Macrophage migration inhibitory factor induces MMP-9 expression

Implications for destabilization of human atherosclerotic plaques

Yao Zhong Kong, Xiyong Yu, Jia Ju Tang, Xiaosen Ouyang, Xiao Ru Huang, Gunter Fingerle-Rowson, Michael Bacher, Larry A. Scher, Richard Bucala, Hui Y. Lan

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Macrophage migration inhibitory factor (MIF) has been shown to participate in both experimental and human atherogenesis. Expression of MMP-9 has been shown to play a role in the instability of atherosclerotic plaque. Thus, we hypothesize that MIF may participate in the destabilization of atherosclerotic plaques by stimulating MMP-9 expression. This hypothesis was investigated by examining the expression of MIF and MMP-9 in human atherosclerotic plaques using two-color immunostaining and by determining the potential role of MIF in the induction of MMP-9 expression in vascular smooth muscle cells (VSMC) and macrophages in vitro. Two-color immunohistochemistry demonstrated that MIF was strongly upregulated by macrophages and VSMCs. This was associated with marked increase in MMP-9 expression in vulnerable atheromatous plaques, but not in the fibrous lesions. Upregulation of MIF and MMP-9 in vulnerable atheromatous plaques was associated with the weakening of fibrous caps. The role of MIF in MMP-9 expression was demonstrated by the ability of MIF to directly induce MMP-9 mRNA and protein expression in macrophages and in VSMCs in a dose and time-dependent manner, which was blocked by a neutralizing MIF antibody. In conclusion, MIF and MMP-9 are markedly upregulated in vulnerable atheromatous plaques. The ability of MIF to induce MMP-9 expression in VSMCs and macrophages suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.

Original languageEnglish (US)
Pages (from-to)207-215
Number of pages9
JournalAtherosclerosis
Volume178
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Macrophage Migration-Inhibitory Factors
Atherosclerotic Plaques
Matrix Metalloproteinases
Macrophages
Color
Vascular Smooth Muscle
Smooth Muscle Myocytes
Atherosclerosis
Up-Regulation
Immunohistochemistry

Keywords

  • Atherosclerosis
  • Macrophages
  • MIF
  • MMP-9
  • Plaque instability
  • VSMCs

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Macrophage migration inhibitory factor induces MMP-9 expression : Implications for destabilization of human atherosclerotic plaques. / Kong, Yao Zhong; Yu, Xiyong; Tang, Jia Ju; Ouyang, Xiaosen; Huang, Xiao Ru; Fingerle-Rowson, Gunter; Bacher, Michael; Scher, Larry A.; Bucala, Richard; Lan, Hui Y.

In: Atherosclerosis, Vol. 178, No. 1, 01.2005, p. 207-215.

Research output: Contribution to journalArticle

Kong, YZ, Yu, X, Tang, JJ, Ouyang, X, Huang, XR, Fingerle-Rowson, G, Bacher, M, Scher, LA, Bucala, R & Lan, HY 2005, 'Macrophage migration inhibitory factor induces MMP-9 expression: Implications for destabilization of human atherosclerotic plaques', Atherosclerosis, vol. 178, no. 1, pp. 207-215. https://doi.org/10.1016/j.atherosclerosis.2004.08.030
Kong, Yao Zhong ; Yu, Xiyong ; Tang, Jia Ju ; Ouyang, Xiaosen ; Huang, Xiao Ru ; Fingerle-Rowson, Gunter ; Bacher, Michael ; Scher, Larry A. ; Bucala, Richard ; Lan, Hui Y. / Macrophage migration inhibitory factor induces MMP-9 expression : Implications for destabilization of human atherosclerotic plaques. In: Atherosclerosis. 2005 ; Vol. 178, No. 1. pp. 207-215.
@article{e3a9b2e44b684cb29d1f1dea2471fcc3,
title = "Macrophage migration inhibitory factor induces MMP-9 expression: Implications for destabilization of human atherosclerotic plaques",
abstract = "Macrophage migration inhibitory factor (MIF) has been shown to participate in both experimental and human atherogenesis. Expression of MMP-9 has been shown to play a role in the instability of atherosclerotic plaque. Thus, we hypothesize that MIF may participate in the destabilization of atherosclerotic plaques by stimulating MMP-9 expression. This hypothesis was investigated by examining the expression of MIF and MMP-9 in human atherosclerotic plaques using two-color immunostaining and by determining the potential role of MIF in the induction of MMP-9 expression in vascular smooth muscle cells (VSMC) and macrophages in vitro. Two-color immunohistochemistry demonstrated that MIF was strongly upregulated by macrophages and VSMCs. This was associated with marked increase in MMP-9 expression in vulnerable atheromatous plaques, but not in the fibrous lesions. Upregulation of MIF and MMP-9 in vulnerable atheromatous plaques was associated with the weakening of fibrous caps. The role of MIF in MMP-9 expression was demonstrated by the ability of MIF to directly induce MMP-9 mRNA and protein expression in macrophages and in VSMCs in a dose and time-dependent manner, which was blocked by a neutralizing MIF antibody. In conclusion, MIF and MMP-9 are markedly upregulated in vulnerable atheromatous plaques. The ability of MIF to induce MMP-9 expression in VSMCs and macrophages suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.",
keywords = "Atherosclerosis, Macrophages, MIF, MMP-9, Plaque instability, VSMCs",
author = "Kong, {Yao Zhong} and Xiyong Yu and Tang, {Jia Ju} and Xiaosen Ouyang and Huang, {Xiao Ru} and Gunter Fingerle-Rowson and Michael Bacher and Scher, {Larry A.} and Richard Bucala and Lan, {Hui Y.}",
year = "2005",
month = "1",
doi = "10.1016/j.atherosclerosis.2004.08.030",
language = "English (US)",
volume = "178",
pages = "207--215",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Macrophage migration inhibitory factor induces MMP-9 expression

