title: Macrophage migration inhibitory factor is associated with aneurysmal expansion.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions.
  
  
  METHODS
  MIF immunohistochemistry was performed on tissue sections from five normal aortas, seven atherosclerotic carotids, and six AAAs. A group of 112 men with small AAAs (defined as 3 to 5 cm) was recruited at the time of diagnosis, had serum samples taken, and was followed annually for 1 to 5 years (mean, 2.9 years) and referred for surgery if the AAA exceeded 5 cm in diameter. Of this study group, 98 had serum MIF measured with an enzyme-linked immunosorbent assay and 61 had detectable levels.
  
  
  RESULTS
  In human atherosclerotic and aneurysmal lesions, MIF protein colocalized in macrophages, endothelial cells, and smooth muscle cells, but normal arteries had negligible MIF expression. Furthermore, serum-MIF levels correlated significantly with annual expansion rate (r = 0.28; P =.005), persisting after adjustment for initial AAA size, smoking habits, diastolic blood pressure, ankle blood pressure index, and age. After exclusion of 38 cases with MIF levels below the detection limit, initial AAA size was also significantly correlated with the MIF levels (r = 0.42; P =.001), persisting after adjustment for similar confounders, and the correlation coefficient with expansion rate increased to 0.42 (P =.001).
  
  
  CONCLUSIONS
  Highly expressed MIF in macrophages, endothelial cells, and smooth muscle cells in lesions from atherosclerosis and AAA and significant association between serum MIF level and AAA initial size and AAA expansion rate in a group of patients with AAA suggest a potential involvement of this proinflammatory cytokine in the pathogenesis of these cardiovascular diseases.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California-San Francisco, 90 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Jie-Hong
authors.initials: JH
authors.lastname: Pan
authors.forename: Jes S
authors.initials: JS
authors.lastname: Lindholt
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.forename: John A
authors.initials: JA
authors.lastname: Baugh
authors.forename: Eskild W
authors.initials: EW
authors.lastname: Henneberg
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Christine
authors.initials: C
authors.lastname: Metz
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000368:Aged; D001011:Aorta / Q000737:chemistry; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000737:chemistry; D002340:Carotid Artery Diseases / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry
chemical_list: D008263:Macrophage Migration-Inhibitory Factors