Authors: Dietrich, T.¹; Perlitz, C.²; Licha, K.²; Stawowy, P.¹; Atrott, K.¹; Tachezy, M.¹; Meyborg, H.¹; Stocker, C.³; Gräfe, M.¹; Fleck, E.¹; Schirner, M.²; Graf, K.⁴

Source: Basic Research in Cardiology, Volume 102, Number 4, July 2007 , pp. 298-307(10)

Publisher: Springer

Abstract:

It has been shown that ED-B fibronectin (ED-B) is a potential target for plaque imaging. The aim of this study was to test a novel modified single chain anti-ED-B antibody (scFv) conjugated for near infrared fluorescence imaging (NIRF) with tetrasulfonated carbocyanine-maleimide (TSC-scFv) and to examine the association of ED-B with the presence of macrophages in a murine model of atherosclerosis. Expression of ED-B was observed in plaque areas in apolipoprotein E-deficient (apoE^-/-) mice which increased with age and plaque load. Robust imaging was possible after explantation of the aorta and demonstrated a strong NIRF signal intensity in focal aortic and brachiocephalic plaque lesions, whereas no signals were found in undiseased areas. Plaque lesion ED-B was expressed by smooth muscle cell and was closely associated to macrophage infiltrates. Although not expressed by the same cell type, there was a significant correlation (p<0.01) between ED-B and macrophage immunoreactivity. In vitro human coronary and mouse smooth muscle cells significantly increased ED-B expression after angiotensin II and TNF-α treatment.This study demonstrates that plaque NIRF imaging is feasible with a novel single chain antibody and that ED-B expression is closely associated with inflammation in experimental atherosclerosis.

Keywords: atherosclerosis; imaging; extracellular matrix; fibronectin

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s00395-007-0652-5

Affiliations: 1: Dept. of Medicine - Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany 2: Research Laboratories Schering AG, Berlin, Germany 3: Helios Klinikum, Charité Campus Buch, Universitätsmedizin Berlin, Berlin, Germany 4: Dept. of Medicine - Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany, Email: graf@dhzb.de

Publication date: 2007-07-01

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