Macrophage migration inhibitory factor is associated with aneurysmal expansion.
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.
Pan
Jie-Hong
JH
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California-San Francisco, 90 Medical Center Way, San Francisco, CA 94143, USA.
Lindholt
Jes S
JS
Sukhova
Galina K
GK
Baugh
John A
JA
Henneberg
Eskild W
EW
Bucala
Richard
R
Donnelly
Seamas C
SC
Libby
Peter
P
Metz
Christine
C
Shi
Guo-Ping
GP
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
D008263:Macrophage Migration-Inhibitory Factors