TITLE

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

AUTHOR(S)
Pathak, Alokkumar; Zhao, Renyi; Huang, Jianhua; Stouffer, George A.
PUB. DATE
January 2008
SOURCE
Cardiovascular Diabetology;2008, Vol. 7, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These �3 integrin inhibitors antagonize fibrinogen binding to aIIb�3 integrins on platelets and ligand binding to av�3 integrins on vascular cells. av�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-�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 allb�3 but not av�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 av�3 integrins had no effect on insulin-induced increases in extracellular signalregulated kinase (ERK) activity. Insulin stimulated a rapid increase in the number of vinculincontaining focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulininduced increases in focal adhesions by 100%, 74% and 73%, respectively. Conclusion: These results demonstrate that av�3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.
ACCESSION #
55716396

 

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