Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice
Aim Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2011-01-01
|
Series: | Biomarker Insights |
Online Access: | https://doi.org/10.4137/BMI.S7777 |
id |
doaj-0e01e220d66f4acf90fcf481d76baa07 |
---|---|
record_format |
Article |
spelling |
doaj-0e01e220d66f4acf90fcf481d76baa072020-11-25T01:23:55ZengSAGE PublishingBiomarker Insights1177-27192011-01-01610.4137/BMI.S7777Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout MiceN. Barascuk0E. Vassiliadis1Q. Zheng2Y. Wang3W. Wang4L. Larsen5L.M. Rasmussen6M.A. Karsdal7Nordic Bioscience A/S, Herlev, Denmark.Nordic Bioscience A/S, Herlev, Denmark.Nordic Bioscience Beijing, Beijing, China.Nordic Bioscience Beijing, Beijing, China.Nordic Bioscience Beijing, Beijing, China.Nordic Bioscience A/S, Herlev, Denmark.Department of Clinical Biochemistry, University Hospital of Southern Denmark, Odense, Denmark.Nordic Bioscience A/S, Herlev, Denmark.Aim Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA) developed to measure a specific MMP12-derived fragment of mimecan, MMCN-151, in apolipoprotein-E knockout (ApoE-KO) mice. Methods and Results A mouse monoclonal antibody raised against MMCN-151 was used to develop a competitive ELISA. The assay was validated using samples from 20 ApoE-KO and 20 wild type [C57 BL/6] male mice fed a normal or high-fat diet (HFD) for up to 20 weeks. The technical reliability of the assay was established with intra-assay variability <2% and inter-assay variability < 10%. The lowest limit of quantification of MMCN-151 was 0.5 ng/ml. ApoE-KO mice fed a HFD for 20 weeks had four-fold increased circulating levels of MMCN-151 compared to baseline, whereas MMCN-151 levels in control mice on HFD increased two-fold compared with baseline. After 10 weeks of a HFD, a significant difference in MMCN-151 levels was observed between ApoE-KO and control mice ( P = 0.005) and became more significant at 20 weeks ( P = 0.002). Conclusions The newly developed assay is a reliable detector of MMCN-151 levels which ultimately may be useful indicators of arterial remodeling in patients affected by atherosclerotic disease.https://doi.org/10.4137/BMI.S7777 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
N. Barascuk E. Vassiliadis Q. Zheng Y. Wang W. Wang L. Larsen L.M. Rasmussen M.A. Karsdal |
spellingShingle |
N. Barascuk E. Vassiliadis Q. Zheng Y. Wang W. Wang L. Larsen L.M. Rasmussen M.A. Karsdal Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice Biomarker Insights |
author_facet |
N. Barascuk E. Vassiliadis Q. Zheng Y. Wang W. Wang L. Larsen L.M. Rasmussen M.A. Karsdal |
author_sort |
N. Barascuk |
title |
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice |
title_short |
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice |
title_full |
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice |
title_fullStr |
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice |
title_full_unstemmed |
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice |
title_sort |
levels of circulating mmcn-151, a degradation product of mimecan, reflect pathological extracellular matrix remodeling in apolipoprotein e knockout mice |
publisher |
SAGE Publishing |
series |
Biomarker Insights |
issn |
1177-2719 |
publishDate |
2011-01-01 |
description |
Aim Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA) developed to measure a specific MMP12-derived fragment of mimecan, MMCN-151, in apolipoprotein-E knockout (ApoE-KO) mice. Methods and Results A mouse monoclonal antibody raised against MMCN-151 was used to develop a competitive ELISA. The assay was validated using samples from 20 ApoE-KO and 20 wild type [C57 BL/6] male mice fed a normal or high-fat diet (HFD) for up to 20 weeks. The technical reliability of the assay was established with intra-assay variability <2% and inter-assay variability < 10%. The lowest limit of quantification of MMCN-151 was 0.5 ng/ml. ApoE-KO mice fed a HFD for 20 weeks had four-fold increased circulating levels of MMCN-151 compared to baseline, whereas MMCN-151 levels in control mice on HFD increased two-fold compared with baseline. After 10 weeks of a HFD, a significant difference in MMCN-151 levels was observed between ApoE-KO and control mice ( P = 0.005) and became more significant at 20 weeks ( P = 0.002). Conclusions The newly developed assay is a reliable detector of MMCN-151 levels which ultimately may be useful indicators of arterial remodeling in patients affected by atherosclerotic disease. |
url |
https://doi.org/10.4137/BMI.S7777 |
work_keys_str_mv |
AT nbarascuk levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT evassiliadis levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT qzheng levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT ywang levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT wwang levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT llarsen levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT lmrasmussen levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice AT makarsdal levelsofcirculatingmmcn151adegradationproductofmimecanreflectpathologicalextracellularmatrixremodelinginapolipoproteineknockoutmice |
_version_ |
1725119966955438080 |