OBJECTIVETo investigate the biological effects of anti-beta(3) adrenoceptor (beta(3)-AR) autoantibody in the serum of patients with heart failure, which may contribute to a new therapeutic clue for heart failure.

METHODSThe synthetic peptide of the second extracellular loop of the beta(3)-AR was used as the antigen to screen sera of patients with heart failure and of healthy controls by using enzyme-linked immunosorbent assay. IgG in the patients group of positive autoantibody sera was prepared by using a MabTrap Kit (Amersham) following the manufacturer's instructions. The effects of IgG per each group both on contractile response of adult isolated cardiomyocytes and on beating frequency of cultured neonatal rat cardiomyocytes were observed.

RESULTSThe positive rate of anti-beta(3)-AR autoantibody was 26.7% (mean antibody titer: 1:43.27 +/- 2.71) or 11.0% (mean antibody titer: 1:14.59 +/- 1.61) in patients or healthy subjects, respectively P < 0.05. Compared with the control group, the autoantibody against beta(3)-AR from the patients group decreased cell shortening amplitude/cell shortening 3.84% +/- 0.33%, the velocity of shortening -0.47 microm/s +/- 0.07 microm/s and relengthening 0.17 microm/s +/- 0.02 microm/s in adult isolated cardiac myocytes, respectively. The autoantibody in the patients group decreased the beating rate in cultured neonatal rat cardiac myocytes by 47.1 beats/min +/- 8.11 beats/min, which could have a 6-hour continuance. This decreasing was not modified by Nadolol (beta(1)-AR and beta(2)-AR antagonist) in pretreating myocytes, but was nearly prevented by Bupranolol (nonselective beta-AR antagonist) or beta(3)-AR specific antigen.

CONCLUSIONIt seems reasonable to state that a high titer of the autoantibody against beta(3)-AR in the serum in patients with heart failure, which could have a negative inotropic and chronotropic effect, may be a part of pathophysiological mechanisms of heart failure.