Stimulation of vascular smooth muscle cell migration by macrophage migration inhibitory factor
B H G J Schrans-Stassen1, H Lue, D G P Sonnemans
1The Interuniversity Cardiology Institute of The Netherlands, Cardiovascular Research Institute Maastricht, Department of Molecular and Experimental Cardiology, Maastricht, The Netherlands.
Abstract:
Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor that influences the migration and proliferation of various cell types, predominantly monocytes and macrophages. Recent evidence suggests an important role for MIF in the progression of atherosclerosis and restenosis. For this reason, we studied the effect of MIF on platelet-derived growth factor-BB (PDGF-BB)-induced migration and PDGF receptor protein expression in vascular smooth muscle cells (VSMCs). Furthermore, the possibility of MIF influencing the migration of VSMCs was investigated. Our results show that short-term incubation of MIF is able to enhance PDGF-BB-induced migration. Long-term incubation decreases PDGF-BB-induced migration, but preserves a short-term stimulatory effect. These effects are not regulated at the level of PDGF receptor protein expression. MIF also acts as a chemoattractant for VSMCs, with a maximum response at 15 ng/ml. In contrast, the proliferation of VSMCs was unaffected by MIF. We conclude that MIF has a biphasic effect on VSMC migration. It remains unclear whether this effect is direct or involves the secretion of unidentified promigratory factors. Exogenous MIF does not stimulate VSMC proliferation; however, a role for MIF in proliferation cannot be fully ruled out. In view of the known key contributions of macrophage-derived MIF and VSMCs, the observed effects may well play a role in the progression of atherosclerosis and restenosis.
Insights
Macrophage migration inhibitory factor (MIF) influences vascular smooth muscle cell (VSMC) migration in a biphasic manner, potentially impacting atherosclerosis and restenosis progression.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Biology
Background:
- Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator.
- MIF is implicated in the pathogenesis of atherosclerosis and restenosis.
- Vascular smooth muscle cells (VSMCs) play critical roles in these conditions.
Purpose of the Study:
- To investigate the effect of MIF on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC migration.
- To examine MIF's influence on PDGF receptor protein expression in VSMCs.
- To determine if MIF acts as a chemoattractant for VSMCs.
Main Methods:
- Short-term and long-term incubation of VSMCs with MIF.
- Assessment of PDGF-BB-induced VSMC migration.
- Analysis of PDGF receptor protein expression.
- Chemotaxis assays to evaluate VSMC migration towards MIF.
Main Results:
- Short-term MIF exposure enhanced PDGF-BB-induced VSMC migration.
- Long-term MIF exposure reduced PDGF-BB-induced migration but retained a short-term stimulatory effect.
- MIF acted as a chemoattractant for VSMCs, with optimal response at 15 ng/ml.
- MIF did not affect VSMC proliferation, and PDGF receptor expression was not altered.
Conclusions:
- MIF exhibits a biphasic effect on VSMC migration, potentially contributing to atherosclerosis and restenosis.
- The precise mechanisms of MIF's migratory effects require further elucidation.
- MIF does not directly stimulate VSMC proliferation, though a role cannot be entirely excluded.
