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

Research output: Contribution to journalArticle

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

Fingerprint

Neointima
Interferons
Wounds and Injuries
Interferon Regulatory Factor-1
Intercellular Adhesion Molecule-1
Smooth Muscle Myocytes
Blood Vessels
Plasmids
Interferon Receptors
STAT1 Transcription Factor
Tunica Intima
Platelet-Derived Growth Factor Receptors
Platelet-Derived Growth Factor
Thigh
Wistar Rats
Proteins
Transcription Factors
Up-Regulation
Phosphorylation
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Kusaba, K., Kai, H., Koga, M., Takayama, N., Ikeda, A., Yasukawa, H., ... 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

Inhibition of intrinsic interferon-γ function prevents neointima formation after balloon injury. / Kusaba, Ken; Kai, Hisashi; Koga, Mitsuhisa; Takayama, Narimasa; Ikeda, Ayami; Yasukawa, Hideo; Seki, Yukihiko; Egashira, Kensuke; Imaizumi, Tsutomu.

In: Hypertension, Vol. 49, No. 4, 01.04.2007, p. 909-915.

Research output: Contribution to journalArticle

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, vol. 49, no. 4, pp. 909-915. https://doi.org/10.1161/01.HYP.0000259668.37901.8c
Kusaba, Ken ; Kai, Hisashi ; Koga, Mitsuhisa ; Takayama, Narimasa ; Ikeda, Ayami ; Yasukawa, Hideo ; Seki, Yukihiko ; Egashira, Kensuke ; Imaizumi, Tsutomu. / Inhibition of intrinsic interferon-γ function prevents neointima formation after balloon injury. In: Hypertension. 2007 ; Vol. 49, No. 4. pp. 909-915.
@article{c5c256a75b44487ea5fa8de7f3d79ae0,
title = "Inhibition of intrinsic interferon-γ function prevents neointima formation after balloon injury",
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.",
author = "Ken Kusaba and Hisashi Kai and Mitsuhisa Koga and Narimasa Takayama and Ayami Ikeda and Hideo Yasukawa and Yukihiko Seki and Kensuke Egashira and Tsutomu Imaizumi",
year = "2007",
month = "4",
day = "1",
doi = "10.1161/01.HYP.0000259668.37901.8c",
language = "English",
volume = "49",
pages = "909--915",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Inhibition of intrinsic interferon-γ function prevents neointima formation after balloon injury

AU - Kusaba, Ken

AU - Kai, Hisashi

AU - Koga, Mitsuhisa

AU - Takayama, Narimasa

AU - Ikeda, Ayami

AU - Yasukawa, Hideo

AU - Seki, Yukihiko

AU - Egashira, Kensuke

AU - Imaizumi, Tsutomu

PY - 2007/4/1

Y1 - 2007/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34047219787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047219787&partnerID=8YFLogxK

U2 - 10.1161/01.HYP.0000259668.37901.8c

DO - 10.1161/01.HYP.0000259668.37901.8c

M3 - Article

C2 - 17309951

AN - SCOPUS:34047219787

VL - 49

SP - 909

EP - 915

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 4

ER -