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Int J Clin Exp Med 2013;6(3):174-184
Original Article
A MMP derived versican neo-epitope is elevated in plasma from patients with
atherosclerotic heart disease
Natasha Barascuk, Federica Genovese, Lise Larsen, Inger Byrjalsen, Qinlong Zheng, Shu Sun, Susanne Hosbond, Tina S Poulsen,
Axel Diederichsen, Jesper M Jensen, Hans Mickley, Thomas C Register, Lars M Rasmussen, Diana J Leeming, Claus Christiansen,
Morten A Karsdal
Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark; Nordic Bioscience Beijing, Life park road 29, Zhongguancun
Life Science Park, Changoing district, 102206 Beijing, China; Department of Clinical Biochemistry and Pharmacology, University
Hospital of Southern Denmark, Sdr. Boulevard 29 DK-5000 Odense, Denmark; Department of Cardiology, University Hospital of
Southern Denmark, Sdr. Boulevard 29 DK-5000 Odense, Denmark; Comparative Medicine Clinical Research Center (TCR, TBC) Wake
Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA; Department of Cardiology, Vejle
Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark
Received February 11, 2013; Accepted March 7, 2013; Epub March 21, 2013; Published March 31, 2013
Abstract: Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix
proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in
macrophage rich areas. The aim of the current study was to develop an immunoassay to detect a specific MMP-12 derived versican
degradation fragment (VCANM) and assess its potential as a biomarker for extracellular matrix remodelling in atherosclerosis. A
mouse monoclonal antibody raised against VCANM was used for the development of a competitive ELISA for detection of the fragment
in plasma. VCANM was measured in plasma of patients with different levels of heart diseases. Patients experiencing I) acute coronary
syndrome, II) stable ischemic heart disease and III) demonstrating high levels of coronary calcium deposits had significantly higher
plasma levels of VCANM compared to a control group of individuals with no detectable coronary calcium deposits. VCANM was also
detected by immunohistochemistry in coronary artery sections of patients with different degrees of atherosclerosis. VCANM ability to
separate patients with atherosclerotic diseases from healthy individuals suggested VCANM as a potential biomarker for the
pathological arterial matrix remodelling associated with atherosclerosis. (IJCEM1302003).
Keywords: Versican, acute coronary syndrome, atherosclerosis, biomarker, matrix, remodeling, neo-epitope
Address correspondence to: Dr. Federica Genovese, Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. Tel:
+45 44 52 52 07; Fax: +45 44 54 88 88; E-mail: fge@nordicbioscience.com
Original Article
A MMP derived versican neo-epitope is elevated in plasma from patients with
atherosclerotic heart disease
Natasha Barascuk, Federica Genovese, Lise Larsen, Inger Byrjalsen, Qinlong Zheng, Shu Sun, Susanne Hosbond, Tina S Poulsen,
Axel Diederichsen, Jesper M Jensen, Hans Mickley, Thomas C Register, Lars M Rasmussen, Diana J Leeming, Claus Christiansen,
Morten A Karsdal
Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark; Nordic Bioscience Beijing, Life park road 29, Zhongguancun
Life Science Park, Changoing district, 102206 Beijing, China; Department of Clinical Biochemistry and Pharmacology, University
Hospital of Southern Denmark, Sdr. Boulevard 29 DK-5000 Odense, Denmark; Department of Cardiology, University Hospital of
Southern Denmark, Sdr. Boulevard 29 DK-5000 Odense, Denmark; Comparative Medicine Clinical Research Center (TCR, TBC) Wake
Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA; Department of Cardiology, Vejle
Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark
Received February 11, 2013; Accepted March 7, 2013; Epub March 21, 2013; Published March 31, 2013
Abstract: Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix
proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in
macrophage rich areas. The aim of the current study was to develop an immunoassay to detect a specific MMP-12 derived versican
degradation fragment (VCANM) and assess its potential as a biomarker for extracellular matrix remodelling in atherosclerosis. A
mouse monoclonal antibody raised against VCANM was used for the development of a competitive ELISA for detection of the fragment
in plasma. VCANM was measured in plasma of patients with different levels of heart diseases. Patients experiencing I) acute coronary
syndrome, II) stable ischemic heart disease and III) demonstrating high levels of coronary calcium deposits had significantly higher
plasma levels of VCANM compared to a control group of individuals with no detectable coronary calcium deposits. VCANM was also
detected by immunohistochemistry in coronary artery sections of patients with different degrees of atherosclerosis. VCANM ability to
separate patients with atherosclerotic diseases from healthy individuals suggested VCANM as a potential biomarker for the
pathological arterial matrix remodelling associated with atherosclerosis. (IJCEM1302003).
Keywords: Versican, acute coronary syndrome, atherosclerosis, biomarker, matrix, remodeling, neo-epitope
Address correspondence to: Dr. Federica Genovese, Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. Tel:
+45 44 52 52 07; Fax: +45 44 54 88 88; E-mail: fge@nordicbioscience.com
