Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model

Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model
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DOI:
10.1016/j.cardiores.2005.08.013
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发表时间:
2006-01-01
影响因子:
10.8
通讯作者:
Sawamura, T
Sawamura, T
中科院分区:
医学1区
文献类型:
--
作者:
Hinagata, J;Kakutani, M;Sawamura, T

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目的:LOX-1是一种多配体受体,最初被鉴定为内皮氧化型低密度脂蛋白受体。LOX-1表达也在平滑肌细胞中响应于促炎和氧化刺激而被诱导。在这里,我们报告的LOX-1在内膜增生,其中促炎和氧化刺激increased.Methods和结果的作用:左颈总动脉的大鼠损伤的球囊导管。LOX-1的表达在球囊损伤后24 h内显著增加,并在第7天达到高峰。LOX-1的表达主要在中膜平滑肌细胞中观察到,直到第3天,然后转移到内膜平滑肌细胞为主。在第14天,表达集中在再生的内皮细胞中。为了检查LOX-1在内膜平滑肌细胞生长中的贡献作用,在球囊损伤后每3天静脉内给予大鼠抗LOX 1抗体。与对照IgG相比,抗LOX-1抗体给药有效抑制内膜增生、氧化应激和白细胞浸润。这些结果表明,LOX-1的表达的重要性,在新生内膜形成的发病机制,结合氧化应激和白细胞infiltration.Conclusion:LOX-1表达的平滑肌细胞参与内膜增生在大鼠模型的球囊损伤。LOX-1活性调控是预防血管成形术后再狭窄的一个新的潜在治疗靶点。(c)2005年欧洲心脏病学会。Elsevier B. V.出版,保留所有权利。
Objective: LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor. LOX-1 expression is also induced in smooth muscle cells in response to proinflammatory and oxidative stimuli. Here, we report on the role of LOX-1 in intimal hyperplasia, in which proinflammatory and oxidative stimuli are increased.Methods and results: Left common carotid artery of rat was injured by a balloon catheter. The expression of LOX-1 was significantly increased within 24 h after the balloon injury and peaked at day 7. LOX-1 expression was observed predominantly in medial smooth muscle cells until day 3, and then shifted to predominantly intimal smooth muscle cells. At day 14, the expression was concentrated in the regenerated endothelial cells. To examine the contributory role of LOX-1 in the growth of intimal smooth muscle cells, rats were administered anti-LOX1 antibody intravenously every 3 days after balloon injury. Anti-LOX-1 antibody administration effectively suppressed intimal hyperplasia, oxidative stress, and leukocyte infiltration compared with control IgG. These findings suggest the importance of LOX-1 expression in the pathogenesis of neointimal formation in conjunction with oxidative stress and leukocyte infiltration.Conclusion: The LOX-1 expressed in smooth muscle cells is involved in intimal hyperplasia in a rat model of balloon injury. Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.