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).

CONCLUSION:

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: Erol Saygili, Fawad Noor-Ebad, Jörg W Schröder, Karl Mischke, Esra Saygili, Gediminas Rackauskas, Nikolaus Marx, Malte Kelm, Obaida R Rana
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 465 Issue 1 Pg. 119-24 (Sep 11 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26248134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Autoantibodies
• Immunoglobulin G
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat

Topics

• Animals
• Animals, Newborn
• Autoantibodies (blood, pharmacology)
• Cardiomyopathy, Dilated (genetics, immunology, pathology, therapy)
• Cell Proliferation (drug effects)
• Fibroblasts (drug effects, metabolism, pathology)
• Gene Expression
• Heart Ventricles (drug effects, metabolism, pathology)
• Humans
• Immunoglobulin G (blood, pharmacology)
• Immunosorbent Techniques
• Myocardial Contraction
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Primary Cell Culture
• Rats
• Rats, Sprague-Dawley
• Vascular Endothelial Growth Factor A (genetics, metabolism)