Thrombomodulin overexpression to limit neointima formation.
Thrombomodulin overexpression to limit neointima formation.
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血栓调节蛋白过度表达以限制新内膜形成。
DOI：
10.1161/01.cir.102.3.332
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发表时间：
2000
期刊：
影响因子：
37.8
通讯作者：
Woo,SL
中科院分区：
文献类型：
--
作者：
Waugh,JM;Li-Hawkins,J;Yuksel,E;Kuo,MD;Cifra,PN;Hilfiker,PR;Geske,R;Chawla,M;Thomas,J;Shenaq,SM;Dake,MD;Woo,SL
背景-这些研究的启动，以确认高水平血栓调节蛋白过度表达是足以限制机械过度扩张injurement.Methods和结果后，新生内膜形成表达血栓调节蛋白（Adv/RSV-THM）的腺病毒构建体创建和功能特点，在体外和体内。评价了机械性过度扩张损伤后28天局部血栓调节蛋白过度表达对新生内膜形成的影响。用缓冲液、病毒对照或Adv/RSV-THM处理新西兰白色兔股总动脉，并使其经受机械过度扩张损伤。28天后收获经处理血管（每次处理n=4），并进行评价以确定内膜-中膜（I/M）比。进行了其他实验，以确定细胞外弹性蛋白和胶原蛋白含量的早期（7天）变化;局部巨噬细胞、T细胞和中性粒细胞浸润;以及局部血栓形成，作为观察到的对28天新生内膜形成的影响的潜在贡献因素。在该模型中，该结构显著减少了机械扩张损伤后的新生内膜形成。通过组织学分析，缓冲液对照显示平均I/M比为0.76± 0.06%，而病毒对照达到0.77±0.08%;相比之下，Adv/RSV-THM将I/M比降低至0.47± 0.06%。相对于对照组，Adv/RSV-THM组的局部炎性浸润减少，而基质保持相对保留。早期血栓形成率也降低了Adv/RSV-THM animal.Conclusions-This构建，从而提供了一个可行的技术，促进局部新生内膜抵抗小口径动脉通过减少血栓体积，正常基质保存，并减少局部炎症，而没有炎症损伤，限制了许多其他腺病毒的应用。
Background—These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury.Methods and Results—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 neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76±0.06%, whereas viral controls reached 0.77±0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47±0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals.Conclusions—This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications.
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影响因子：
20.3
作者：
Daniel I. Simon;A. Ezratty;Stephanie A. Francis;Helmut G. Rennke;Joseph Loscalzo
通讯作者：
Daniel I. Simon;A. Ezratty;Stephanie A. Francis;Helmut G. Rennke;Joseph Loscalzo
影响因子：
8.7
作者：
Zempo, N;Koyama, N;Clowes, AW
通讯作者：
Clowes, AW
影响因子：
5.2
作者：
García-Delgado N;Velasco M;Sánchez-Soto C;Díaz-García CM;Hiriart M
通讯作者：
Hiriart M
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
凝血酶受体激活肽可差异性刺激人脐静脉内皮细胞中血小板衍生生长因子的产生、单核细胞粘附和 E-选择素表达。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shankar,R;delaMotte,CA;Poptic,EJ;DiCorleto,PE
通讯作者：
DiCorleto,PE