Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

Nynke A. Jager; Bastiaan M. Wallis de Vries; Jan-Luuk Hillebrands; Niels J. Harlaar; Rene A. Tio; Riemer H. J. A. Slart; Gooitzen M. van Dam; Hendrikus H. Boersma; Clark J. Zeebregts; Johanna Westra

doi:10.1007/s11307-015-0882-0

Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

Nynke A. Jager, Bastiaan M. Wallis de Vries, Jan-Luuk Hillebrands, Niels J. Harlaar, Rene A. Tio, Riemer H. J. A. Slart, Gooitzen M. van Dam, Hendrikus H. Boersma, Clark J. Zeebregts^*, Johanna Westra

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.

Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense (TM) 680 and imaged with IVISA (R) Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.

There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and alpha SMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.

MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.

Original language	English
Pages (from-to)	283-291
Number of pages	9
Journal	Molecular Imaging and Biology
Volume	18
Issue number	2
DOIs	https://doi.org/10.1007/s11307-015-0882-0
Publication status	Published - Apr-2016

Keywords

Matrix metalloproteinase
Macrophage
Atherosclerotic
plaque
Smooth muscle cell
MMPSense
INFLAMMATION
DISEASE
VULNERABILITY
INSTABILITY
POLARIZATION
EXPRESSION
INHIBITORS
STABILITY
STENOSIS
RUPTURE

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Jager, N. A., de Vries, B. M. W., Hillebrands, J.-L., Harlaar, N. J., Tio, R. A., Slart, R. H. J. A., van Dam, G. M., Boersma, H. H., Zeebregts, C. J., & Westra, J. (2016). Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets. Molecular Imaging and Biology, 18(2), 283-291. https://doi.org/10.1007/s11307-015-0882-0

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title = "Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets",

abstract = "In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense (TM) 680 and imaged with IVISA (R) Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and alpha SMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.",

keywords = "Matrix metalloproteinase, Macrophage, Atherosclerotic, plaque, Smooth muscle cell, MMPSense, INFLAMMATION, DISEASE, VULNERABILITY, INSTABILITY, POLARIZATION, EXPRESSION, INHIBITORS, STABILITY, STENOSIS, RUPTURE",

author = "Jager, {Nynke A.} and {de Vries}, {Bastiaan M. Wallis} and Jan-Luuk Hillebrands and Harlaar, {Niels J.} and Tio, {Rene A.} and Slart, {Riemer H. J. A.} and {van Dam}, {Gooitzen M.} and Boersma, {Hendrikus H.} and Zeebregts, {Clark J.} and Johanna Westra",

year = "2016",

month = apr,

doi = "10.1007/s11307-015-0882-0",

language = "English",

volume = "18",

pages = "283--291",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer",

number = "2",

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Jager, NA, de Vries, BMW, Hillebrands, J-L, Harlaar, NJ, Tio, RA, Slart, RHJA , van Dam, GM , Boersma, HH , Zeebregts, CJ & Westra, J 2016, 'Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets', Molecular Imaging and Biology, vol. 18, no. 2, pp. 283-291. https://doi.org/10.1007/s11307-015-0882-0

Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets. / Jager, Nynke A.; de Vries, Bastiaan M. Wallis; Hillebrands, Jan-Luuk et al.
In: Molecular Imaging and Biology, Vol. 18, No. 2, 04.2016, p. 283-291.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

AU - Jager, Nynke A.

AU - de Vries, Bastiaan M. Wallis

AU - Hillebrands, Jan-Luuk

AU - Harlaar, Niels J.

AU - Tio, Rene A.

AU - Slart, Riemer H. J. A.

AU - van Dam, Gooitzen M.

AU - Boersma, Hendrikus H.

AU - Zeebregts, Clark J.

AU - Westra, Johanna

PY - 2016/4

Y1 - 2016/4

N2 - In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense (TM) 680 and imaged with IVISA (R) Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and alpha SMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.

AB - In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense (TM) 680 and imaged with IVISA (R) Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and alpha SMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.

KW - Matrix metalloproteinase

KW - Macrophage

KW - Atherosclerotic

KW - plaque

KW - Smooth muscle cell

KW - MMPSense

KW - INFLAMMATION

KW - DISEASE

KW - VULNERABILITY

KW - INSTABILITY

KW - POLARIZATION

KW - EXPRESSION

KW - INHIBITORS

KW - STABILITY

KW - STENOSIS

KW - RUPTURE

U2 - 10.1007/s11307-015-0882-0

DO - 10.1007/s11307-015-0882-0

M3 - Article

C2 - 26377769

SN - 1536-1632

VL - 18

SP - 283

EP - 291

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 2

ER -

Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

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Keywords

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