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环肽RD808可减轻β-肾上腺素能受体自身抗体诱导的心肌损伤。

Cyclic peptide RD808 reduces myocardial injury induced by β-adrenoreceptor autoantibodies.

作者信息

Dong Yu, Bai Yan, Zhang Shangyue, Xu Wenli, Xu Jiahui, Zhou Yi, Zhang Suli, Wu Ye, Yu Haicun, Cao Ning, Liu Huirong, Wang Wen

机构信息

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.

Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases, Capital Medical University, Beijing, China.

出版信息

Heart Vessels. 2019 Jun;34(6):1040-1051. doi: 10.1007/s00380-018-1321-3. Epub 2018 Dec 15.

Abstract

Autoantibodies against the second extracellular loop of β-adrenergic receptor (β-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 β-AA. Researchers are investigating the roles of cyclic peptides that mimic the structure of relevant epitopes on the β-AR-EC in a number of immune-mediated diseases. Here, we used a cyclic peptide, namely, RD808, to neutralize β-AA, consequently alleviating β-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 β-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 β-AA.

摘要

针对β-肾上腺素能受体(β-AA)第二个细胞外环的自身抗体已被证明与心血管疾病的发生有关。最近,人们对去除这些自身抗体的策略,特别是中和β-AA的治疗性肽,产生了浓厚兴趣。研究人员正在研究模拟β-AR-EC上相关表位结构的环肽在多种免疫介导疾病中的作用。在此,我们使用一种环肽,即RD808,来中和β-AA,从而减轻β-AA诱导的心肌损伤。我们在体外和体内研究了RD808对心肌的保护作用。发现RD808可提高心肌细胞的存活率;此外,在β-AA转移模型中,它可减少心肌坏死和凋亡,并改善BalB/c小鼠的心脏功能。体外和体内实验表明,RD808存在时心肌自噬增加,这可能有助于其心脏保护作用。我们的研究结果表明,RD808可减轻β-AA诱导的心肌损伤。

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