Matthias Nauck, Marcus Dörr, Klaus Empen, Stephan B. Felix, Uwe Völker

Published in: Basic Research in Cardiology | Issue 5/2016

Abstract

Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.

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Title: Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution
Authors: Sabine Ameling
Gourav Bhardwaj
Elke Hammer
Daniel Beug
Leif Steil
Yvonne Reinke
Kerstin Weitmann
Markus Grube
Christiane Trimpert
Karin Klingel
Reinhard Kandolf
Wolfgang Hoffmann
Matthias Nauck
Marcus Dörr
Klaus Empen
Stephan B. Felix
Uwe Völker
Publication date: 01-09-2016
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2016
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-016-0569-y

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