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DOI: 10.1055/s-0037-1615765
7E3 F(ab’)2, an Effective Antagonist of Rat αIIbβ3 and αvβ3, Blocks In Vivo Thrombus Formation and In Vitro Angiogenesis
Publication History
Received
17 August 2000
Accepted after resubmission
28 December 2000
Publication Date:
11 December 2017 (online)
Summary
Abciximab (c7E3 Fab, ReoPro®) blocks GPIIb/IIIa and αvβ3 and inhibits thrombotic and proliferative events only in humans and non-human primates. The bivalent F(ab’)2 fragment is an effective anti-thrombotic agent in canine models. In the present study, 7E3 F(ab’)2 was also found to bind to rat GPIIb/IIIa (KD = 27 ± 4 g/mL) and αvβ3 (KD = 9 ± 8 μg/mL), to block in vitro rat platelet aggregation (IC50 = 16 ± 6 μg/mL), and to inhibit αvβ3-mediated microvessel sprout formation in a rat aortic ring assay. Following administration of 7E3 F(ab’)2 (4 mg/kg) to rats, platelet aggregation was completely blocked for up to 6 h and thrombus formation in response to a rat abdominal aorta double crush injury was prevented. Effective chronic dosing was achieved with 6 mg/kg daily I.P. injections. In vitro mixing experiments indicated that 7E3 F(ab’)2 redistributed to unlabeled platelets in 2 h. Ex vivo, 7E3 F(ab’)2 was detected on platelets for up to 4 days after a single 4-mg/kg injection. These data suggest that 7E3 F(ab’)2 may be a useful agent to study the effects of GPIIb/IIIa and αvβ3 blockade in rat models of thrombosis and vascular disease.