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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein
Jie-Hong Pan1, Galina K Sukhova, Jing-Tian Yang
1Department of Medicine, University of California San Francisco, Calif, USA.
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.
Methods And 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.
Insights
Macrophage migration inhibitory factor (MIF) deficiency significantly reduces atherosclerosis development and lesion severity in mice. This finding highlights MIF
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine found in vascular cells.
- In vivo evidence for MIF's role in atherogenesis is limited.
- The study investigates MIF's impact on atherosclerosis in a mouse model.
Purpose of the Study:
- To determine if MIF deficiency affects the formation and composition of atherosclerotic lesions.
- To explore the role of MIF in the inflammatory processes underlying atherosclerosis.
Main Methods:
- Generated Macrophage migration inhibitory factor knockout low-density lipoprotein receptor-deficient (MIF-/-LDLr-/-) mice.
- Fed mice an atherogenic diet for 12 or 26 weeks.
- Analyzed atherosclerotic lesion development, composition, and smooth muscle cell activity.
Main Results:
- MIF-/-LDLr-/- mice exhibited reduced abdominal aorta lipid deposition and intimal thickening.
- Atherosclerosis progression was slower in MIF-deficient mice, with decreased lesion cell proliferation.
- MIF deficiency reduced smooth muscle cell proliferation, protease expression, and matrix-degrading activities in mouse aortae.
Conclusions:
- MIF deficiency significantly attenuates atherogenesis in LDLr-/- mice.
- These findings offer new insights into inflammatory pathways in atheromata.
- MIF emerges as a potential therapeutic target for modulating atherosclerosis.