T2 - Implications for destabilization of human atherosclerotic plaques

AU - Kong, Yao Zhong

AU - Yu, Xiyong

AU - Tang, Jia Ju

AU - Ouyang, Xiaosen

AU - Huang, Xiao Ru

AU - Fingerle-Rowson, Gunter

AU - Bacher, Michael

AU - Scher, Larry A.

AU - Bucala, Richard

AU - Lan, Hui Y.

PY - 2005/1

Y1 - 2005/1

N2 - Macrophage migration inhibitory factor (MIF) has been shown to participate in both experimental and human atherogenesis. Expression of MMP-9 has been shown to play a role in the instability of atherosclerotic plaque. Thus, we hypothesize that MIF may participate in the destabilization of atherosclerotic plaques by stimulating MMP-9 expression. This hypothesis was investigated by examining the expression of MIF and MMP-9 in human atherosclerotic plaques using two-color immunostaining and by determining the potential role of MIF in the induction of MMP-9 expression in vascular smooth muscle cells (VSMC) and macrophages in vitro. Two-color immunohistochemistry demonstrated that MIF was strongly upregulated by macrophages and VSMCs. This was associated with marked increase in MMP-9 expression in vulnerable atheromatous plaques, but not in the fibrous lesions. Upregulation of MIF and MMP-9 in vulnerable atheromatous plaques was associated with the weakening of fibrous caps. The role of MIF in MMP-9 expression was demonstrated by the ability of MIF to directly induce MMP-9 mRNA and protein expression in macrophages and in VSMCs in a dose and time-dependent manner, which was blocked by a neutralizing MIF antibody. In conclusion, MIF and MMP-9 are markedly upregulated in vulnerable atheromatous plaques. The ability of MIF to induce MMP-9 expression in VSMCs and macrophages suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.

AB - Macrophage migration inhibitory factor (MIF) has been shown to participate in both experimental and human atherogenesis. Expression of MMP-9 has been shown to play a role in the instability of atherosclerotic plaque. Thus, we hypothesize that MIF may participate in the destabilization of atherosclerotic plaques by stimulating MMP-9 expression. This hypothesis was investigated by examining the expression of MIF and MMP-9 in human atherosclerotic plaques using two-color immunostaining and by determining the potential role of MIF in the induction of MMP-9 expression in vascular smooth muscle cells (VSMC) and macrophages in vitro. Two-color immunohistochemistry demonstrated that MIF was strongly upregulated by macrophages and VSMCs. This was associated with marked increase in MMP-9 expression in vulnerable atheromatous plaques, but not in the fibrous lesions. Upregulation of MIF and MMP-9 in vulnerable atheromatous plaques was associated with the weakening of fibrous caps. The role of MIF in MMP-9 expression was demonstrated by the ability of MIF to directly induce MMP-9 mRNA and protein expression in macrophages and in VSMCs in a dose and time-dependent manner, which was blocked by a neutralizing MIF antibody. In conclusion, MIF and MMP-9 are markedly upregulated in vulnerable atheromatous plaques. The ability of MIF to induce MMP-9 expression in VSMCs and macrophages suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.

KW - Atherosclerosis

KW - Macrophages

KW - MIF

KW - MMP-9

KW - Plaque instability

KW - VSMCs

UR - http://www.scopus.com/inward/record.url?scp=10044226344&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10044226344&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2004.08.030

DO - 10.1016/j.atherosclerosis.2004.08.030

M3 - Article

VL - 178

SP - 207

EP - 215

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 1

ER -