This Article Full Text Full Text (PDF) All Versions of this Article: 49/4/909    most recent 01.HYP.0000259668.37901.8cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kusaba, K. Articles by Imaizumi, T. Search for Related Content PubMed PubMed Citation Articles by Kusaba, K. Articles by Imaizumi, T. Pubmed/NCBI databases Substance via MeSH Related Collections Pathophysiology Cell signalling/signal transduction Other arteriosclerosis Growth factors/cytokines Gene therapy

(Hypertension. 2007;49:909.)
© 2007 American Heart Association, Inc.

Original Articles

Inhibition of Intrinsic Interferon- 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

From the Department of Internal Medicine (K.K., H.K., M.K., N.T., A.I., Y.S., T.I.), Division of Cardio-vascular Medicine, Kurume University School of Medicine, Kurume, Japan; the Department of Pharmaceutical Care and Health Sciences (M.K.), Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; the Cardiovascular Research Institute (H.Y.), Kurume University, Kurume, Japan; and the Department of Cardiovascular Medicine (K.E.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Correspondence to Hisashi Kai, Department of Internal Medicine, Division of Cardio-vascular Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan. E-mail naikai{at}med.kurume-u.ac.jp

It is still controversial whether intrinsic interferon (IFN)- promotes or attenuates vascular remodeling in hyperproliferative vascular disorders, such as neointima formation after balloon injury. Thus, we investigated whether inhibition of intrinsic IFN- function prevents neointima formation. For this purpose, naked DNA plasmid encoding a soluble mutant of IFN- receptor -subunit (sIFNR; an IFN- inhibitory protein) or mock plasmid was injected into the thigh muscle of male Wistar rats 2 days before balloon injury (day –2). sIFNR gene transfer significantly elevated serum levels of sIFNR 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. sIFNR 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- signal). Balloon injury also upregulated the key molecules of neointima formation, such as intercellular adhesion molecule-1 and platelet-derived growth factor ß-receptor. These changes were suppressed by sIFNR treatment. In conclusion, it is suggested that intrinsic IFN- 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- signaling may be a new therapeutic target for prevention of neointima formation of hyperproliferative vascular disorders.

Key Words: IFN- • neointima • gene therapy • inflammation • signaling

This article has been cited by other articles:

				H. Kudo, H. Kai, H. Kajimoto, M. Koga, N. Takayama, T. Mori, A. Ikeda, S. Yasuoka, T. Anegawa, H. Mifune, et al. Exaggerated Blood Pressure Variability Superimposed on Hypertension Aggravates Cardiac Remodeling in Rats via Angiotensin II System-Mediated Chronic Inflammation Hypertension, October 1, 2009; 54(4): 832 - 838. [Abstract] [Full Text] [PDF]

				B. S. Fleenor and D. K. Bowles Exercise training decreases the size and alters the composition of the neointima in a porcine model of percutaneous transluminal coronary angioplasty (PTCA) J Appl Physiol, September 1, 2009; 107(3): 937 - 945. [Abstract] [Full Text] [PDF]

				H. Murayama, M. Takahashi, M. Takamoto, Y. Shiba, H. Ise, J. Koyama, Y.-i. Tagawa, Y. Iwakura, and U. Ikeda Deficiency of tumour necrosis factor-{alpha} and interferon-{gamma} in bone marrow cells synergistically inhibits neointimal formation following vascular injury Cardiovasc Res, November 1, 2008; 80(2): 175 - 180. [Abstract] [Full Text] [PDF]

				I. Gotsman and A. H. Lichtman Targeting Interferon-{gamma} to Treat Atherosclerosis Circ. Res., August 17, 2007; 101(4): 333 - 334. [Full Text] [PDF]