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

Yao Zhong Kong, Xiao Ru Huang, Xiaosen Ouyang, Jei Ju Tan, Gunter Fingerle-Rowson, Michael Bacher, Wei Mu, Larry A. Scher, Lin Leng, Richard Bucala, Hui Y. Lan

Research output: Contribution to journalArticle

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Abstract

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. 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. 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). 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.

Original languageEnglish (US)
Pages (from-to)272-282
Number of pages11
JournalCardiovascular Research
Volume65
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

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Macrophage Migration-Inhibitory Factors
Matrix Metalloproteinase 1
Atherosclerotic Plaques
Blood Vessels
Proteins
Vascular Smooth Muscle
Smooth Muscle Myocytes
Immunohistochemistry
Cell Movement
Atherosclerosis
Up-Regulation
Color

Keywords

  • Atherosclerosis
  • Cytokines (MIF)
  • Macrophages
  • Matrix metalloproteinases
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Kong, Y. Z., Huang, X. R., Ouyang, X., Tan, J. J., Fingerle-Rowson, G., Bacher, M., ... Lan, H. Y. (2005). Evidence for vascular macrophage migration inhibitory factor in destabilization of human atherosclerotic plaques. Cardiovascular Research, 65(1), 272-282. https://doi.org/10.1016/j.cardiores.2004.09.020

Evidence for vascular macrophage migration inhibitory factor in destabilization of human atherosclerotic plaques. / Kong, Yao Zhong; Huang, Xiao Ru; Ouyang, Xiaosen; Tan, Jei Ju; Fingerle-Rowson, Gunter; Bacher, Michael; Mu, Wei; Scher, Larry A.; Leng, Lin; Bucala, Richard; Lan, Hui Y.

In: Cardiovascular Research, Vol. 65, No. 1, 01.01.2005, p. 272-282.

Research output: Contribution to journalArticle

Kong, YZ, Huang, XR, Ouyang, X, Tan, JJ, Fingerle-Rowson, G, Bacher, M, Mu, W, Scher, LA, Leng, L, Bucala, R & Lan, HY 2005, 'Evidence for vascular macrophage migration inhibitory factor in destabilization of human atherosclerotic plaques', Cardiovascular Research, vol. 65, no. 1, pp. 272-282. https://doi.org/10.1016/j.cardiores.2004.09.020
Kong, Yao Zhong ; Huang, Xiao Ru ; Ouyang, Xiaosen ; Tan, Jei Ju ; Fingerle-Rowson, Gunter ; Bacher, Michael ; Mu, Wei ; Scher, Larry A. ; Leng, Lin ; Bucala, Richard ; Lan, Hui Y. / Evidence for vascular macrophage migration inhibitory factor in destabilization of human atherosclerotic plaques. In: Cardiovascular Research. 2005 ; Vol. 65, No. 1. pp. 272-282.
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AU - Kong, Yao Zhong

AU - Huang, Xiao Ru

AU - Ouyang, Xiaosen

AU - Tan, Jei Ju

AU - Fingerle-Rowson, Gunter

AU - Bacher, Michael

AU - Mu, Wei

AU - Scher, Larry A.

AU - Leng, Lin

AU - Bucala, Richard

AU - Lan, Hui Y.

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N2 - 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. 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. 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). 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.

AB - 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. 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. 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). 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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KW - Macrophages

KW - Matrix metalloproteinases

KW - Smooth muscle cells

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