Published online before print March 11, 2002, doi: 10.1161/01.CIR.0000012942.49244.82
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(Circulation. 2002;105:1561.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Expression of Macrophage Migration Inhibitory Factor in Different Stages of Human Atherosclerosis
From the Laboratory of Biochemistry, Institute for Interfacial Engineering, University of Stuttgart, Stuttgart, Germany (A.B.-K., J.B.); the Department of Pathology, University of Freiburg, Freiburg, Germany (H.G., H.E.S., C.I.); the Department of Vascular Surgery, University of Innsbruck, Innsbruck, Austria (R.S., G.F.); the Division of Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany (S.D.); and the Gaubius Laboratory, Netherlands Organization for Applied Scientific Research–Prevention and Health, Leiden, the Netherlands (R.K.).
Correspondence to Christian Ihling, MD, Department of Pathology, University of Freiburg, Albertstraße 19, D-79104 Freiburg, Germany. E-mail cihling{at}gmx.de
Background— Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. Macrophage migration inhibitory factor (MIF), a cytokine with potent inflammatory functions, was thus considered to be important in atherosclerotic lesion evolution.
Methods and Results— We studied the presence and distribution of MIF immunoreactivity (MIF-IR) and MIF mRNA in internal mammary arteries with a normal histology and arteries with plaques in different stages of human atherosclerosis. To address a potential role for the coactivator Jab1 as a cellular mediator of MIF effects in vascular tissue, we correlated the expression of MIF to that of Jab1 by using immunohistochemistry and coimmunoprecipitation. We further sought to determine a potential functional role for endothelium-derived MIF in early atherogenesis by studying the effects of oxidized LDL on MIF expression in cultured human umbilical vascular endothelial cells. The results showed that MIF-IR and Jab1-IR are found in all cell types present in atherosclerotic lesions, that MIF-IR is upregulated during progression of atherosclerosis, that MIF is produced locally in the arterial wall, and that all MIF+ cells are simultaneously Jab1+. Coimmunoprecipitation experiments demonstrated in vivo complex formation between MIF and Jab1 in plaques. MIF expression in human umbilical vascular endothelial cells and a macrophage line was upregulated after stimulation with oxidized LDL.
Conclusions— MIF is produced abundantly by various cells in all types of human atherosclerotic lesions and thus may play an important role in early plaque development and advanced complicated lesions. MIF-Jab1 complexes could serve critical regulatory functions in atherosclerotic lesion evolution.
Key Words: lesion • atherosclerosis • inflammation • pathology
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