Cyclic peptide RD808 reduces myocardial injury induced by β1-adrenoreceptor autoantibodies

  • Yu Dong
  • Yan Bai
  • Shangyue Zhang
  • Wenli Xu
  • Jiahui Xu
  • Yi Zhou
  • Suli Zhang
  • Ye Wu
  • Haicun Yu
  • Ning Cao
  • Huirong LiuEmail author
  • Wen WangEmail author
Original Article


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.


β1-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.

Author contributions

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.

Supplementary material

380_2018_1321_MOESM1_ESM.tif (102 kb)
Figure S1. RD808 was purified by HPLC and MS. The purity of this peptide was > 98%. (A) HPLC result of RD808. (B) MS result of RD808 (TIF 103 kb)
380_2018_1321_MOESM2_ESM.tif (490 kb)
Figure S2. The LVEF declined at 8 weeks during β1-AA treatment. LVEF was detected in 16 weeks of β1-AA treatment mice, here ISO was used as a positive control of a classical heart failure model. Results showed that there was a significant decrease of left ventricular pump function with the existence of β1-AA at 8 weeks. These experiments have been conducted independently of the RD808-study. ISO: Isoproterenol. Data were expressed as means ± SD. *P<0.05 vs. Vehicle group, n=6 (TIF 491 kb)
380_2018_1321_MOESM3_ESM.tif (431 kb)
Figure S3. Level of LDH in supernatant of NRCMs.. Data were expressed as means ± SD. **P<0.01 vs. Vehicle group, #P<0.05 ##P<0.01 vs. β1-AA group, n=6 (TIF 432 kb)
380_2018_1321_MOESM4_ESM.tif (1.5 mb)
Figure S4. Safety assessment of RD808 in vitro. The cell survival rate and LDH release in supernatant of NRCMs were detected after challenged with different concentration of RD808 for different time. There was no significant change after RD808 administration compared to vehicle group. (A) Cell survival rate assay with CCK-8. (B) LDH in supernatant. Data were expressed as means ± SD. n=4 (TIF 1576 kb)
380_2018_1321_MOESM5_ESM.doc (44 kb)
Supplementary material 5 (DOC 44 kb)


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Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Yu Dong
    • 1
    • 2
  • Yan Bai
    • 1
    • 2
  • Shangyue Zhang
    • 1
    • 2
  • Wenli Xu
    • 1
    • 2
  • Jiahui Xu
    • 1
    • 2
  • Yi Zhou
    • 1
    • 2
  • Suli Zhang
    • 1
    • 2
  • Ye Wu
    • 2
  • Haicun Yu
    • 1
    • 2
  • Ning Cao
    • 1
    • 2
  • Huirong Liu
    • 1
    • 2
    Email author
  • Wen Wang
    • 1
    • 2
    Email author
  1. 1.Department of Physiology and Pathophysiology, School of Basic Medical SciencesCapital Medical UniversityBeijingChina
  2. 2.Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular DiseasesCapital Medical UniversityBeijingChina

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