Published online before print January 29, 2004, doi: 10.1161/01.ATV.0000119356.35748.9e
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Vascular Biology |
Evidence for a Role of Macrophage Migration Inhibitory Factor in Vascular Disease
From the Cardiovascular Division (Z.C., M.S., A.C.Z., X.Z., C.S., D.I.S.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and Yale University School of Medicine (L.L., Y.M., R.B.), New Haven, Conn.
Correspondence to Dr Daniel I. Simon, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street Tower 3, Boston, MA 02115. E-mail dsimon{at}rics.bwh.harvard.edu
Objective— Inflammation plays an essential role in atherosclerosis and restenosis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is widely expressed in vascular cells. However, there is no in vivo evidence that MIF participates directly in vascular injury and repair. Therefore, we investigated the effect of MIF blockade on the response to experimental angioplasty in atherosclerosis-susceptible mice.
Methods and Results— Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDL receptor-deficient mice treated with a neutralizing anti-MIF or isotype control monoclonal antibody. After 7 days and 28 days, intimal and medial sizes were measured and intima/media area ratio (I/M) was calculated. Intimal thickening and I/M were reduced significantly by anti-MIF compared with control antibody. Vascular injury was accompanied by progressive vessel enlargement or "positive remodeling" that was comparable in both treatment groups. MIF blockade was associated with reduced inflammation and cellular proliferation and increased apoptosis after injury.
Conclusion— Neutralizing MIF bioactivity after experimental angioplasty in atherosclerosis-susceptible mice reduces vascular inflammation, cellular proliferation, and neointimal thickening. Although the molecular mechanisms responsible for these effects are not yet established, these data prompt further research directed at understanding the role of MIF in vascular disease and suggest novel therapeutic interventions for preventing atherosclerosis and restenosis.
Key Words: inflammation • cytokine • macrophage • atherosclerosis • restenosis
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 A. Zernecke, J. Bernhagen, and C. Weber Macrophage Migration Inhibitory Factor in Cardiovascular Disease Circulation, March 25, 2008; 117(12): 1594 - 1602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kwaijtaal, A. J. van der Ven, R. van Diest, C. A. Bruggeman, F. W. H. M. Bar, T. Calandra, A. Appels, and F. C. G. J. Sweep Exhaustion is Associated With Low Macrophage Migration Inhibitory Factor Expression in Patients With Coronary Artery Disease Psychosom Med, January 1, 2007; 69(1): 68 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Herder, H. Kolb, W. Koenig, B. Haastert, S. Muller-Scholze, W. Rathmann, R. Holle, B. Thorand, and H.-E. Wichmann Association of Systemic Concentrations of Macrophage Migration Inhibitory Factor With Impaired Glucose Tolerance and Type 2 Diabetes: Results from the Cooperative Health Research in the Region of Augsburg, Survey 4 (KORA S4) Diabetes Care, February 1, 2006; 29(2): 368 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Raines and N. Ferri Thematic Review Series: The Immune System and Atherogenesis. Cytokines affecting endothelial and smooth muscle cells in vascular disease J. Lipid Res., June 1, 2005; 46(6): 1081 - 1092. [Abstract] [Full Text] [PDF]
|
|