This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 101/4/348    most recent CIRCRESAHA.106.147256v2 CIRCRESAHA.106.147256v1 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 Koga, M. Articles by Imaizumi, T. Search for Related Content PubMed PubMed Citation Articles by Koga, M. Articles by Imaizumi, T. Related Collections Pathophysiology Other arteriosclerosis Growth factors/cytokines Gene therapy Related Article

(Circulation Research. 2007;101:348.)
© 2007 American Heart Association, Inc.

Molecular Medicine

Inhibition of Progression and Stabilization of Plaques by Postnatal Interferon- Function Blocking in ApoE-Knockout Mice

Mitsuhisa Koga, Hisashi Kai, Hideo Yasukawa, Tomoka Yamamoto, Yumiko Kawai, Seiya Kato, Ken Kusaba, Mamiko Kai, Kensuke Egashira, Yasufumi Kataoka, Tsutomu Imaizumi

From the Department of Internal Medicine, Division of Cardiovascular Medicine (M. Koga, H.K., T.Y., Y. Kawai, K.K., T.I.), Kurume University; the Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences (M. Koga, T.Y., Y.K., M. Kai, Y. Kataoka), Fukuoka University; the Cardiovascular Research Institute (H.Y.) and the Department of Pathology (S.K.), Kurume University; 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 Cardiovascular Medicine, Kurume University, 67 Asahi-machi, Kurume 830-0011, Japan. E-mail naikai{at}med.kurume-u.ac.jp

A role of interferon- is suggested in early development of atherosclerosis. However, the role of interferon- in progression and destabilization of advanced atherosclerotic plaques remains unknown. Thus, the aim of this study was to determine whether postnatal inhibition of interferon- signaling could inhibit progression of atherosclerotic plaques and stabilize the lipid- and macrophage-rich advanced plaques. Atherosclerotic plaques were induced in ApoE-knockout (KO) mice by feeding high-fat diet from 8 weeks old (w). Interferon- function was postnatally inhibited by repeated gene transfers of a soluble mutant of interferon- receptors (sIFNR), an interferon- inhibitory protein, into the thigh muscle every 2 weeks. When sIFNR treatment was started at 12 w (atherosclerotic stage), sIFNR not only prevented plaque progression but also stabilized advanced plaques at 16 w: sIFNR decreased accumulations of the lipid and macrophages and increased fibrotic area with more smooth muscle cells. Moreover, sIFNR downregulated expressions of proinflammatory cytokines, chemokines, adhesion molecules, and matrix metalloproteinases but upregulated procollagen type I. sIFNR did not affect serum cholesterol levels. In conclusion, postnatal blocking of interferon- function by sIFNR treatment would be a new strategy to inhibit plaque progression and to stabilize advanced plaques through the antiinflammatory effects.

Key Words: atherosclerosis • inflammation • cytokine • gene therapy

Related Article:

Targeting Interferon- to Treat Atherosclerosis

Israel Gotsman and Andrew H. Lichtman
Circ. Res. 2007 101: 333-334. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				D. J. Schneider and H. S. Taatjes-Sommer Augmentation of Megakaryocyte Expression of Fc{gamma}RIIa by Interferon {gamma} Arterioscler. Thromb. Vasc. Biol., July 1, 2009; 29(7): 1138 - 1143. [Abstract] [Full Text] [PDF]

				R. Kleemann, S. Zadelaar, and T. Kooistra Cytokines and atherosclerosis: a comprehensive review of studies in mice Cardiovasc Res, August 1, 2008; 79(3): 360 - 376. [Abstract] [Full Text] [PDF]