Aim: 

Endothelin-1 (ET) is involved in many processes of heart function. Its effects are mediated via specific G-protein-coupled receptor subtypes ETA and ETB. Autoantibodies (AAB) against ETA-R were found in sera of patients with cardiovascular diseases. They exert a negative chronotropic effect in cultured rat cardiomyocytes antagonized by the ETA-R antagonist BQ 610. We examined cellular localization of ETA-R in cultured human smooth muscle cells and cell cultures of 3-day-old heart myocytes isolated from neonatal Wistar rats.

Methods: 

Cell cultures were incubated with AAB against ETA-R (1:100) for 1h. AAB were affinity purified from sera of patients. Incubation of cells with commercial ETA-R-AB, ET-1 peptide and free of primary AB served as controls. Thereafter, cells were fixed and stained with corresponding secondary AB for immunofluorescence.

Results: 

Presence of ETA-R was demonstrated on surface of cells of smooth muscle and heart. The intensity of immunofluorescence was different in variable cell types. In lesser extent ETA-R were also detected in the cell nuclei. In controls, no specific reaction was seen.

Conclusion: 

Results indicate that AAB against ETA-R found in sera of patients with heart diseases might bind to membrane ETA-R and contribute to progression of heart dysfunction.

Supported by DFG/DAAD and VEGA