Journal article
Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution
Basic research in cardiology, Vol.111(5), 53
09/2016
DOI: 10.1007/s00395-016-0569-y
PMCID: PMC7101709
PMID: 27412778
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.
Details
- Title: Subtitle
- Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution
- Creators
- Sabine Ameling - DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, GermanyGourav Bhardwaj - Universitätsmedizin GreifswaldElke Hammer - Universitätsmedizin GreifswaldDaniel Beug - Universitätsmedizin GreifswaldLeif Steil - Universitätsmedizin GreifswaldYvonne Reinke - Universitätsmedizin GreifswaldKerstin Weitmann - Universitätsmedizin GreifswaldMarkus Grube - Universitätsmedizin GreifswaldChristiane Trimpert - Universitätsmedizin GreifswaldKarin Klingel - University of TübingenReinhard Kandolf - University Hospital TübingenWolfgang Hoffmann - Universitätsmedizin GreifswaldMatthias Nauck - Universitätsmedizin GreifswaldMarcus Dörr - Universitätsmedizin GreifswaldKlaus Empen - Universitätsmedizin GreifswaldStephan B Felix - Universitätsmedizin GreifswaldUwe Völker - Universitätsmedizin Greifswald
- Resource Type
- Journal article
- Publication Details
- Basic research in cardiology, Vol.111(5), 53
- DOI
- 10.1007/s00395-016-0569-y
- PMID
- 27412778
- PMCID
- PMC7101709
- ISSN
- 0300-8428
- eISSN
- 1435-1803
- Language
- English
- Date published
- 09/2016
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984360044902771
Metrics
9 Record Views