Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

• Published in: Biochemical and biophysical research communications 2015-09, Vol.465 (1), p.119-124
• Main Authors: Saygili, Erol, Noor-Ebad, Fawad, Schröder, Jörg W., Mischke, Karl, Saygili, Esra, Rackauskas, Gediminas, Marx, Nikolaus, Kelm, Malte, Rana, Obaida R.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANGIOGENESIS; Animals; Animals, Newborn; Autoantibodies; Autoantibodies - blood; Autoantibodies - pharmacology; Cardiomyocytes; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Dilated - immunology; Cardiomyopathy, Dilated - pathology; Cardiomyopathy, Dilated - therapy; CELL CULTURES; CELL PROLIFERATION; Cell Proliferation - drug effects; CONCENTRATION RATIO; CONTROL; Dilated cardiomyopathy; FIBROBLASTS; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression; GROWTH FACTORS; HEART; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - pathology; Humans; HYPERTROPHY; Immunoglobulin G - blood; Immunoglobulin G - pharmacology; IMMUNOGLOBULINS; Immunosorbent Techniques; ISCHEMIA; MESSENGER-RNA; Myocardial Contraction; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; PATIENTS; PEPTIDES; Primary Cell Culture; RATS; Rats, Sprague-Dawley; SIGNALS; THERAPY; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; VEGF
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.07.143

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. 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. 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