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15.12.2018 | Original Article | Ausgabe 6/2019

Heart and Vessels 6/2019

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

Zeitschrift:
Heart and Vessels > Ausgabe 6/2019
Autoren:
Yu Dong, Yan Bai, Shangyue Zhang, Wenli Xu, Jiahui Xu, Yi Zhou, Suli Zhang, Ye Wu, Haicun Yu, Ning Cao, Huirong Liu, Wen Wang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00380-018-1321-3) contains supplementary material, which is available to authorized users.

Abstract

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.

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Zusatzmaterial
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_MOESM1_ESM.tif
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_MOESM2_ESM.tif
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_MOESM3_ESM.tif
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_MOESM4_ESM.tif
Supplementary material 5 (DOC 44 kb)
380_2018_1321_MOESM5_ESM.doc
Literatur
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