title: A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease.
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.
authors.affiliation: Nordic Bioscience A/S Herlev Hovedgade 207, DK-2730 Herlev, Denmark ; Department of Clinical Biochemistry and Pharmacology, University Hospital of Southern Denmark Sdr. Boulevard 29 DK-5000 Odense, Denmark.
authors.forename: Natasha
authors.initials: N
authors.lastname: Barascuk
authors.forename: Federica
authors.initials: F
authors.lastname: Genovese
authors.forename: Lise
authors.initials: L
authors.lastname: Larsen
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Zheng
authors.forename: Shu
authors.initials: S
authors.lastname: Sun
authors.forename: Susanne
authors.initials: S
authors.lastname: Hosbond
authors.forename: Tina S
authors.initials: TS
authors.lastname: Poulsen
authors.forename: Axel
authors.initials: A
authors.lastname: Diederichsen
authors.forename: Jesper M
authors.initials: JM
authors.lastname: Jensen
authors.forename: Hans
authors.initials: H
authors.lastname: Mickley
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
keywords: Versican; acute coronary syndrome; atherosclerosis; biomarker; matrix; neo-epitope; remodeling