B 型钠尿肽抑制心衰患者 SERCA2a 的表达和功能

IF 1.2 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Yuting Zhai, Junhong Chen, Rongsheng Kan, Haochen Xuan, Chaofan Wang, Dongye Li, Tongda Xu
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引用次数: 0

摘要

B 型钠尿肽(BNP)具有保护心血管的特性;然而,人们对 BNP 的副作用还没有足够的重视。至于肌浆/内质网钙离子 ATP 酶 2a(SERCA2a),它曾一度被认为是治疗心力衰竭(HF)的新靶点。然而,SERCA2a 基因疗法治疗心力衰竭的临床试验最终未能成功。研究发现,BNP 水平升高和 SERCA2a 表达减少是两种重要的心力衰竭特征,两者始终呈负相关。我们假设 BNP 会抑制 SERCA2a 的表达,从而对 SERCA2a 的表达和功能产生负面影响。我们在横向主动脉收缩诱导的 HF 小鼠和新生大鼠心肌细胞(NRCM)中测试了 BNP 对内源性 SERCA2a 表达和功能的影响。此外,为了验证 BNP 对外源 SERCA2a 基因转导功效的影响,将 BNP 加入到感染了过表达 SERCA2a 的腺病毒的心肌和心肌细胞中。在体内,BNP 水平升高,BNP 干预组和 HF 组的 SERCA2a 表达均降低,BNP 降低了心肌中过表达的外源 SERCA2a 蛋白。我们的体外数据显示,BNP 通过激活 cGMP 依赖性蛋白激酶 G,剂量依赖性地抑制了 NRCM 中总 SERCA2a 和外源性 SERCA2a 的表达。BNP 和 SERCA2a 之间的反向关系应在通过 BNP 或 SERCA2a 基因疗法治疗 HF 时引起重视。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
B-Type Natriuretic Peptide Inhibits the Expression and Function of SERCA2a in Heart Failure.

B-type natriuretic peptide (BNP) possesses protective cardiovascular properties; however, there has not been sufficient serious consideration of the side effects of BNP. As for sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), it was once considered a new target for the treatment of heart failure (HF). Nevertheless, clinical trials of SERCA2a gene therapy in HF have finally become unsuccessful. Research has found that elevated BNP levels and decreased SERCA2a expression are two important HF characteristics, which are always negatively correlated. We hypothesize that BNP inhibits SERCA2a expression and, therefore, exerts negative effects on SERCA2a expression and function.The effects of BNP on endogenous SERCA2a expression and function were tested in mice with HF induced by transverse aortic constriction and neonatal rat cardiomyocytes (NRCM). Furthermore, to verify the effects of BNP on exogenous SERCA2a gene transduction efficacy, BNP was added to the myocardium and cardiomyocytes infected with an adenovirus overexpressing SERCA2a.In vivo, BNP levels were increased, SERCA2a expression was reduced in both the BNP intervention and HF groups, and BNP reduced the overexpressed exogenous SERCA2a protein in the myocardium. Our in vitro data showed that BNP dose-dependently inhibited the total and exogenous SERCA2a expression in NRCM by activating the cGMP-dependent protein kinase G. BNP also inhibited the effects of SERCA2a overexpression on Ca2+ transience in NRCM.The expression and function of endogenous and exogenous SERCA2a are inhibited by BNP. The opposite relationship between BNP and SERCA2a should be given serious attention in the treatment of HF via BNP or SERCA2a gene therapy.

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来源期刊
International heart journal
International heart journal 医学-心血管系统
CiteScore
2.50
自引率
6.70%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.
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