title: Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes.
abstract: BACKGROUND
  Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated.
  
  
  METHODS
  Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes.
  
  
  RESULTS
  Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post-IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05).
  
  
  CONCLUSIONS
  The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated.
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. Electronic address: erol.saygili@med.uni-duesseldorf.de.
authors.forename: Erol
authors.initials: E
authors.lastname: Saygili
authors.affiliation: Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany.
authors.forename: Fawad
authors.initials: F
authors.lastname: Noor-Ebad
authors.affiliation: Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany.
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Schröder
authors.affiliation: Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mischke
authors.affiliation: Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
authors.forename: Esra
authors.initials: E
authors.lastname: Saygili
authors.affiliation: Department of Cardiovascular Medicine, Vilnius University Hospital Santariskiu Klinikos, Vilnius University, Lithuania.
authors.forename: Gediminas
authors.initials: G
authors.lastname: Rackauskas
authors.affiliation: Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
authors.forename: Obaida R
authors.initials: OR
authors.lastname: Rana
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology*; D007163:Immunosorbent Techniques; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Autoantibodies; Cardiomyocytes; Dilated cardiomyopathy; Hypertrophy; VEGF