Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart
Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart
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DOI：
10.1016/s0022-5223(98)70455-6
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发表时间：
1998-01-01
影响因子：
6
通讯作者：
Rosengart, TK
中科院分区：
文献类型：
--
作者：
Mack, CA;Patel, SR;Rosengart, TK
目的：血管内皮生长因子（VEGF）是一种有效的血管生成介质，可以通过复制缺陷型腺病毒（Ad）载体递送至靶组织。我们假设将表达 VEGF(121) 互补脱氧核糖核酸 (Ad(GV)VEGF121.10) 的 Ad 载体直接施用到缺血心肌区域将增强侧支血管形成并改善区域灌注和功能，方法：对约克夏猪进行开胸手术并在回旋冠状动脉上放置 Ameroid 缩窄器（Research Instruments & MFG，Corvallis，Ore.），三周随后，通过使用 Tc-99m 标记的 sestamibi 的单光子发射计算机断层扫描成像 (SPECT) 以及休息和应激期间的超声心动图评估心肌灌注和功能，将 Ad(GV)VEGF121.10 (n = 7) 或对照载体 AdNull (n = 8) 直接注入心肌回旋分布的 10 个位点（10(8) pfu/位点）。四个星期后，重复这些研究并进行离体血管造影。结果：载体施用后 4 周的 SPECT 成像显示，与 AdNull 对照动物相比，Ad(GV)VEFG121.10 处理的动物应激时缺血区域显着减少 (p = 0.005)，同时负荷超声心动图显示与 AdNull 对照动物相比，Ad(GV)VEGF121.10 动物的节段性壁增厚有所改善 (p = 0.03)， Ad(GV)VEGF121.10 动物的回旋分布功能几乎正常化，通过血管造影评估的 Ad(GV)VEGF121.10 动物中的侧支血管发育也显着大于 AdNull 对照动物 (p = 0.04)，Ad(GV)VEGF121.10 动物中的回旋充盈几乎完全重建，结论：表达 VEGF(121) cDNA 的 Ad 载体可诱导这种策略可能对不可能进行完全血运重建的缺血性心脏病患者有用。
Objectives: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF(121) complementary deoxyribonucleic acid (Ad(GV)VEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function, Methods: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery, Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with Tc-99m-labeled sestamibi and by echocardiography during rest and stress, Ad(GV)VEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. Results: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in Ad(GV)VEFG121.10-treated animals compared with AdNull control animals (p = 0.005), Stress echocardiography at the same time demonstrated improved segmental wall thickening in Ad(GV)VEGF121.10 animals compared with AdNull control animals (p = 0.03), with Ad(GV)VEGF121.10 animals showing nearly normalized function in the circumflex distribution, Collateral vessel development assessed by angiography was also significantly greater in Ad(GV)VEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in Ad(GV)VEGF121.10 animals, Conclusions: An Ad vector expressing the VEGF(121) cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function, Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.