Relationship of myocardial remodeling to the genesis of serum autoantibodies to cardiac beta(1)-adrenoceptors and muscarinic type 2 acetylcholine receptors in rats.

• OBJECTIVES: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Animals

Autoantibodies

blood

Autoimmunity

Body Weight

CD4-CD8 Ratio

Cardiomyopathy

Dilated

immunology

pathology

Disease Models

Animal

Female

Heart

anatomy & histology

Male

Myocardium

cytology

immunology

Organ Size

Rats

Rats

Wistar

Receptors

Adrenergic

beta-1

immunology

metabolism

Receptors

Muscarinic

immunology

metabolism

Ventricular Remodeling

immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)