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(Circulation. 2008;117:1594-1602.)
© 2008 American Heart Association, Inc.

Basic Science for Clinicians

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

Alma Zernecke, MD; Jürgen Bernhagen, PhD; Christian Weber, MD

From the Institute for Molecular Cardiovascular Research (A.Z., C.W.) and Department of Biochemistry and Molecular Cell Biology (J.B.), Molekulare Herz-Kreislaufforschung, RWTH Aachen University, Aachen, Germany.

Correspondence to Dr Christian Weber, Institut für Molekulare Herz-Kreislaufforschung, Universitätsklinikum der RWTH Aachen, Pauwelsstraβe 30, 52074 Aachen, Germany (e-mail cweber{at}ukaachen.de); or Dr Jürgen Bernhagen, Institut für Biochemie, Universitätsklinikum der RWTH Aachen, Pauwelsstraβe 30, 52074 Aachen, Germany (e-mail jbernhagen@ukaachen.de).

The highly conserved and archetypical yet atypical cytokine macrophage migration inhibitory factor (MIF) fulfills pleiotropic immune functions in many acute and chronic inflammatory diseases. Recent evidence has emerged from both expression and functional studies to implicate MIF in various aspects of cardiovascular disease. The present review is aimed at providing a synopsis of the involvement of MIF in the inflammatory pathogenesis of atherosclerosis and its consequences, namely unstable plaque formation, remodeling after arterial injury, aneurysm formation, myocardial infarction, or ischemia-reperfusion injury. In addition, other forms of myocardial dysfunction and inflammation and the role of MIF in angiogenesis are reviewed. The functional data are reconciled with recent progress in the identification of heptahelical (CXC chemokine) receptors for MIF, its prototypic role as their noncanonical ligand, and its signal transduction profile operative in atherogenic and inflammatory recruitment of mononuclear cells and in the oxidative damage and apoptosis of cardiomyocytes. Its unique features and functions clearly distinguish MIF from other cytokines implicated in atherogenesis and make it a prime target for achieving therapeutic regression of atherosclerosis. The potential of targeting or exploiting MIF for therapeutic strategies or as a diagnostic marker in the management of cardiovascular diseases or disorders is scrutinized.

Key Words: atherosclerosis • cytokines • inflammation • myocardium • remodeling

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