Relationship of myocardial remodeling to the genesis of serum autoantibodies to cardiac beta(1)-adrenoceptors and muscarinic type 2 acetylcholine receptors in rats.
OBJECTIVE
We sought to investigate the mechanism responsible for the occurrence of anticardiac receptor autoantibodies.


BACKGROUND
Increasing evidence suggests the involvement of autoimmune mechanisms in the pathogenesis of a number of cardiovascular diseases. Among them, the biologic, functional and pathogenic properties of anticardiac receptor antibodies have been extensively investigated. However, the mechanism responsible for the occurrence of anticardiac receptor autoantibodies remains poorly understood.


METHODS
Two rat models (aortic banding [AB] and adriamycin [ADR] groups) were constructed. Determination of cardiac function and morphology and T-lymphocyte subtypes, enzyme-linked immunosorbent assay and cardiomyocyte cultures were performed.


RESULTS
It was shown, in the AB and ADR groups, that the frequency and titer of autoantibodies to beta(1) and muscarinic type 2 receptors were increased when myocardial remodeling occurred, as evidenced by significant cardiac morphologic changes, deposition of collagen and obvious functional impairment. This suggests that cardiac remodeling itself, in two disparate models of heart failure and cardiomyopathy, was able to trigger the genesis of anticardiac receptor autoantibodies. These autoantibodies have biologic effects similar to those seen in human autoantibodies. They have also shown a characteristic self-growth, as well as a time-course decline, suggesting that a negative finding of anticardiac receptor autoantibodies in sera of patients with heart disease does not necessarily imply that there is no autoimmune reaction involved in the pathogenesis.


CONCLUSIONS
Our results demonstrated that myocardial damage was able to trigger the occurrence of an autoimmune reaction, resulting in the genesis of anticardiac receptor autoantibodies with properties similar to those seen in patients with idiopathic dilated cardiomyopathy.
Liu
Hui Rong
HR
Laboratory of Cardiovascular Physiology, Shanxi Medical University, Taiyuan, China.
Zhao
Rong Rui
RR
Jiao
Xiang Ying
XY
Wang
Ying Yuan
YY
Fu
Michael
M
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D001835:Body Weight; D016516:CD4-CD8 Ratio; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000033:anatomy & histology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000276:immunology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000276:immunology* / Q000378:metabolism; D020257:Ventricular Remodeling / Q000276:immunology*
D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic