Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker

<p>Abstract</p> <p>Background</p> <p>Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent diffic...

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Main Authors: Vassiliadis Efstathios, Rasmussen Lars M, Byrjalsen Inger, Larsen Dorthe, Chaturvedi Rajiv, Hosbond Susanne, Saabye Lotte, Diederichsen Axel CP, Genovese Federica, Duffin Kevin L, Zheng Qinlong, Chen Xiaoliang, Leeming Diana J, Christiansen Claus, Karsdal Morten A
Format: Article
Language:English
Published: BMC 2012-07-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://www.translational-medicine.com/content/10/1/140
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author Vassiliadis Efstathios
Rasmussen Lars M
Byrjalsen Inger
Larsen Dorthe
Chaturvedi Rajiv
Hosbond Susanne
Saabye Lotte
Diederichsen Axel CP
Genovese Federica
Duffin Kevin L
Zheng Qinlong
Chen Xiaoliang
Leeming Diana J
Christiansen Claus
Karsdal Morten A
author_facet Vassiliadis Efstathios
Rasmussen Lars M
Byrjalsen Inger
Larsen Dorthe
Chaturvedi Rajiv
Hosbond Susanne
Saabye Lotte
Diederichsen Axel CP
Genovese Federica
Duffin Kevin L
Zheng Qinlong
Chen Xiaoliang
Leeming Diana J
Christiansen Claus
Karsdal Morten A
author_sort Vassiliadis Efstathios
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage.</p> <p>Methods</p> <p>A competitive ELISA was developed to specifically measure levels of the titin sequence 12670’ NVTVEARLIK 12679’, derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa).</p> <p>Results</p> <p>Mean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (±43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (±90.14)] (P < 0.05). AMI patients showed 56.3% higher levels [792 ng/ml (±149)] (P < 0.05).</p> <p>Conclusions</p> <p>The titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.</p>
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spelling doaj.art-bd7db3574cdc45f08f6155fed14634902022-12-22T00:29:13ZengBMCJournal of Translational Medicine1479-58762012-07-0110114010.1186/1479-5876-10-140Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarkerVassiliadis EfstathiosRasmussen Lars MByrjalsen IngerLarsen DortheChaturvedi RajivHosbond SusanneSaabye LotteDiederichsen Axel CPGenovese FedericaDuffin Kevin LZheng QinlongChen XiaoliangLeeming Diana JChristiansen ClausKarsdal Morten A<p>Abstract</p> <p>Background</p> <p>Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage.</p> <p>Methods</p> <p>A competitive ELISA was developed to specifically measure levels of the titin sequence 12670’ NVTVEARLIK 12679’, derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa).</p> <p>Results</p> <p>Mean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (±43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (±90.14)] (P < 0.05). AMI patients showed 56.3% higher levels [792 ng/ml (±149)] (P < 0.05).</p> <p>Conclusions</p> <p>The titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.</p>http://www.translational-medicine.com/content/10/1/140TitinCVDMMP-12CardiovascularAcute myocardial infarctionBiomarkerNeoepitope
spellingShingle Vassiliadis Efstathios
Rasmussen Lars M
Byrjalsen Inger
Larsen Dorthe
Chaturvedi Rajiv
Hosbond Susanne
Saabye Lotte
Diederichsen Axel CP
Genovese Federica
Duffin Kevin L
Zheng Qinlong
Chen Xiaoliang
Leeming Diana J
Christiansen Claus
Karsdal Morten A
Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
Journal of Translational Medicine
Titin
CVD
MMP-12
Cardiovascular
Acute myocardial infarction
Biomarker
Neoepitope
title Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
title_full Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
title_fullStr Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
title_full_unstemmed Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
title_short Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
title_sort clinical evaluation of a matrix metalloproteinase 12 cleaved fragment of titin as a cardiovascular serological biomarker
topic Titin
CVD
MMP-12
Cardiovascular
Acute myocardial infarction
Biomarker
Neoepitope
url http://www.translational-medicine.com/content/10/1/140
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