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Published on: October 17, 2017
Evidence for vascular macrophage migration inhibitory factor in destabilization of human atherosclerotic plaques
Yao-Zhong Kong1, Xiao-Ru Huang, Xiaosen Ouyang
1The First People's Foshan Hospital, Foshan, Guangdong, China.
Objective:
Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and has been shown to play a role in pathogenesis of atherosclerosis. The aim of this study is to investigate the potential role of MIF in the destabilization of atherosclerotic plaques by stimulation of vascular MMP-1 expression.
Methods:
MIF and matrix metalloproteinase protein-1 (MMP-1) expression in human atherosclerotic plaques were determined by immunohistochemistry. The functional activity of MIF was examined by its ability to induce MMP-1 expression in vascular smooth muscle cells (VSMCs) in vitro.
Results:
Two-color immunohistochemistry demonstrated that MIF was strongly upregulated in vulnerable, but not in fibrous plaques. Upregulation of vascular MIF was associated with macrophage accumulation (p<0.01), strong expression of vascular MMP-1 (p<0.001), and collagenolysis in vulnerable atheromatous plaques, but not in the fibrous lesions. Co-expression of MIF and MMP-1 in vulnerable atheromatous plaques appeared to contribute to the weakening of fibrous caps and plaque disruption. The role of MIF in vascular MMP-1 expression was demonstrated by the ability of MIF to directly stimulate VSMCs to express MMP-1 mRNA and protein, and to increase MMP-1 activity in a dose- and time-dependent manner, which was blocked by a neutralizing MIF antibody (p<0.001).
Conclusions:
MIF and MMP-1 are markedly upregulated in vulnerable atheromatous plaques and are associated with the weakening of the fibrous cap. The ability of MIF to induce MMP-1 expression and collagenolytic activity in VSMCs suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.
Insights
Macrophage migration inhibitory factor (MIF) and matrix metalloproteinase-1 (MMP-1) are elevated in vulnerable atherosclerotic plaques, contributing to plaque weakening. MIF directly stimulates MMP-1 expression, suggesting a role in plaque destabilization.
Area of Science:
- Cardiovascular Biology
- Immunology
- Pathology
Background:
- Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in atherosclerosis pathogenesis.
- Atherosclerotic plaque destabilization is a critical event leading to cardiovascular events.
Purpose of the Study:
- To investigate the role of MIF in atherosclerotic plaque destabilization.
- To examine the effect of MIF on vascular matrix metalloproteinase-1 (MMP-1) expression.
Main Methods:
- Immunohistochemistry was used to assess MIF and MMP-1 expression in human atherosclerotic plaques.
- In vitro studies utilized vascular smooth muscle cells (VSMCs) to determine MIF's functional activity on MMP-1 induction.
Main Results:
- MIF and MMP-1 were significantly upregulated in vulnerable plaques, correlating with macrophage infiltration and collagenolysis.
- MIF directly stimulated VSMCs to increase MMP-1 mRNA, protein, and activity in a dose- and time-dependent manner.
- MIF-induced MMP-1 expression and activity were inhibited by a neutralizing MIF antibody.
Conclusions:
- MIF and MMP-1 are key players in the weakening of fibrous caps in vulnerable atherosclerotic plaques.
- MIF's ability to induce MMP-1 suggests a significant role in the destabilization of human atherosclerotic plaques.
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