| Objective To determine whether autoantibodies against the G-protein- coupled β2- adrenoceptors are related to chronic heart failure (CHF) caused by different heart diseases. In addition, a rat myocardial infarction model was set up and occurrence frequency as well as the titers of autoantibodies against the cardiac β2-adrenoceptors were measured during development of ischemic heart failure so as to clarify the relationship between cardiac function and autoantibodies. Furthermore, the effects of generated autoantibodies on the heart rate in cultured myocyte were observed.Methods (1) Synthetic peptides, which corresponded to amino acids sequences of the second extracellular loop of human β2-adrenoceptor, were used as antigens in an Streptavidin- Enzyme-Linked Immunosorbent Assay (SA-ELISA) to screen sera from 267 subjects. Among them 206 had CHF caused by different heart diseases. The remaining 61 healthy donors were as control. (2) Rat myocardial infarction (MI) model was contructed by ligating the coronary artery. The occurrence frequency and titre of antibodies were determined by SA-ELISA during development of ischemic heart failure. (3) The positive sera for anti-β2-adrenoceptor autoantibodies were added to the medium of cultured neonatal rat cardiomyocyte to observe the effects of antibody on the heart beating rate.Results (1) The frequency of autoantibodies against β2-adrenoceptor in CHF group was significantly higher than that in NC. The geometric mean titers of autoantibodies against β2-adrenoceptor in patients with CHF were 1:89, which was also substantially higher than those of 1:35 (P<0.01) in NC；There were no significant differences between three groups of heart failure. (2) In rat MI model, the frequency of autoantibodies against β2-adrenoceptor was 46.8% at 4 weeks after coronary ligation, being substantially higher than the control of 16.0% in SH group(P<0.05); At 12 weeks, it was 56.3%, being substantially higher than the control of 15.4% in SH group(P<0.05); In the mean time, they were all higher than those before operation; There were significant differences on the frequencies in different periods of MI model(P<0.002)；With, however, no significant differences in the autoantibody titers between MI and SH groups as well as within each group. (3) From the experiment data, we found that the peak value of autoantibody against β2-adrenoceptor emerged at 4 weeks after treatment, while the changes in heart function took place at 1～2 weeks after treatment. Thus, we can see that the generation of autoantibody occured later than the cardiac functional changes. (4) Terbutaline Sulfate, an agonist of β2- adrenoceptor, could decrease the heart rates from 20.2±6.20 per 15 seconds before treatment to 16.92±4.89 , 13.17±3.21 , 11.85±2.84 at 5, 15 and 30 minutes after treatment respectively; The autoantibodies against β2- adrenoceptor could decrease the heart rates from 26.43±3.63 per 15 seconds before treatment to 9.42±3.03, 10.00±1.76, 9.25±2.56 at 5, 15 and 30 minutes after treatment respectively. Moreover , its action didn't attenuate with time. The antoantibodies displayed analogous agonistic activity. Conclusions (1) Our study indicated that autoantibodies against the G-protein-coupled β2-adrenoceptors not only exist in the sera of patients with heart failure resulting from different heart diseases, but also their titers were significantly higher than those in normal control group. There were no significant differences in frequencies of autoantibodies against β2-adrenoceptors between three different groups of heart failure. (2) In rat myocardial infarction model, the frequencies of autoantibody against β2- adrenoceptors at 4 weeks and 12 weeks after treatment were higher than those in SH group and also higher than those before treatment. There were no significant differences in the autoantibody titers between MI and SH groups and within each group; (3) It was shown that the autoantibodies against β2-adrenoceptors occurred temporally after the appearance of cardiac functional... |
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