Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells.
Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells.
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DOI：
10.1186/1475-2840-7-36
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发表时间：
2008-12-23
影响因子：
9.3
通讯作者：
Stouffer, George A.
中科院分区：
文献类型：
--
作者：
Pathak, Alokkumar;Zhao, Renyi;Huang, Jianhua;Stouffer, George A.
阿昔单抗（c7 E3 Fab）或依替巴肽的使用改善了接受经皮冠状动脉介入治疗的糖尿病患者的临床结局。这些β3整联蛋白抑制剂可拮抗纤维蛋白原与血小板上αIIbβ3整联蛋白的结合以及配体与血管细胞上αvβ3整联蛋白的结合。αvβ3整联蛋白影响各种细胞类型对胰岛素的反应，但对人主动脉平滑肌细胞（HASMC）的影响尚不清楚。胰岛素引起HASMC剂量依赖性增殖反应。用m7 E3（阿昔单抗衍生自的抗β3整联蛋白单克隆抗体）、c7 E3或LM 609预处理分别抑制对胰岛素的增殖反应81%、59%和28%。依替巴肽或环RGD肽完全消除胰岛素诱导的增殖，而与αIIbβ3结合但不与αvβ3结合的替罗非班则无作用。胰岛素诱导的c-Jun NH 2-末端激酶-1（JNK 1）活性增加可被m7 E3和eptifibatide部分抑制，而αvβ3整合素的拮抗作用对胰岛素诱导的细胞外信号调节激酶（ERK）活性增加无影响。胰岛素刺激了每个细胞中含有黏着斑蛋白的粘着斑数量的快速增加，并且用m7 E3、c7 E3或依替巴肽治疗分别抑制了胰岛素诱导的粘着斑增加100%、74%和73%。这些结果表明αvβ3拮抗剂抑制胰岛素处理的HASMC的信号传导、粘着斑形成和增殖。
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. 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. These results demonstrate that αvβ3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.
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DOI：
10.1016/s0735-1097(99)00650-6
发表时间：
2000-03-15
影响因子：
24
作者：
Bhatt, DL;Marso, SP;Topol, EJ
通讯作者：
Topol, EJ
DOI：
10.1083/jcb.130.2.441
发表时间：
1995-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Filardo EJ;Brooks PC;Deming SL;Damsky C;Cheresh DA
通讯作者：
Cheresh DA
DOI：
10.1073/pnas.84.18.6471
发表时间：
1987-09-01
影响因子：
11.1
作者：
CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
37.8
作者：
Lele, M;Sajid, M;Stouffer, GA
通讯作者：
Stouffer, GA
影响因子：
5.5
作者：
Sajid, M;Zhao, R;Stouffer, GA
通讯作者：
Stouffer, GA