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: Thore Dietrich, Christin Perlitz, Kai Licha, Philipp Stawowy, Kirstin Atrott, Michael Tachezy, Heike Meyborg, Carolin Stocker, Michael Gräfe, Eckart Fleck, Michael Schirner, Kristof Graf
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 102 Issue 4 Pg. 298-307 (Jul 2007) ISSN: 0300-8428 [Print] Germany
• PMID: 17468934 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Apolipoproteins E
• Carbocyanines
• Cholesterol, Dietary
• FN1 protein, human
• Fibronectins
• Fluorescent Dyes
• Immunoglobulin Variable Region

Topics

• Animals
• Antibodies
• Aorta, Thoracic (metabolism, pathology)
• Apolipoproteins E (deficiency, genetics, metabolism)
• Atherosclerosis (chemically induced, genetics, metabolism, pathology)
• Carbocyanines
• Cells, Cultured
• Cholesterol, Dietary (administration & dosage)
• Coronary Artery Disease (metabolism, pathology)
• Disease Models, Animal
• Feasibility Studies
• Fibronectins (immunology, metabolism)
• Fluorescent Antibody Technique, Direct
• Fluorescent Dyes
• Humans
• Immunoglobulin Variable Region
• Macrophages (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle, Smooth, Vascular (metabolism)