Eptifibatide and 7E3, but not tirofiban, inhibit αvβ3 integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin
Eptifibatide and 7E3, but not tirofiban, inhibit αvβ3 integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin
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DOI：
10.1161/hc3101.092199
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发表时间：
2001-07-31
期刊：
影响因子：
37.8
通讯作者：
Stouffer, GA
中科院分区：
文献类型：
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作者：
Lele, M;Sajid, M;Stouffer, GA
背景-我们的目的是确定阿昔单抗、埃替非巴肽或替罗非班是否抑制配体与人主动脉平滑肌细胞 (HASMC) 或人脐静脉内皮细胞 (HUVEC) 上的 α (v)β (3) 整合素结合。阿昔单抗以相似的亲和力结合血小板上的 α (III)、β (3) 和 HUVEC 上的 α (v)β (3)，而依替巴肽和替罗非班被认为对 α (IIb)β (3) 具有高度特异性。然而，依替巴肽不结合血管 α (v)β (3) 整合素的结论可能还为时过早，因为最近的研究表明 α (v)β (3) 对各种配体（包括拮抗剂）的亲和力会受到调节。 方法和结果-Abciximab 和 7E3（抗 β (3) 整合素单克隆抗体） 阿昔单抗衍生而来，以特异性和可饱和的方式结合HASMC上的α(v)β(3)，其亲和力类似于与血小板上的α(IIb)β(3)的结合。 7E3和依替巴肽抑制α(v)β(3)介导的HASMC与血小板反应蛋白(TSP)和凝血酶原的附着，但对α(v)β(5)或β(1)介导的HASMC与玻连蛋白、胶原或纤连蛋白包被或非包被的组织培养板的附着没有影响。依替巴肽的抑制作用在强度上与7E3相似并且不相加。 Eptifibatide 和 7E3 抑制 alpha (v)beta (3) 介导的 HUVEC 附着。替罗非班对 HASMC 与细胞外基质蛋白的附着仅具有非特异性作用。在细胞增殖测定中，依替巴肽抑制HASMC和表达β(3)整合素的HEK细胞对α(v)β(3)介导的可溶性TSP反应。结论-依替巴肽和7E3，但不是替罗非班，特异性抑制α(v)β(3)介导的人平滑肌和内皮细胞的结合。
Background-Our objective was to determine whether abciximab, eptifibatide, or tirofiban inhibited ligand binding to alpha (v)beta (3) integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds alpha (III),beta (3) on platelets and alpha (v)beta (3) on HUVECs with similar affinity, whereas eptifibatide and tirofiban are thought to be highly Specific for alpha (IIb)beta (3). The conclusion that eptifibatide does not bind vascular alpha (v)beta (3) integrins may be premature, however, because recent studies have demonstrated that the affinity of alpha (v)beta (3) for various ligands, including antagonists, is subject to modulation.Methods and Results-Abciximab and 7E3, the anti-beta (3) integrin monoclonal antibody from which abciximab was derived, bound alpha (v)beta (3) on HASMCs in a specific and saturable manner and with an affinity similar to binding to alpha (IIb)beta (3) on platelets. 7E3 and eptifibatide inhibited alpha (v)beta (3)-mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on alpha (v)beta (5)- or beta (1)-mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of eptifibatide was similar in magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited alpha (v)beta (3)-mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, eptifibatide inhibited alpha (v)beta (3)-mediated responses to soluble TSP by HASMCs and beta (3) integrin-expressing HEK cells.Conclusions-Eptifibatide and 7E3, but not tirofiban, specifically inhibit alpha (v)beta (3)-mediated binding of human smooth muscle and endothelial cells.