Abstract
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1-AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1-AAB-immunized rat model. Rapamycin, an mTOR inhibitor, restored myocardial apoptosis in the presence of β1-AABs. Further, we found that the early increase of autophagy was an adaptive stress response that is possibly unrelated to β1-AR, and the activation of the β1-AR and PKA contributed to late decreased autophagy. Then, after upregulating or inhibiting autophagy with rapamycin, Atg5 overexpression adenovirus or 3-methyladenine in cultured primary neonatal rat cardiomyocytes, we found that autophagy decline promoted myocardial apoptosis effectively through the mitochondrial apoptotic pathway. In conclusion, the reduction of apoptosis through the proper regulation of autophagy may be important for treating patients with β1-AAB-positive heart dysfunction.
Highlights
Cardiac dysfunction is one of the most common causes of cardiovascular disease[1], its pathogenesis has not been fully elucidated
We found that autophagy was significantly increased at 1 min, and the autophagic flux was Decreased autophagy participated in apoptosis of cardiomyocytes induced by β1-adrenoceptor autoantibodies (β1-AABs)
3-MA pretreatment led to increased caspase-9 activity and a decline in the red/green fluorescence ratio, indicating a further decrease in the Discussion In the present study, we observed that β1-AABs significantly increased apoptosis in the myocardial tissue of actively immunized rats and in cultured primary neonatal rat cardiomyocytes
Summary
Cardiac dysfunction is one of the most common causes of cardiovascular disease[1], its pathogenesis has not been fully elucidated. There are indications that β1-adrenoceptor autoantibodies (β1-AABs) can be detected in the serum of 40–60% of patients with cardiac dysfunction[3]. Autophagy, which is an important mechanism of maintaining cellular homeostasis, has been shown to influence the apoptosis[5]. Our group has shown that decreased autophagy induced by β1-AABs contributed to cardiomyocyte death and cardiac dysfunction[7]. Wang et al Cell Death and Disease (2018)9:406 of apoptosis. Whether autophagy influences cardiomyocyte apoptosis induced by β1-AABs is still unknown. An actively β1-AAB-immunized rat model and cultured primary neonatal rat cardiomyocytes were used to observe the possible mechanism of β1-AABinduced apoptosis from the autophagy perspective. The purpose is to show whether the regulation of autophagy may play a therapeutic role in β1-AAB-positive patients with heart disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
