Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart

Jin Ming Hwang, Yi Jiun Weng, James A. Lin, Da Tian Bau, Fu Yang Ko, Fuu Jen Tsai, Chang Hai Tsai, Chieh Hsi Wu, Pei Cheng Lin, Chih Yang Huang, Wei Wen Kuo

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33 Citations (Scopus)

Abstract

Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1α and Shh. The relationship between HIF-1α and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1α signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1α and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume311
Issue number1-2
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Keywords

  • H9c2 cells
  • HIF-1α
  • Hypoxia
  • Ischemia
  • Shh

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Hwang, J. M., Weng, Y. J., Lin, J. A., Bau, D. T., Ko, F. Y., Tsai, F. J., Tsai, C. H., Wu, C. H., Lin, P. C., Huang, C. Y., & Kuo, W. W. (2008). Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart. Molecular and Cellular Biochemistry, 311(1-2), 179-187. https://doi.org/10.1007/s11010-008-9708-6