This Article Full Text Full Text (PDF) 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 Google Scholar Google Scholar Articles by Gotsman, I. Articles by Lichtman, A. H. Search for Related Content PubMed PubMed Citation Articles by Gotsman, I. Articles by Lichtman, A. H. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Genes and Gene Therapy Related Collections Related Article

(Circulation Research. 2007;101:333.)
© 2007 American Heart Association, Inc.

Editorials

Targeting Interferon- to Treat Atherosclerosis

Israel Gotsman, Andrew H. Lichtman

From the Heart Institute (I.G.), Hadassah University Hospital, Jerusalem, Israel; and Immunology and Vascular Research Divisions (A.H.L.), Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Andrew H. Lichtman, MD, PhD, Department of Pathology, Brigham and Women’s Hospital, 77 Ave Louis Pasteur, NRB 752N, Boston, MA 02115. E-mail lichtman@rics.bwh.harvard.edu

See related article, pages 348–356

Key Words: atherosclerosis • cytokines • interferon- • gene therapy

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The chronic inflammatory nature of atherosclerotic disease is now widely appreciated. Abnormal deposition and oxidative modification of serum lipoproteins in arterial walls stimulates the recruitment of monocytes and their conversion into foam cells. Concurrently, both innate and adaptive immune responses are induced. Cytokines and growth factors produced as part of these responses lead to the remodeling of the arterial wall that typifies atherosclerotic lesions, including SMC accumulation and collagenous matrix deposition in the intima.¹ The predominant inflammatory cells found in the atherosclerotic plaques are macrophages and T lymphocytes.² The majority of T lymphocytes in atherosclerotic lesions are CD4⁺ T-helper cells expressing markers of activation.³ These activated T lymphocytes have been shown to be important in propagating the inflammatory processes that enhance lesion development.^4,5 The majority of these T cells have a phenotype characteristic of the proinflammatory T-helper 1 (Th1) subset, and Th1-mediated immune responses have been shown to correlate with the development of atherosclerosis in mouse models.^6–8

The signature cytokine produced by Th1 cells is interferon (IFN). Immunohistochemical and in situ hybridization studies indicate that IFN is present in human atherosclerotic plaques.^2,9–11 Numerous studies in mice have demonstrated a central role of IFN in atherosclerosis. Genetic ablation of IFN or IFN receptor (IFNR) expression in mice significantly reduces atherosclerosis,^12,13 whereas administration of exogenous IFN potentiates atherosclerosis.¹⁴ IFN has many different biologic effects that contribute to lesion development, including enhancement of antigen presenting capabilities of endothelium and macrophages, enhancement of inflammatory cell recruitment via upregulation of endothelial adhesion molecules, . . . [Full Text of this Article]

Related Article:

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, and Tsutomu Imaizumi
Circ. Res. 2007 101: 348-356. [Abstract] [Full Text] [PDF]