Thromboresistance of balloon-injured porcine carotid arteries after local gene transfer of human tissue factor pathway inhibitor.
Thromboresistance of balloon-injured porcine carotid arteries after local gene transfer of human tissue factor pathway inhibitor.
复制标题
人组织因子途径抑制剂局部基因转移后球囊损伤的猪颈动脉的血栓抵抗。
DOI：
10.1161/01.cir.101.3.289
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发表时间：
2000
期刊：
影响因子：
37.8
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Zoldhelyi,P;McNatt,J;Shelat,HS;Yamamoto,Y;Chen,ZQ;Willerson,JT
背景——组织因子途径抑制剂 (TFPI) 是因子 Xa 和凝血起始复合物组织因子/因子 VIIa 的内源性抑制剂。方法和结果——为了研究 TFPI 基因转移对血栓形成的影响，用编码人 TFPI (Ad-TFPI) 的腺病毒 (Ad-TFPI) 或对照病毒对球囊损伤的猪颈动脉进行局部治疗。通过在体内转导后培养的猪颈动脉条件培养基中检测人TFPI来证实TFPI的基因转移。术后 5 天用多普勒探头测量颈动脉血流时，8 只对照猪中有 7 只在受伤颈动脉收缩 40% 后出现循环血流变化 (CFV)，所有对照处理的动脉在 70% 收缩后闭塞。相比之下，在 40% 收缩后，8 头 Ad-TFPI 处理的猪中只有 1 只观察到 CFV，在 70% 收缩后 8 头中只有 3 头闭塞（分别为 P=0.0027 和 P=0.007）。在增量肾上腺素输注过程中，70% 收缩后开放的 5 条 TFPI 转导动脉均未出现 CFV。结论 — 与基线相比，全身止血变量和血小板聚集未受损，表明 TFPI 基因转导可以在存在严重剪切应力且未检测到止血损伤的情况下预防动脉血栓形成。
Background—Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of factor Xa and the coagulant initiator complex tissue factor/factor VIIa.Methods and Results—To study the effects of TFPI gene transfer on thrombus formation, balloon-injured porcine carotid arteries were treated locally with an adenovirus encoding human TFPI (Ad-TFPI) or control virus. Gene transfer of TFPI was confirmed by detection of human TFPI in the conditioned medium of porcine carotid arteries kept in culture after in vivo transduction. When carotid flow was measured with Doppler probe 5 days after surgery, cyclic flow variations (CFVs) developed in 7 of 8 control pigs after constriction of the injured carotid artery by 40%, and all control-treated arteries occluded after 70% constriction. In contrast, CFVs were observed in only 1 of 8 Ad-TFPI–treated pigs after 40% constriction, and only 3 of 8 occluded after constriction by 70% (P=0.0027 andP=0.007, respectively). None of the 5 TFPI-transduced arteries open after 70% constriction developed CFVs during an incremental epinephrine infusion.Conclusions—Compared with baseline, systemic hemostatic variables and platelet aggregation were unimpaired, suggesting that TFPI gene transfer can prevent arterial thrombosis in the presence of severe shear stress and without detectable hemostatic impairment.