system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adrenergic beta-Agonists, Animals, Autoantibodies, Cardiomyopathy, Dilated, Cell Line, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases, Humans, Isoproterenol, MAP Kinase Signaling System, Mice, Myocardium, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Stimulation, Chemical, Transfection.
user
Are anti-beta1-adrenergic receptor autoantibodies potent stimulators of the ERK1/2 pathway in cardiac cells? Context: Antibodies specific for the beta1-adrenergic receptor (beta1AR) are highly prevalent in patients with idiopathic dilated cardiomyopathy (DCM) and known to contribute to the pathogenesis of heart failure, though the precise molecular mechanisms involved are largely unknown. We have explored the effects of beta(1)AR autoantibodies obtained from DCM patients on extracellular signal-regulated kinase (ERK) activation in murine cardiomyocytes. We find that human beta(1)AR autoantibodies potently stimulate ERK1/2 in cardiac cells by using signalling pathways different from those triggered by the classic beta-agonist isoproterenol, also leading to a different pattern of activated ERK subcellular localization. The extent of ERK stimulation by endogenous cardiac beta(1)AR is markedly enhanced in the presence of both beta(1)AR-autoantibodies and isoproterenol. Interestingly, beta(1)AR-autoantibody-mediated ERK activation is not blocked by some betaAR antagonists used in the treatment of heart failure.
assistant
Our results suggest that these antibodies elicit a distinct beta(1)AR active conformation that would lead to the engagement of signaling effectors different from those recruited by classic beta-agonists, a finding that could lead to better understanding of DCM pathogenesis and aid in designing diagnostic and therapeutic strategies. Final Decision: yes