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

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  • Pathak, Alokkumar
    • Other Affiliation: Carolina Cardiovascular Biology Center
  • Zhao, Renyi
    • Other Affiliation: Carolina Cardiovascular Biology Center
  • Huang, Jianhua
    • Other Affiliation: Carolina Cardiovascular Biology Center
  • Stouffer, George A
    • Affiliation: School of Medicine, Department of Medicine
    • Other Affiliation: Carolina Cardiovascular Biology Center
Abstract
  • Background The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These β3 integrin inhibitors antagonize fibrinogen binding to αIIbβ3 integrins on platelets and ligand binding to αvβ3 integrins on vascular cells. αvβ3 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-β3 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 αIIbβ3 but not αvβ3, 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 αvβ3 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 αvβ3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Alokkumar Pathak et al.; licensee BioMed Central Ltd.
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Journal title
  • Cardiovascular Diabetology
Journal volume
  • 7
Journal issue
  • 1
Page start
  • 36
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1475-2840
Bibliographic citation
  • Cardiovascular Diabetology. 2008 Dec 23;7(1):36
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • August 23, 2012

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