Integrin αvβ3 as a target in the prevention of neointimal hyperplasia
Integrin αvβ3 as a target in the prevention of neointimal hyperplasia
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DOI：
10.1016/j.jvs.2007.02.069
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发表时间：
2007-06-01
影响因子：
4.3
通讯作者：
Choi, Eric T.
中科院分区：
文献类型：
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作者：
Kokubo, Taku;Uchida, Hisashi;Choi, Eric T.
尽管在冠状动脉和外周介入治疗后再狭窄的预防和治疗方面取得了重大进展，但血栓形成和再介入治疗的持续并发症。仍然是该患者群体重复住院的主要因素。多年来，一种名为 α(v)β(3) 整合素的普遍存在的细胞表面受体一直是研究人员预防再狭窄的目标，因为它与细胞外基质的相互作用被认为可以协调平滑肌细胞 (SMC) 从中膜迁移到内膜，这是内膜闭塞性病变形成的重要事件。在发表一致阳性的动物研究表明α(v)β(3)整合素阻断导致新内膜(新内膜)病变形成显着减少后，早期临床试验支持避免靶病变血运重建与使用SMC整合素α(v)β(3)及其相关血小板整合素α(IIb)β(3)拮抗剂之间的联系。然而，随后的一系列临床试验表明，这些拮抗剂不一定通过抑制内膜增生本身来阻止血运重建。随后的其他动物研究表明，事实上，在内膜病变（即动脉粥样硬化斑块、脂肪条纹）中预先存在 SMC 的情况下，通过 β(3) 整合素阻断来抑制 SMC 迁移对于预防内膜增生和再狭窄是无效的方法。然而，鉴于有关 α(v)β(3) 整合素及其拮抗剂的丰富的基础和临床信息，我们在本文中讨论了针对血液透析早期动静脉通路失败的新临床问题，我们讨论了这种旧解决方案的新方法。鉴于动静脉通路的独特性，即在吻合之前动脉和静脉中基本上不存在明显的动脉粥样硬化病变，因此可以再次用β（3）整合素拮抗剂靶向SMC从中膜迁移到新内膜的重要事件。
Although major advances have been made in the prevention and treatment of restenosis following coronary and peripheral interventions, the persistent complications of thrombosis and reintervention. remain a mainstay for repeat hospitalizations in this patient population. For many years, a ubiquitous cell surface receptor called alpha(v)beta(3) integrin was the target of investigators in the prevention of restenosis because its interaction with the extracellular matrix was believed to coordinate the migration of smooth muscle cells (SMCs) from the media to the intima, the seminal event in the formation of intimal occlusive lesion. After the publication of uniformly positive animal studies demonstrating that alpha(v)beta(3) integrin blockade led to a significant reduction in new intimal (neointimal) lesion formation, early clinical trials supported the association of avoidance of target lesion revascularization and the use of antagonists to the SMC integrin alpha(v)beta(3) and its related platelet integrin alpha(IIb)beta(3). However, a series of clinical trials subsequently demonstrated that these antagonists did not necessarily prevent revascularizations by inhibiting intimal hyperplasia per se. Additional animal studies subsequently showed that, indeed, in the setting of pre-existing SMCs in the intimal lesion (ie, atherosclerotic plaque, fatty streaks), inhibiting SMC migration by way of beta(3) integrin blockade was an ineffective approach in the prevention of intimal hyperplasia and restenosis. However, given the wealth of basic and clinical information on the alpha(v)beta(3) integrin and its antagonists, we discuss in this article our new approach to this old solution by targeting a new clinical problem of early failure arteriovenous access for hemodialysis. Given the uniqueness of arteriovenous access in that there are essentially no significant atherosclerotic lesions in the artery and vein prior to the anastomosis, the seminal event of the migration of SMCs from the media to the neointima could by targeted once again with beta(3) integrin antagonists.