The role of Candiotrophin-1 and its receptoi component, rpbi, in the heart.

Candiotropin-1 及其受体成分 rpbi 在心脏中的作用。

• 批准号: 10670647
• 负责人: AOYAMA Takesh
• 金额: $ 2.05万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670647/
• 关键词: myocardial infarction; rentricular remodeling; cardiotrophin-1; gp-130; cardiotrophin-1; サイトカイン(cytokine); 心筋梗塞(myocardial infarction); 左室リモデリング(ventriculer remodeling)

Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting in myocardial cell hypertrophy. We examined the role of CT-1 and gp130 system in the two rat models of congestive heart failure. TO clarify the role of CT-1 and the gp130-signaling pathway during ventricular remodeling after myocardial infarction. we examined the expression of CT-1 and gp130 in a rat model of myocardial infarction. All animals developed large myocardial infarctions and progressive left ventricular dilatation and inadequate hypertrophy of the surviving myocardium were confirmed by echocardiography. CT-1 and gp130 mRNA levels were determined by semiquantitative RT-PCR followed by Southern blotting. The densitometric analysis of the Southern blots revealed a significant increase in CT-1 and gp130 mRNA levels compared with those of the sham-operated rats at 1, 3, 7, 14, 28 and 56 days post-infarct in the infarct area, t … More he ventricular septum and right ventricle. The protein levels of CT- and gp130, determined by Western blot analysis, were significantly increased compared to those of sham-operated rats, and peaked in the acute stage and declined thereafter in the three regions described above. Immunohistochemical staining showed that CT-1 and gp130-immunoreactivities were detected in cardiomyocytes and fibroblast-like cells and that the intensity of staining was increased at 7days post-infarct compared with that in sham-operated rats. An augmented CT-1 and gp130 system thus seems to play an important role during ventricular remodeling after myocardial infarction. We also determined the expression levels of CT-1 and gp130 during the transition from cardiac hypertrophy to heart failure using Dah1-salt-sensitive rats with hypertension. CT-1 expression was increased in the stage of heart failure, in which we confirmed the assembly of sarcomeric units in series. Thus, CT-1 contributes to the ventricular dilatation by elongating cardiomyocytes. These findings in the two heart failure models strongly suggest that CT-1 plays a central role in the ventricular dilatation in heart failure. Less

促肌生长素-1（CT-1）是一种有效的细胞因子，其通过gp 130信号传导刺激心肌细胞中肌节单位的串联组装，导致心肌细胞肥大。本研究探讨了CT-1和gp 130系统在两种心力衰竭大鼠模型中的作用。目的：探讨CT-1和gp 130信号通路在心肌梗死后心室重构中的作用。我们检测了CT-1和gp 130在大鼠心肌梗死模型中的表达。超声心动图证实所有动物均发生大面积心肌梗死和进行性左心室扩张，存活心肌肥厚不充分。CT-1和gp 130的mRNA水平通过半定量RT-PCR和Southern印迹法测定。Southern印迹分析显示，与假手术组相比，梗死后1、3、7、14、28和56天，梗死区CT-1和gp 130 mRNA水平显著升高，与假手术组相比，梗死后1、3、7、14、28和56天，CT-1和gp 130 mRNA水平显著升高。 ...更多信息 室间隔和右心室。蛋白质水平的CT-和gp 130，确定通过Western印迹分析，显着增加相比，那些假手术大鼠，并在急性期达到峰值，此后在上述三个区域下降。免疫组织化学染色显示，CT-1和gp 130在心肌细胞和成纤维细胞样细胞中呈阳性表达，与假手术组相比，梗死后7 d染色强度增强。因此，增强CT-1和gp 130系统似乎在心肌梗死后心室重塑过程中发挥重要作用。我们还确定了CT-1和gp 130的表达水平，从心脏肥大的心脏衰竭的过渡使用Dah 1盐敏感的高血压大鼠。CT-1表达在心力衰竭阶段增加，我们证实了肌节单位的组装。因此，CT-1通过延长心肌细胞而有助于心室扩张。在两种心力衰竭模型中的这些发现强烈地表明CT-1在心力衰竭的心室扩张中起核心作用。少

项目成果

Takeshi Aoyama et al. 他7名: "Augmented expression of cardiotrophin-1 and its receptor component, gp130, in both left and right ventricles after myocardial infarction in the rat"Journal of Molecular Cellular Cardiology. (in press). (2000)

Takeshi Aoyama 等人和 7 人：“大鼠心肌梗死后左心室和右心室中心肌营养蛋白-1 及其受体成分 gp130 的表达增强”《分子细胞心脏病学杂志》（2000 年出版）。

Eiji Shinoda, Yoshiki Yui, Ryuichi Hattori, Misaki Tanaka, Inoue Reiko, Takeshi Aoyama, Yoshihito Takimoto, Youji Mitsui, Kaoru Miyahara, Yutaka Shizuta, Shigetaka Sasayama.: "Tissue factor inhibitor-2 is a novel mitogen for vascular smooth muscle cells"J

Eiji Shinoda、Yoshiki Yui、Ryuichi Hattori、Misaki Tanaka、Inoue Reiko、Takeshi Aoyama、Yoshihito Takimoto、Youji Mitsui、Kaoru Miyahara、Yutaka Shizuta、Shigetaka Sasayama。：“组织因子抑制剂-2 是一种新型血管平滑肌细胞有丝分裂原”

Yoshitaka Iwanaga, Yasuki Kihara, Asuka Yasaka, Takeshi Yoneda, Wataru Hayashida, Takeshi Aoyama, Shigetake Sasayama.: "Regulation of osteopontin in in vivo left ventricular hypertrophy and failure : a possible role of endogenous endothelin-1."Circ. Res..

Yoshitaka Iwanaga、Yasuki Kihara、Asuka Yasaka、Takeshi Yoneda、Wataru Hayashida、Takeshi Aoyama、Shigetake Sasayama.：“骨桥蛋白在体内左心室肥大和衰竭中的调节：内源性内皮素-1 的可能作用。”Circ。

Yoshitaka Iwanaga, Yasuki Kihara, Takeshi Yoneda, Takeshi Aoyama, Shigetake Sasayama.: "Modulation of in vivo cardiac hypertrophy with IGF-1 and ACE inhibitor"J. Am. Coll. Cardiol.. (in press). (2000)

Yoshitaka Iwanaga、Yasuki Kihara、Takeshi Yoneda、Takeshi Aoyama、Shigetake Sasayama.：“用 IGF-1 和 ACE 抑制剂调节体内心脏肥大”J。

Takeshi Aoyama et al.: "Augmented expression of cardiotrophin-1 and its receptor component,gp130,in both loft and right ventricles after myocardial inforstion in the rat." Circulation. (in press).

Takeshi Aoyama 等人：“大鼠心肌梗死后，心肌营养蛋白-1 及其受体成分 gp130 在心室和右心室中的表达增强。”