Impaired IGF-I signaling of hypertrophic hearts in the development phase of hypertension in genetically hypertensive rats

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题名:	Impaired IGF-I signaling of hypertrophic hearts in the development phase of hypertension in genetically hypertensive rats
作者:	郭薇雯(Wei-Wen Kuo);(Chia-Yih Chu);吳介信(Chieh-Hsi Wu);林子恩(Lin, Tzu-En);(Jer-Yuh Liu);(Yi-Hsien Hsieh);(Kwo-Chang Ueng);李信達(Shin-Da Lee);(Dennis Jine-Yuan Hsi);黃志揚(Chih-Yang Huang)*
贡献者:	醫學院生物科技學系
关键词:	insulin-like growth factor-1 signalling pathway;cardiac hypertrophy;hypertension;SHR and SPSHR
日期:	2005-09
上传时间:	2009-08-21 11:03:39 (UTC+8)
摘要:	Insulin-like growth factor-I (IGF-I) signalling is reported to contribute to the modulation of blood pressure and set survival and hypertrophic responses in cardiac tissue. However, whether IGF-I signalling normally acts in cardiac tissues of hypertensive rats is unknown. In this study, using spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SPSHR), both with early blood pressure increases, and Wistar-Kyoto (WKY) rats as controls, we measured the hypertrophic and IGF-I signalling activity changes in rat hearts at 4, 6 and 12 weeks of age. Both SHR and SPSHR were found to have significantly increased blood pressures and ratios of heart- and left ventricle- to body weight at 12 weeks of age. However, IGF-IR and its downstream signalling, including the protein levels of PI3K and phosphorylated Akt, known to maintain physiological cardiac hypertrophy and cardiomyocyte survival, were downregulated. The results of dot blotting showed that cardiac mRNA levels of IGF-I in hypertensive rats were higher than those in controls starting from the age of 4 weeks. This difference suggests the increased ligand IGF-I mRNA levels may be a compensatory response caused by the impaired IGF-I signalling. Moreover, enhanced cardiac cytosolic cytochrome-c, a mitochondria-dependent apoptotic pathway component, tended to occur in both hypertensive rats, although it did not reach a significant level. These findings indicate that impaired IGF-IR signalling occurs at early stages, and it may contribute, at least partially, to the development of hypertension and pathological cardiac hypertrophy and to cardiomyocyte apoptosis at later stages in SHR and SPSHR.
關聯:	CELL BIOCHEMISTRY AND FUNCTION23(5):325~331
显示于类别:	[生物科技學系暨碩士班] 期刊論文

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