Abstract 5655: Autoantibodies Against Endothelin-1 Receptors Are Involved in the Pathogenesis of Pulmonary Arterial Hypertension

TL;DRAbstract

Background In patients with pulmonary arterial hypertension (PAH) production of endothelin-1 (ET-1) is increased and elevated ET-1 plasma levels correlate with PAH severity. After repeated detection of agonistic antibodies against the ET-1 A receptor (ETA) in PAH patients’ sera we assessed their prevalence and properties. Methods Using spontaneously beating rat neonatal cardiomyocytes as bioassay we analyzed sera of PAH patients for the presence of autoantibodies (AABs) against ETA receptors. AABs were purified by affinity chromatography. Results At the time of AAB testing, the pulmonary vascular resistance (PVR) in the 58 evaluated PAH patients varied between 500 and 1920 dyn • sec • cm −5 (median 1088 dyn • sec • cm −5 ) and 45 (77.6%) were in functional NYHA/WHO class ≥ III. Of these 58 patients 44 (78.7%) tested positive for AABs against ETA receptors. ET-1 and the AABs against ETA exerted agonistic negative chronotropic effects on the neonatal cardiomyocytes (decrease in pulsation

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