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Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

Creators: Pathak, Alokkumar, Zhao, Renyi, Huang, Jianhua, Stouffer, George A

  • File Type: pdf | Filesize: 698.8 KB
  • Date Added: 2012-08-23
  • Date Created: 2008-12-23

Abstract Background The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These &#946;3 integrin inhibitors antagonize fibrinogen binding to &#945;IIb&#946;3 integrins on platelets and ligand binding to &#945;v&#946;3 integrins on vascular cells. &#945;v&#946;3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC) are unknown. Results and discussion Insulin elicited a dose-dependent proliferative response in HASMC. Pretreatment with m7E3 (an anti-&#946;3 integrin monoclonal antibody from which abciximab is derived), c7E3 or LM609 inhibited proliferative responses to insulin by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely abolished insulin-induced proliferation whereas tirofiban, which binds &#945;IIb&#946;3 but not &#945;v&#946;3, had no effect. Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1) activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of &#945;v&#946;3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK) activity. Insulin stimulated a rapid increase in the number of vinculin-containing focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively. Conclusion These results demonstrate that &#945;v&#946;3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.