Evidence for vascular macrophage migration inhibitory factor in destabilization of human atherosclerotic plaques.

Authors: Kong, YZ  Huang, XR  Ouyang, X  Tan, JJ  Fingerle-Rowson, G  Bacher, M  Mu, W  Scher, LA  Leng, L  Bucala, R  Lan, HY 
Citation: Kong YZ, etal., Cardiovasc Res. 2005 Jan 1;65(1):272-82.
Pubmed: (View Article at PubMed) PMID:15621056
DOI: Full-text: DOI:10.1016/j.cardiores.2004.09.020

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.


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RGD ID: 1582525
Created: 2006-11-13
Species: All species
Last Modified: 2006-11-13
Status: ACTIVE