Abstract: Objective To investigate whether the reduced autophagy induced by β1- adrenergic receptor autoantibodies (β1-AA) could activate the endoplasmic reticulum stress (ERS) -induced apoptosis pathways in cardiomyocytes. Methods Rats were selected for immunization with a synthetic peptide corresponding to the second extracellular loop of the β1-AR (β1-AR-ECII). β1-AA in the serum were purified by affinity chromatograph. Antibody purity were determinated by SDS-PAGE. The autophagy related proteins such as Beclin1, LC3 and p62 were evaluated by Western blot. Expression of GRP78, CHOP and caspase-12 were evaluated by Western blot and immunohistochemistry which involved in ERS-induced cell apoptosis. Results Compared with the control group, the expression of Beclin1 and LC3 was decreased and the expression of p62 was increased after treatment for 12 h and 24 h with β1-AA. The expression of GRP78，CHOP and caspase-12 was increased after 12 h and 24 h with the existence of β1-AA. Inhibition of autophagy by 3MA further enhanced and pretreatment with Rapa partially attenuated ERS-mediated cardiomyocytes apoptosis induced by β1-AA. Conclusion 1) β1-AA could decrease autophagy and activate ERS-mediated apoptosis pathway in cardiomyocytes. 2) Decreased autophagy is involved in the activation of ERS-mediated cardiomyocyte apoptosis in cardiomyocytes induced by β1-AA.

Key words: Key words:β1-adrenergic receptor autoantibodies, autophagy, endoplasmic reticulum stress-induced apoptosis pathway