title: ED-B fibronectin (ED-B) can be targeted using a novel single chain antibody conjugate and is associated with macrophage accumulation in atherosclerotic lesions.
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-alpha 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.
authors.affiliation: Dept. of Medicine - Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Thore
authors.initials: T
authors.lastname: Dietrich
authors.forename: Christin
authors.initials: C
authors.lastname: Perlitz
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Philipp
authors.initials: P
authors.lastname: Stawowy
authors.forename: Kirstin
authors.initials: K
authors.lastname: Atrott
authors.forename: Michael
authors.initials: M
authors.lastname: Tachezy
authors.forename: Heike
authors.initials: H
authors.lastname: Meyborg
authors.forename: Carolin
authors.initials: C
authors.lastname: Stocker
authors.forename: Michael
authors.initials: M
authors.lastname: Gräfe
authors.forename: Eckart
authors.initials: E
authors.lastname: Fleck
authors.forename: Michael
authors.initials: M
authors.lastname: Schirner
authors.forename: Kristof
authors.initials: K
authors.lastname: Graf
mesh_terms: D000818:Animals; D000906:Antibodies; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002232:Carbocyanines; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes; D006801:Humans; D007135:Immunoglobulin Variable Region; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism
chemical_list: D000906:Antibodies; D001057:Apolipoproteins E; D002232:Carbocyanines; D002791:Cholesterol, Dietary; C067625:FN1 protein, human; D005353:Fibronectins; D005456:Fluorescent Dyes; D007135:Immunoglobulin Variable Region