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(Circulation Research. 2001;88:e31.)
© 2001 American Heart Association, Inc.

Letter to the Editor

Letter to the Editor

Masafumi Takahashi¹

¹ Department of Cardiology, Jichi Medical School, Tochigi, Japan, masafumi@jichi.ac.jp

Jun Nishihira²

² Central Research Institute, Hokkaido University, Sapporo, Japan

Yuichi Takahashi³

³ Tohoku Kohsei Nenkin Hospital, Sendai, Japan

Uichi Ikeda⁴

⁴

Kazuyuki Shimada⁵

⁵ Department of Cardiology, Jichi Medical School, Tochigi, Japan

	De Novo Expression of Macrophage Migration Inhibitory Factor in Atherogenesis

 
To the Editor:

We read with great interest the article by Lin et al¹ on the expression of macrophage migration inhibitory factor (MIF) in atherosclerotic lesions of a hypercholesterolemic rabbit model. They demonstrated, in the early stages of atherogenesis, marked upregulation of MIF mRNA. The protein was detected in vascular endothelial cells with CD68-positive macrophages adhering to endothelial cells and subsequently migrating into the subendothelial space. However, MIF expression by smooth muscle cells was transient during atherogenesis. Interestingly, the accumulation of macrophages was exclusively localized to areas of strong MIF expression, which may be responsible for the development of foam cell–rich lesions in hypercholesterolemic rabbits.

We previously reported that MIF was expressed in macrophages² and endothelial cells.³ Furthermore, we recently investigated MIF expression in human atherectomy samples obtained from coronary and femoral arteries of patients with coronary and peripheral artery diseases. Strong MIF expression was localized in CD68-positive macrophages, whereas weak MIF expression was detected in -actin–positive smooth muscle cells of atherosclerotic lesions. These findings suggest that, as observed in a rabbit model by Lin et al,¹ macrophages are a major source of MIF expression in human atherosclerotic vessels, and upregulation of MIF expression by these cells may contribute to local macrophage accumulation, ultimately resulting in macrophage-rich atherosclerotic lesion formation in humans.

	References

 
1. Lin S-G, Yu X-Y, Chen Y-X, Huang X-R, Metz C, Bucala R, Lau C-P, Lan HY. De novo expression of macrophage migration inhibitory factor in atherogenesis in rabbits. Circ Res. 2000;87:1202–1208.[Abstract/Free Full Text]

2. Sakamoto W, Nishihira J, Fujie K, Handa H, Ozaki M, Yukawa S. Inhibition of macrophage migration inhibitory factor secretion from macrophages by vitamin E. Biochim Biophys Acta. 1998;1404:427-434.[Medline] [Order article via Infotrieve]

3. Nishihira J, Koyama Y, Mizue Y. Identification of macrophage migration inhibitory factor (MIF) in human vascular endothelial cells and its induction by lipopolysaccharide. Cytokine. 1998;10:199-205.[Medline] [Order article via Infotrieve]