title: Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine expressed widely by vascular cells. However, scant in vivo evidence supports direct participation of MIF in atherogenesis. Therefore, we investigated whether deficiency of MIF modulates atherosclerotic lesion formation and composition in low-density lipoprotein receptor-deficient (LDLr-/-) mice.
  
  
  RESULTS
  MIF-/-LDLr-/- and LDLr-/- mice were generated and consumed an atherogenic diet for 12 or 26 weeks. MIF-/-LDLr-/- mice had significantly reduced abdominal aorta lipid deposition and intimal thickening from aortic arch throughout the abdominal aorta compared with LDLr-/- mice. Marked retardation of atherosclerosis over time in MIF-deficient mice accompanied decreased lesion cell proliferation. At 26 weeks, 20% of MIF-deficient mice developed only early, fatty streak-like lesions, whereas >80% of LDLr-/- mice developed advanced lesions containing calcification and lipid cores. Analysis of smooth muscle cells from mouse aortae demonstrated that MIF deficiency reduced smooth muscle cell proliferation, cysteine protease expression, and elastinolytic and collagenolytic activities.
  
  
  CONCLUSIONS
  Deficiency of MIF reduces atherogenesis in LDLr-/- mice. These results provide novel insight into inflammatory pathways operating in atheromata and identify a new potential target for modulating atherogenesis.
authors.affiliation: Department of Medicine, University of California San Francisco, Calif, USA.
authors.forename: Jie-Hong
authors.initials: JH
authors.lastname: Pan
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.forename: Jing-Tian
authors.initials: JT
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.forename: Huanxiang
authors.initials: H
authors.lastname: Fu
authors.forename: Yaou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: John R
authors.initials: JR
authors.lastname: David
authors.forename: Christine N
authors.initials: CN
authors.lastname: Metz
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fang
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
authors.forename: Harold A
authors.initials: HA
authors.lastname: Chapman
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002455:Cell Division; D017364:Collagenases / Q000172:deficiency / Q000378:metabolism; D003433:Crosses, Genetic; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000378:metabolism; D004036:Diet, Atherogenic; D004790:Enzyme Induction; D020022:Genetic Predisposition to Disease; D019746:Intramolecular Oxidoreductases; D008055:Lipids / Q000032:analysis; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D010196:Pancreatic Elastase / Q000172:deficiency / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D008055:Lipids; D008263:Macrophage Migration-Inhibitory Factors; D011973:Receptors, LDL; D010196:Pancreatic Elastase; D003546:Cysteine Endopeptidases; D017364:Collagenases; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse