Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model.
Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model.
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血栓调节蛋白的局部过度表达可在兔模型中体内预防动脉血栓形成。
DOI：
10.1161/01.res.84.1.84
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发表时间：
1999
影响因子：
20.1
通讯作者：
Woo,SL
中科院分区：
文献类型：
--
作者：
Waugh,JM;Yuksel,E;Li,J;Kuo,MD;Kattash,M;Saxena,R;Geske,R;Thung,SN;Shenaq,SM;Woo,SL
内皮凝血调节素通过结合凝血酶并随后将蛋白C转化为活性形式（一种强效抗凝剂），在止血中起关键作用。因此，血栓调节素代表了维持正常血管通畅的中心机制。然而，血栓调节蛋白在受干扰的内皮细胞中表达降低，易导致血栓闭塞。建立了表达血栓调节素的腺病毒构建体（Adv/RSV-THM），并在体外和体内进行了功能表征。随后，在动脉血栓形成的停滞/损伤模型中，研究了局部过表达血栓调节蛋白对体内血栓形成的影响。该结构在所有动物中都能防止动脉血栓形成，而病毒和非病毒对照组通常会形成闭塞性血栓。通过组织学分析，非病毒对照组的血管内血栓闭塞率平均为70.52±3.72%，而病毒对照组的血栓闭塞率为86.85±2.82%；相比之下，Adv/RSV-THM在横截面上可使腔内血栓形成减少28.61±3.31%。与对照组相比，血栓调节素组没有观察到明显的内膜-中膜比率。与对照组相比，Adv/RSV-THM组的局部粒细胞和巨噬细胞浸润明显减少，而与非病毒对照组相比，病毒对照组的中性粒细胞浸润增加。因此，这种结构为促进局部血栓抵抗性小口径动脉提供了一种可行的技术，而没有限制许多其他腺病毒应用的炎症损伤。
—Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form, a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi. By histological analysis, nonviral controls exhibited intravascular thrombus occluding a mean of 70.52±3.72% of available lumen, while viral controls reached 86.85±2.82% thrombotic occlusion; in contrast, Adv/RSV-THM reduced thrombosis to 28.61±3.31% of lumen in cross section. No significant intima-to-media ratio was observed in the thrombomodulin group relative to controls. Local infiltration of granulocytes and macrophages significantly decreased in the Adv/RSV-THM group relative to controls, while neutrophilic infiltration increased in viral controls relative to nonviral controls. This construct thus offers a viable technique for promoting a locally thromboresistant small-caliber artery, without the inflammatory damage that has limited many other adenoviral applications.
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影响因子：
56.9
作者：
E. Nabel;G. Plautz;G. Nabel
通讯作者：
E. Nabel;G. Plautz;G. Nabel
使用直接应用于水凝胶涂层血管成形术球囊的纯 DNA 进行动脉基因转移。
影响因子：
4.2
作者：
Riessen,R;Rahimizadeh,H;Blessing,E;Takeshita,S;Barry,JJ;Isner,JM
通讯作者：
Isner,JM
单克隆抗体 7E3 Fab 在溶栓治疗后可显着抑制血小板聚集。
影响因子：
24
作者：
Neal S. Kleiman;E. Ohman;Califf Rm;Barry S. George;D. Kereiakes;F. Aguirre;H. Weisman;Thomas Schaible;E. J. Topol
通讯作者：
E. J. Topol
影响因子：
20.1
作者：
LEE, SW;TRAPNELL, BC;DICHEK, DA
通讯作者：
DICHEK, DA
凝血酶诱导的内皮细胞功能障碍。
影响因子：
6.7
作者：
M. Rabiet;J. Plantier;E. Dejana
通讯作者：
E. Dejana