Cyclic peptide RD808 reduces myocardial injury induced by β1-adrenoreceptor autoantibodies
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Autoantibodies against the second extracellular loop of β1-adrenergic receptor (β1-AA) have been shown to be involved in the development of cardiovascular diseases. Recently, there has been considerable interest in strategies to remove these autoantibodies, particularly therapeutic peptides to neutralize β1-AA. Researchers are investigating the roles of cyclic peptides that mimic the structure of relevant epitopes on the β1-AR-ECII in a number of immune-mediated diseases. Here, we used a cyclic peptide, namely, RD808, to neutralize β1-AA, consequently alleviating β1-AA-induced myocardial injury. We investigated the protective effects of RD808 on the myocardium both in vitro and in vivo. RD808 was found to increase the survival rate of cardiomyocytes; furthermore, it decreased myocardial necrosis and apoptosis and improved the cardiac function of BalB/c mice in a β1-AA transfer model. In vitro and in vivo experiments showed that myocardial autophagy was increased in the presence of RD808, which might contribute to its cardioprotective effects. Our findings indicate that RD808 reduced myocardial injury induced by β1-AA.
Keywordsβ1-Adrenergic receptor Autoantibody against the second extracellular loop of β1-adrenergic receptor Myocardial injury Cyclic peptide RD808
We acknowledge the assistance of Mrs. Ying Yang and Mrs. Qing Xu for surface plasmon resonance (SPR) technology and Doppler ultrasound for cardiac function detection in the Core Facility Center, Capital Medical University. Fundings were provided by the Natural Science Foundation of Beijing (7151001) to Wen Wang and 973 Special Preliminary Study Plan (2014CB560704) to Huirong Liu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conceived and designed the experiments: HL, WW. Performed the experiments: YD, YB, SZ, WX, JX, YZ, HY, NC. Analyzed the data: YD, YW. Contributed reagents/materials/analysis tools: SZ. Contributed to the writing of the manuscript: YD.
Conflict of interest
The authors declare the absence of any competing interest.
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