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Takotsubo心肌病动物模型中的心脏和血管基因谱

Cardiac and vascular gene profiles in an animal model of takotsubo cardiomyopathy.

作者信息

Ueyama Takashi, Yamamoto Yuta, Ueda Kazuki, Kawabe Tetsuya, Hano Takuzo, Ito Takao, Tsuruo Yoshihiro, Ichinose Masao, Yoshida Ken-ichi

机构信息

Department of Anatomy and Cell Biology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, 641-8509, Japan.

出版信息

Heart Vessels. 2011 May;26(3):321-37. doi: 10.1007/s00380-010-0070-8. Epub 2010 Dec 3.

Abstract

We investigated cardiac and vascular gene profiles in response to immobilization stress (IMO) in rats, an animal model of emotional stress-induced takotsubo cardiomyopathy using microarray analysis, followed by re-confirmation with real-time reverse transcription-polymerase chain reaction. Expression levels of the identified genes were further estimated by pretreatment with an α1-adrenoceptor blocker and/or a β1-adrenoceptor blocker. In response to IMO, expression of 46 genes was significantly altered in the heart and that of 49 genes was significantly altered in the aorta. Pathway analysis with DAVID Bioinformatics Resources indicated that regulation of transcription and response to endogenous stimulation were the top two scoring pathways. Altered expression of cardiac genes was blunted by pretreatment with a β1-adrenoceptor blocker or α1 + β1-adrenoceptor blockers. In contrast, that of aortic genes was blunted by pretreatment with an α1-adrenoceptor blocker or α1 + β1-adrenoceptor blockers. Activation of α1-adrenoceptor in the blood vessels or activation of β1-adrenoceptors in the heart were mainly responsible for emotional stress-induced alteration of cardiac and vascular gene profiles.

摘要

我们使用微阵列分析研究了大鼠在制动应激(IMO)(一种情绪应激诱导的应激性心肌病动物模型)下心脏和血管的基因谱,随后通过实时逆转录聚合酶链反应进行重新确认。通过用α1肾上腺素能受体阻滞剂和/或β1肾上腺素能受体阻滞剂预处理,进一步评估已鉴定基因的表达水平。响应IMO时,心脏中有46个基因的表达显著改变,主动脉中有49个基因的表达显著改变。使用DAVID生物信息学资源进行的通路分析表明,转录调控和对内源性刺激的反应是得分最高的前两条通路。用β1肾上腺素能受体阻滞剂或α1 + β1肾上腺素能受体阻滞剂预处理可减弱心脏基因表达的改变。相反,用α1肾上腺素能受体阻滞剂或α1 + β1肾上腺素能受体阻滞剂预处理可减弱主动脉基因表达的改变。血管中α1肾上腺素能受体的激活或心脏中β1肾上腺素能受体的激活是情绪应激诱导的心脏和血管基因谱改变的主要原因。

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