Abstract 2961: Effects of Long-Term Immunization with Synthetic Peptides Corresponding to the Sequence of the Second Extracellular Loop of either Beta1-Adrenoceptor or M2-Muscarinic Receptor on Cardiac Activity in Rats
Objective: To determine whether the autoantibodies against β1-adrenergic and M2-muscarinic receptor are related to patients with elder dilated cardiomyopathy.
Methods: The model of cardiomyopathy was created by immunizing rats for 18 months with synthetic peptides of the second extracellular loop of either β1-adrenoceptor or M2-muscarinic receptor. Ninety rats were divided equivalently into three groups: control, β1 group (immunized with the peptide of the β1-adrenoceptor) and M2 group (immunized with the peptide of the M2-muscarinic receptor). The percentage of total T cell, helper/induce T cells and suppressor/cytotoxic T cells were measured.
Results: High-titers of anti-peptide antibodies were found in the sera from groups of immunized rats throughout the study period, but only a low titer of antibodies were found in the sera from some control rats and immunized rats. The ratio of helper/suppressor T-cells were significantly higher in immunized groups than that in the control group after 7 days to 3 month of immunization. The myocardial receptor density of immunized groups displayed a strong trend toward receptor up-regulation after 12 months of immunization, but down-regulation during 18 month. The immunized rats displayed significantly enlarged ventricles and thinner walls compared with the control. However, compared with enlarged cavities in both left and right ventricles in β1 group, the right ventricles were mainly affected in the M2 group. Moreover, the hearts of rats from immunized groups demonstrated significant morphological alterations, including focal myofibrillar lysis, loss of normal myofilament banding pattern with hyper contraction bands, mitochondrial swelling and condensation, sarcoplasmic vacuolation and deposition of dense granules in both the sarcoplasm and myofibrils. Eighteen months after immunization, the left ventricular systolic and diastolic functions in immunized groups were remarkably lowered than that of the control group.
Conclusion: Immunization by peptide, corresponding to the target sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy, induces morphological and functional changed in the heart similar to those found in the human heart diseases.