ED-B fibronectin (ED-B) can be targeted using a novel single chain antibody conjugate and is associated with macrophage accumulation in atherosclerotic lesions
- 134 Downloads
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 wordsatherosclerosis imaging extracellular matrix fibronectin
Unable to display preview. Download preview PDF.
- 2.Botnar RM, Perez AS,Witte S,Wiethoff AJ, Laredo J, Hamilton J, Quist W, Parsons EC Jr, Vaidya A, Kolodziej A, Barrett JA, Graham PB, Weisskoff RM, Manning WJ, Johnstone MT (2004) In vivo molecular imaging of acute and subacute thrombosis using a fibrinbinding magnetic resonance imaging contrast agent. Circulation 109:2023–2029PubMedCrossRefGoogle Scholar
- 3.Bruemmer D, Collins AR, Noh G,Wang W, Territo M, Arias-Magallona S, Fishbein MC, Blaschke F, Kintscher U, Graf K, Law RE, Hsueh WA (2003) Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest 112:1318–1331PubMedCrossRefGoogle Scholar
- 4.Bruemmer D, Riggers U, Holzmeister J, Grill M, Lippek F, Settmacher U,Regitz- Zagrosek V, Fleck E, Graf K (2001) Expression of CD40 in vascular smooth muscle cells and macrophages is associated with early development of human atherosclerotic lesions. Am J Cardiol 87:21–27PubMedCrossRefGoogle Scholar
- 13.Ntziachristos V, Schellenberger EA, Ripoll J,Yessayan D,Graves E,Bogdanov A, Jr., Josephson L,Weissleder R (2004) Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate. Proc Natl Acad Sci U S A 101:12294–12299PubMedCrossRefGoogle Scholar
- 15.Ross R (1999) Atherosclerosis–an inflammatory disease. 340:115–126Google Scholar
- 16.Stawowy P, Kallisch H, Veinot JP, Kilimnik A, Prichett W, Goetze S, Seidah NG, Chretien M, Fleck E, Graf K (2004) Endoproteolytic activation of alpha(v) integrin by proprotein convertase PC5 is required for vascular smooth muscle cell adhesion to vitronectin and integrin- dependent signaling. Circulation 109:770–776PubMedCrossRefGoogle Scholar
- 19.Winter PM, Morawski AM, Caruthers SD,Fuhrhop RW,Zhang H,Williams TA, Allen JS, Lacy EK, Robertson JD, Lanza GM, Wickline SA (2003) Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin- targeted nanoparticles. Circulation 108:2270–2274PubMedCrossRefGoogle Scholar