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. 2013;6(3):174-84.
Epub 2013 Mar 21.

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Natasha Barascuk  1 , 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
Affiliations

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Natasha Barascuk et al. Int J Clin Exp Med. 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.

Keywords: Versican; acute coronary syndrome; atherosclerosis; biomarker; matrix; neo-epitope; remodeling.

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Figures

Figure 1
Figure 1
Test of antibody specificity towards VCANM neo-epitope. Samples added and tested in a competitive ELISA setting were: elongated peptide, uncleaved versican (VCAN), MMP-8 cleaved versican (VCAN+MMP-8), MMP-12 cleaved versican (VCAN+MMP-12) and Cathepsin K cleaved versican (VCAN+CatK).
Figure 2
Figure 2
Immunohistochemical analysis of VCANM on LAD coronary arteries from patients with different degrees of atherosclerosis. The photomicrographs show a particular of the plaque region (original magnification, x40) with presence of VCANM localized at the plaque edges (arrows).
Figure 3
Figure 3
Plasma levels of VCANM measured in patients diagnosed with acute coronary syndrome (ACS), high deposits of coronary calcium (CT-plus Ca), stable ischemic heart disease (IHD) and compared with age-matched controls comprising individuals with no detectable coronary calcium deposits (CT-no Ca). Individual values are shown and the group mean and SEM are indicated as line and error bars. * = p<0.05; *** = p<0.0005.
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