Impaired IGF-I signalling of hypertrophic hearts in the developmental phase of hypertension in genetically hypertensive rats

Wei Wen Kuo, Chia Yih Chu, Chieh Hsi Wu, James A. Lin, Jer Yuh Liu, Yi Hsien Hsieh, Kwo Chang Ueng, Shin Da Lee, Dennis Jine Yuan Hsieh, His Hsien Hsu, Li Mien Chen, Chih Yang Huang

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)325-331
Number of pages7
JournalCell Biochemistry and Function
Volume23
Issue number5
DOIs
Publication statusPublished - Sep 2005
Externally publishedYes

Keywords

  • Cardiac hypertrophy
  • Hypertension
  • Insulin-like growth factor-1 signalling pathway
  • SHR and SPSHR

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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