title: Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution.
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.
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Straße 15a, 17475, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ameling
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Straße 15a, 17475, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Gourav
authors.initials: G
authors.lastname: Bhardwaj
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Straße 15a, 17475, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beug
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Straße 15a, 17475, Greifswald, Germany.
authors.forename: Leif
authors.initials: L
authors.lastname: Steil
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Reinke
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Ellernholzstr. 1-2, 17487, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Weitmann
authors.affiliation: Department of Pharmacology, Centre of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, Felix-Hausdorff-Str. 3, 17487, Greifswald, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Grube
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Trimpert
authors.affiliation: Department of Molecular Pathology, University Hospital Tübingen, Liebermeisterstr. 8, 72076, Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.affiliation: Department of Molecular Pathology, University Hospital Tübingen, Liebermeisterstr. 8, 72076, Tübingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Ellernholzstr. 1-2, 17487, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoffmann
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dörr
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Empen
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. felix@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany. felix@uni-greifswald.de.
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Straße 15a, 17475, Greifswald, Germany. voelker@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany. voelker@uni-greifswald.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007163:Immunosorbent Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D040901:Proteomics; D059467:Transcriptome
chemical_list: D007074:Immunoglobulin G
keywords: Cardiomyopathy; Fibrosis; Proteome; Responder; Transcriptome