JACC:Takotsubo综合征发病机制的研究

2017-08-16 nanchao.H MedSci原创

Takotsubo综合征(TTS)是一种急性左室功能不全,并且急性期可能会致命的临床综合征。目前,TTS的发病机制尚未阐明。近日,在国际心血管权威杂志JACC上发表了一篇旨在建立TTS体外引导性多能干细胞(IPSC)模型以研究儿茶酚胺-β信号通路是否在IPSC-心肌细胞(CMs)有所改变,并探究其机制的研究。本研究将TTS患者和正常对照的体细胞提取,诱导为IPSC,并分化为心肌细胞。三个月大的心肌

Takotsubo综合征(TTS)是一种急性左室功能不全,并且急性期可能会致命的临床综合征。目前,TTS的发病机制尚未阐明。近日,在国际心血管权威杂志JACC上发表了一篇旨在建立TTS体外引导性多能干细胞(IPSC)模型以研究儿茶酚胺-β信号通路是否在IPSC-心肌细胞(CMs)有所改变,并探究其机制的研究。

本研究将TTS患者和正常对照的体细胞提取,诱导为IPSC,并分化为心肌细胞。三个月大的心肌细胞在儿茶酚胺的刺激下激活了神经体液刺激,并进一步探索β-肾上腺素信号通路在TTS心肌细胞中的作用。

研究结果显示,β-肾上腺素信号通路的上调激活了心脏应激标志物NR4A1;环磷酸腺苷和环磷酸腺苷水平; ryr2-s2808,pln-s16,tni-s23 / 24,和cav1.2-s1928的过度磷酸化,并减少钙瞬变衰减时间50%。这些细胞信号的变化主要是由TTS中的β1-肾上腺受体信号介导的。TTS-iPSC-CMs来源的心肌收缩力有损害,并且对异丙肾上腺素更加敏感。此外,在儿茶酚胺刺激下的TTS-iPSC-CMs的电活动也有所改变,并且存在脂质的累积。

本研究表明,Takotsubo综合征患者的β-肾上腺素信号水平是升高的,并且对儿茶酚胺的敏感性有所增加。

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    2018-05-04 hbwxf
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    2017-08-18 axin015
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    2017-08-16 zwjnj2

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