Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Biophysics

Background:

• Macrophage migration inhibitory factor (MIF) is implicated in inflammatory diseases like atherosclerosis.
• High MIF expression in leukocytes contributes to atherosclerosis initiation and progression.
• The role of biomechanical forces, specifically shear stress, in regulating MIF in endothelial cells (ECs) is largely unknown.

Purpose of the Study:

• To investigate the effect of different types of shear stress on MIF expression in endothelial cells.
• To elucidate the molecular mechanisms by which shear stress regulates MIF.
• To determine if MIF is a target of shear stress-mediated athero-protective pathways.

Main Methods:

• Transcriptome profiling of human coronary artery ECs under laminar shear stress (LS) and oscillatory shear stress (OS).
• En face staining of rabbit aorta to assess MIF immunoreactivity in vivo.
• Gene knockdown and overexpression studies of Krüpple like factor 2 (KLF2) in ECs.
• Analysis of MIF expression levels under varying shear stress conditions.

Main Results:

• LS significantly attenuates MIF expression in ECs, while OS increases it.
• High MIF immunoreactivity is observed in regions of the aorta prone to OS, such as bifurcations.
• KLF2 is essential for LS-induced inhibition of MIF expression; KLF2 knockdown abrogates this effect, while KLF2 overexpression reduces MIF levels.

Conclusions:

• MIF expression in ECs is sensitive to biomechanical shear stress.
• KLF2 acts as a key transcription factor mediating the inhibitory effect of LS on MIF.
• LS exerts athero-protective effects partly by directly suppressing pro-inflammatory MIF expression via KLF2.