Inhibition of intrinsic interferon-γ function prevents neointima formation after balloon injury

Ken Kusaba, Hisashi Kai, Mitsuhisa Koga, Narimasa Takayama, Ayami Ikeda, Hideo Yasukawa, Yukihiko Seki, Kensuke Egashira, Tsutomu Imaizumi

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28 Citations (Scopus)

Abstract

It is still controversial whether intrinsic interferon (IFN)-γ promotes or attenuates vascular remodeling in hyperproliferative vascular disorders, such as neointima formation after balloon injury. Thus, we investigated whether inhibition of intrinsic IFN-γ function prevents neointima formation. For this purpose, naked DNA plasmid encoding a soluble mutant of IFN-γ receptor α-subunit (sIFNγR; an IFN-γ inhibitory protein) or mock plasmid was injected into the thigh muscle of male Wistar rats 2 days before balloon injury (day -2). sIFNγR gene transfer significantly elevated serum levels of sIFNγR protein for 2 weeks. In mock-treated rats, balloon injury induced smooth muscle cell proliferation in the neointima with a peak at day 7 and produced thick neointima at day 14. sIFNγR treatment reduced the number of proliferating intimal smooth muscle cells by 50% at day 7 and attenuated neointima formation with a 45% reduction of the intima/media area ratio at day 14. In mock-treated rats, at day 7, balloon injury induced phosphorylation of signal transducer and activator of transcription-1 and upregulations of IFN regulatory factor-1 (a transcription factor mediating IFN-γ signal). Balloon injury also upregulated the key molecules of neointima formation, such as intercellular adhesion molecule-1 and platelet-derived growth factor β-receptor. These changes were suppressed by sIFNγR treatment. In conclusion, it is suggested that intrinsic IFN-γ promotes neointima formation probably through IFN regulatory factor-1/intercellular adhesion molecule-1-mediated and platelet-derived growth factor-mediated mechanisms. Thus, inhibition of IFN-γ signaling may be a new therapeutic target for prevention of neointima formation of hyperproliferative vascular disorders.

Original languageEnglish
Pages (from-to)909-915
Number of pages7
JournalHypertension
Volume49
Issue number4
DOIs
Publication statusPublished - Apr 1 2007

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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    Kusaba, K., Kai, H., Koga, M., Takayama, N., Ikeda, A., Yasukawa, H., Seki, Y., Egashira, K., & Imaizumi, T. (2007). Inhibition of intrinsic interferon-γ function prevents neointima formation after balloon injury. Hypertension, 49(4), 909-915. https://doi.org/10.1161/01.HYP.0000259668.37901.8c