Upregulation of coronary endothelial P-selectin in a monkey heart ischemia reperfusion model

Upregulation of coronary endothelial P-selectin in a monkey heart ischemia reperfusion model
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DOI:
10.1007/s10735-010-9289-z
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发表时间:
2010-10-01
影响因子:
3.2
通讯作者:
Nunn, Adrian D.
Nunn, Adrian D.
中科院分区:
生物学4区
文献类型:
--
作者:
Thomas, Regi;Cheng, Yulan;Nunn, Adrian D.

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用于心肌缺血再灌注(IR)分子成像的靶向超声造影剂的设计需要在与目标发生交叉反应的物种中提供适当的体内模型。 P-选择素 (Psel) 是一种激活依赖性内皮受体,支持流动系统中快速、可逆的细胞粘附。它与 E-选择素和 L-选择素一起构成粘附分子的选择素家族。我们研究了闭胸微创猴心肌 IR 模型中选择素的心肌表达。对麻醉猴进行左前降支(LAD)基于导管的闭塞(30-50 分钟),然后再灌注(3 或 5 小时)。每次手术结束时,动物都会被处死,并切除它们的心脏。使用与恒河猴发生交叉反应的抗人 Psel 抗体(AK-6 克隆)对组织进行免疫组织化学分析。组织病理学特征证实心肌组织中存在IR损伤。 IR 区域血管中 Psel 表达显着增加。然而,在远离 IR 损伤的区域也观察到显着较高的 Psel 免疫反应性。
The design of targeted ultrasound contrast agents for molecular imaging of myocardial ischemia-reperfusion (IR) requires the availablity of an adequate in vivo model in a species in which cross reactivity with the target occurs. P-selectin (Psel) is an activation-dependent endothelial receptor that supports rapid and reversible cell adhesion in a flowing system. Together with E- and L-selectins it constitutes the selectin family of adhesion molecules. We investigated the myocardial expression of selectins in a closed chest minimally invasive monkey myocardial IR model. Catheter-based occlusion (30-50 min) followed by reperfusion (3 or 5 h) of left anterior descending artery (LAD) was performed in anesthetised monkeys. At the end of each procedure animals were killed, and their hearts were excised. The tissues were analyzed immunohistochemically using an anti-human Psel antibody (AK-6 clone) that cross reacts with rhesus monkey. Histopathological features confirm the presence of IR injuries in myocardial tissues. There was significant increase in the Psel expression in vessels from the IR areas. However, significantly higher Psel immunoreactivity was also seen in areas which are distant from IR injuries.