Why the study?
How do autoantibodies against cardiac myosin lead to heart dysfunction in autoimmune myocarditis?
How do autoantibodies against cardiac myosin lead to heart dysfunction in autoimmune myocarditis?
Autoantibodies against cardiac myosin mimic beta-adrenergic receptors to induce pathogenic cell signaling and cardiomyopathy in experimental models.
Implicates anti-CM autoantibodies in beta-AR-driven experimental cardiomyopathy; hypothesis-generating for human autoimmune myocarditis.
The mechanisms by which autoantibodies against cardiac myosin (CM) may lead to heart dysfunction is unknown. We show that autoantibodies to CM in anti-CM sera and mAbs derived from experimental autoimmune myocarditis targeted the heart cell surface and induced Ab-mediated cAMP-dependent protein kinase A activity. Ab-mediated cell signaling of protein kinase A was blocked by CM, anti-IgG, or by specific inhibitors of the β-adrenergic receptor (β-AR) pathway. mAbs confirmed mimicry between CM and the β-AR. Passive transfer of purified Ab (IgG) from CM-immunized rats resulted in IgG deposition and apoptosis in the heart, leading to a cardiomyopathic heart disease phenotype in recipients. Our novel findings link anti-CM Ab with the β-AR and subsequent Ab-mediated cell signaling in the heart.
No takes yet. Share an insight, caveat, or question.
Li et al. (2006) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: