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(Circulation. 1998;98:2470-2476.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Agonistic Anti-ß₁-Adrenergic Receptor Autoantibodies From Cardiomyopathy Patients Reduce the ß₁-Adrenergic Receptor Expression in Neonatal Rat Cardiomyocytes

Svenia Podlowski, PhD; Hans Peter Luther, MD; Rosemarie Morwinski, PhD; Johannes Müller, MD; ; Gerd Wallukat, PhD

From the Max Delbrück Center for Molecular Medicine Berlin-Buch (S.P., H.P.L., R.M., G.W.) and the German Heart Institute Berlin (S.P., J.M.), Germany.

Correspondence to Gerd Wallukat, Max Delbrück Center, Department of Molecular Cardiology, Robert Rössle Straße 10, 13125 Berlin, Germany. E-mail molcard{at}orion.rz.mdc-berlin.de

Background—Autoantibodies directed against the ß₁-adrenergic receptor have been described in patients with dilated cardiomyopathy. These autoantibodies exert an agonistic, chronotropic effect on spontaneously beating cultured neonatal rat cardiomyocytes. We studied the effect of such antibodies on ß₁-adrenergic receptor expression.

Methods and Results—Cardiomyocytes were incubated with either the ß-adrenergic agonist isoproterenol or autoantibodies for 72 hours. ß-Adrenergic receptor expression was studied on the mRNA level with semiquantitative reverse transcription–polymerase chain reaction and on the protein level with immunoblotting. Isoproterenol downregulated both mRNA and ß₁- and ß₂-adrenergic receptor protein subtypes, whereas the anti–ß₁-adrenergic receptor autoantibodies decreased only the ß₁-adrenergic receptor mRNA and protein. Long-term incubation of cultured cardiomyocytes with isoproterenol or the anti–ß₁-adrenergic receptor autoantibodies reduced the acute stimulatory effect of isoproterenol on the myocytes. These effects were prevented by incubating the cells with isoproterenol in the presence of propranolol or with anti–ß₁-adrenergic receptor autoantibodies in the presence of bisoprolol. Bisoprolol also abolished the reduction of the ß₁-adrenergic receptor expression caused by longer-term incubation with isoproterenol and the autoantibodies.

Conclusions—We conclude that after longer-term treatment with the anti–ß₁-adrenergic receptor autoantibodies, the rat cardiomyocytes showed a ß-adrenergic receptor expression similar to that observed in failing hearts from patients with dilated cardiomyopathy.

Key Words: receptors, adrenergic, beta • antibodies • cardiomyopathy • myocytes • heart failure

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