Basic Research in Cardiology

, Volume 102, Issue 4, pp 298–307 | Cite as

ED-B fibronectin (ED-B) can be targeted using a novel single chain antibody conjugate and is associated with macrophage accumulation in atherosclerotic lesions

  • T. Dietrich*
  • C. Perlitz*
  • K. Licha
  • P. Stawowy
  • K. Atrott
  • M. Tachezy
  • H. Meyborg
  • C. Stocker
  • M. Gräfe
  • E. Fleck
  • M. Schirner
  • K. Graf
ORIGINAL CONTRIBUTION

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.

Key words

atherosclerosis imaging extracellular matrix fibronectin 

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Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • T. Dietrich*
    • 1
  • C. Perlitz*
    • 2
  • K. Licha
    • 2
  • P. Stawowy
    • 1
  • K. Atrott
    • 1
  • M. Tachezy
    • 1
  • H. Meyborg
    • 1
  • C. Stocker
    • 3
  • M. Gräfe
    • 1
  • E. Fleck
    • 1
  • M. Schirner
    • 2
  • K. Graf
    • 1
  1. 1.Dept. of Medicine – CardiologyDeutsches Herzzentrum BerlinBerlinGermany
  2. 2.Research Laboratories Schering AGBerlinGermany
  3. 3.Helios Klinikum, Charité Campus BuchUniversitätsmedizin BerlinBerlinGermany

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