1P277 Effects of αvβ3 integrin antagonists on human arterial smooth muscle cell migration to vitronectin

• Published in: Journal of Pharmacological Sciences 2003, Vol.91 (suppl.1), p.157-157
• Main Authors: Takashi Isobe, Atsuhiro Sugidachi, Taketoshi Ogawa, Yumiko Fujisawa, Naoko Suzuki, Yuki Nakanishi, Tamami Shimoji, Masaki Nakanishi, Masaaki Takahashi, Fumitoshi Asai
• Format: Article
• Language: Japanese
• ISSN: 1347-8613

Clinical treatment with abciximab, an anti-β3 integrin antibody, has been associated with a reduction in coronary events, suggesting the pivotal role of β3 integrin on restenosis. The present study was designed to test the hypothesis that αvβ3, antagonists can inhibit the migration of human arterial smooth muscle cells (ASMC). Binding of purified αvβ3 to vitronectin (VN) was completely inhibited by SB265123 (SB), an αvβ3 antagonist, but not by SC-57101A (SC), an αIIbβ3 antagonist. In contrast. SC potently inhibited platelet aggregation, and SB had minimal effects. Adnesion and migration of highly αvβ3-expressed HEK293 cells to VN were inhibited by SB, abciximab and LM609, an anti-αvβ3 antibody, in a concentration-dependent manner. SC and P2, an anti-αIIb β3 antibody, had minimal effects on both adhesion and migration. A further study examining the effects of these antagonists on human ASMC migration to VN showed that only SB inhibited the migration in a concentration-dependent manner. Abciximab, LM609 and SC showed no apparent effects even at the highest concentration. The present studies provide an evidence that there is a discrepancy in efficacy between small synthetic antagonists and antibodies against αvβ3 in preventing ASMC migration.