Immunization with beta(1)-adrenoreceptor peptide induces cardiomyopathy-like changes in rabbit hearts

To investigate the importance of autoimmunity against beta(1)-adrenoreceptor in the pathogenesis of dilated cardiomyopathy (DCM).

Fourteen rabbits were divided equally into two groups. Rabbits in the immunized group (n = 7) were immunized monthly for one year with synthetic peptide corresponding to the second extracellular loop of the beta(1)-adrenoreceptor and adjuvant. Control rabbits received the mixture with the same procedure as described except with a substitution of saline for the corresponding peptide. During the study period, all rabbits were bled to assay the titers of antipeptide antibody and left ventricular ejection fractions (LVEFs) were measured by emission computed tomography. At the end of experiment, invasive cardiac function was measured and morphologic examinations were done.

High titers of antipeptide antibody were found in the sera from immunized rabbits throughout the study period in contrast to those from control rabbits. LVEFs were significantly higher in immunized rabbits than those of the control group at the 4th and 6th month. At the end of the experiment, the maximal rates of rise and decline of ventricular pressure of the immunized group were significantly lower than those of the control group. Morphological changes were found in immunized rabbits such as the enlargement of ventricles, myofibrillar lysis and necrosis, mitochondria swelling and condensation. No obvious alterations were noted in hearts of control rabbits.

Autoimmunity against the beta(1)-adrenoreceptor may be involved in the pathogenesis of dilated cardiomyopathy and beta(1)-adrenoreceptor antibody may play a role in the process.