title: The expression of macrophage migration inhibitory factor 1alpha (MIF 1alpha) in human atherosclerotic plaques is induced by different proatherogenic stimuli and associated with plaque instability.
abstract: OBJECTIVE
  Macrophage migration inhibitory factor 1alpha (MIF), a cytokine with immunoregulatory functions has been suggested to be involved in atherosclerotic plaque development. However, little is known about MIF-inducing conditions in the atherosclerotic process and the association of MIF with plaque instability.
  
  
  RESULTS
  Forty-two carotid endatherectomy samples from 36 patients and 4 aortic samples from young accident victims (as healthy controls) were analyzed for MIF staining. MIF expressing tissues in the atherosclerotic plaques are mainly mononuclear cells (MNCs), but also endothelial cells of intimal microvessels (MVECs). The magnitude and the intensity of their MIF expression was associated with the progression of plaques from early lesions (Stary I-III) to complicated plaque stages (Stary IV-VIII). In highly inflammatory and neovascularized regions of the plaques the colocalization of MIF expressing MNCs with CD40-L+ and angiotensin II (Ang II)-producing MNCs could be established. This finding supports the notion that CD40-L fusion protein and Ang II are able to induce MIF production in the monocytic cell line THP-1. Furthermore hypoxia (< or =1% O2) as a further proinflammatory and especially proangiogenetic factor was able to stimulate MIF secretion by THP-1, human monocytes and HUVECs. Hyperglycemia and insulin remained without effect.
  
  
  CONCLUSIONS
  MIF is expressed in advanced atherosclerotic lesions in close correlation with signs of instability, such as mononuclear cell inflammation and neointimal microvessel formation. Furthermore, the colocalization of MIF with Ang II-producing MNCs and CD40-L+ cells in these plaques and the finding that proathero- and -angiogenic mediators such as CD40-L, Ang II and hypoxia are able to stimulate MIF expression in vitro suggest an important role of MIF in the modulation of atherosclerotic plaque stability.
authors.affiliation: Medical Clinic II, Department of Cardiology, University of Technology Dresden, PO Box 95, Fetscherstr. 74, 01307 Dresden, Germany. alexanderschmeis@t-online.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmeisser
authors.forename: Rainer
authors.initials: R
authors.lastname: Marquetant
authors.forename: Thomas
authors.initials: T
authors.lastname: Illmer
authors.forename: Christiane
authors.initials: C
authors.lastname: Graffy
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
authors.forename: Dittmar
authors.initials: D
authors.lastname: Böckler
authors.forename: Dittmar
authors.initials: D
authors.lastname: Menschikowski
authors.forename: Ruediger
authors.initials: R
authors.lastname: Braun-Dullaeus
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D001167:Arteritis / Q000378:metabolism / Q000473:pathology; D023201:CD40 Ligand / Q000494:pharmacology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D015687:Cell Hypoxia; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D002537:Intracranial Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D007328:Insulin; D008263:Macrophage Migration-Inhibitory Factors; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D000804:Angiotensin II; D023201:CD40 Ligand; D005947:Glucose