Adenovirus-Mediated Expression of &bgr;-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs
Adenovirus-Mediated Expression of &bgr;-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs
复制标题
腺病毒介导的表达
作者：
Zhengyu Luo;G. Akita;T. Date;Christopher M. Treleaven;K. Vincent;Denise Woodcock;Seng H. Cheng;R. Gregory;Canwen Jiang
背景--血液透析血管通路功能障碍是导致肾脏血液透析患者并发症的最重要原因。动静脉聚四氟乙烯(PTFE)移植物是最常见的血液透析通路，其失败主要是由于静脉吻合口的内膜增生和血栓形成。方法和结果：本研究旨在评价编码肾上腺素能受体激酶羧基末端的腺病毒载体(AD2/&BGR；ARKct)在猪动静脉PTFE移植失败模型中的有效性和安全性。根据临床和病理评估，转导AD2/&BGR；ARKct(每条静脉5E9、5E10或5E11颗粒)没有导致全身毒性。AD2/&BGR；ARKct显著减少移植物/静脉吻合口的新生内膜增生。在组织学和血管造影学测量中，与载体或空病毒载体对照组相比，它还改善了移植物通畅率和血管造影评分。结论：我们的结果表明，将编码&BGR；ARKct的腺病毒载体局部注射到颈静脉是治疗移植血管血液透析血管通路衰竭的一种可行策略。
Background—Hemodialysis vascular access dysfunction is the single most important cause of morbidity in kidney hemodialysis patients. Failure of an arteriovenous polytetrafluoroethylene (PTFE) graft, the most common form of hemodialysis access, is primarily due to intimal hyperplasia and thrombosis at the venous anastomosis. Methods and Results—This study was aimed at evaluating the efficacy and safety of an adenoviral vector (Ad2/&bgr;ARKct) encoding the carboxyl terminus of &bgr;-adrenergic receptor kinase (&bgr;ARKct) in a pig model of arteriovenous PTFE graft failure. Transduction of the external jugular vein with Ad2/&bgr;ARKct (5E9, 5E10, or 5E11 particles per vein) did not result in systemic toxicity, as measured by clinical and pathological assessments. Ad2/&bgr;ARKct significantly reduced neointimal hyperplasia in the graft/vein anastomosis. It also improved the graft patency rate and angiographic score, as measured histologically and angiographically, compared with vehicle or empty viral vector controls. Conclusions—Our results suggest that local administration of adenoviral vectors encoding &bgr;ARKct into the jugular vein represents a viable strategy to treat AV graft hemodialysis vascular access failure.
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G 蛋白信号传导和静脉移植物内膜增生：Gbetagamma 抑制剂减少静脉移植物内膜增生，表明 G 蛋白信号传导在病变发展中发挥着重要作用。
DOI：
10.1161/01.atv.18.8.1275
发表时间：
1998
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Davies,MG;Huynh,TT;Fulton,GJ;Lefkowitz,RJ;Svendsen,E;Hagen,PO;Koch,WJ
通讯作者：
Koch,WJ
血清素、血栓素 A2 和特异性受体拮抗剂对血管平滑肌细胞增殖的影响。
影响因子：
37.8
作者：
Pakala,R;Willerson,JT;Benedict,CR
通讯作者：
Benedict,CR
影响因子：
19.6
作者：
Neyra, NR;Ikizler, TA;Hakim, RM
通讯作者：
Hakim, RM
抑制新内膜血管病变的基因治疗：内皮细胞一氧化氮合酶基因的体内转移。
DOI：
10.1073/pnas.92.4.1137
发表时间：
1995
影响因子：
11.1
作者：
vonderLeyen,HE;Gibbons,GH;Morishita,R;Lewis,NP;Zhang,L;Nakajima,M;Kaneda,Y;Cooke,JP;Dzau,VJ
通讯作者：
Dzau,VJ
影响因子：
37.8
作者：
ASAHARA, T;BAUTERS, C;ISNER, JM
通讯作者：
ISNER, JM