Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery:: A randomized, placebo-controlled, double-blinded phase II study
Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery:: A randomized, placebo-controlled, double-blinded phase II study
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DOI：
10.1006/mthe.2002.0638
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发表时间：
2002-07-01
影响因子：
12.4
通讯作者：
Ylä-Herttuala, S
中科院分区：
文献类型：
--
作者：
Mäkinen, K;Manninen, H;Ylä-Herttuala, S
血管内皮生长因子（VEGF）基因治疗可能有助于下肢缺血的治疗。本研究的目的是评价经皮腔内血管成形术（PTA）后局部导管介导的VEGF基因治疗缺血下肢动脉的安全性、血管造影和血流动力学反应。在这项研究中，我们招募了慢性下肢缺血和动脉粥样硬化性腹股沟下闭塞或狭窄的患者，适合PTA。在该研究中，18名患者在血管成形术部位接受2 × 10（10）空斑形成单位（pfu）VEGF-腺病毒（VEGF-Ad），17名患者接受VEGF-质粒/脂质体（VEGF-P/L; 2000 μ g VEGF质粒，2000穆尔DOTMA：DOPE），19名对照患者接受乳酸林格氏液。数字减影血管造影（DSA）用于评估血管分布之前，之后立即和3个月后PTA。评估临床随访资料、基础实验室检查和踝臂指数（ABI）。主要终点为DSA血管分析，次要终点为3个月随访后的再狭窄率、Rutherford分级和ABI。在研究组之间没有检测到主要的基因转移相关副作用或实验室检查差异。然而，抗腺病毒抗体增加61%的VEGF-Ad治疗的患者。对于主要终点，随访DSA显示VEGF治疗组基因转移位点远端（VEGF-Ad P = 0.03，VEGFP/L P = 0.02）和VEGF-Ad组临床最严重缺血区域（P = 0.01）的血管分布增加。至于次要终点，VEGF-Ad和VEGF-P/L组的平均Rutherford分级和ABI显示出统计学显著改善，但在对照组患者中也观察到类似的改善。我们的结论是，导管介导的VEGF基因治疗是安全的，耐受性良好。血管造影显示，VEGF基因转移增加血管后PTA VEGF-Ad-和VEGF-P/L-治疗组。
Vascular endothelial growth factor (VEGF) gene therapy may be useful for the treatment of lower-limb ischemia. The objectives of this study were to evaluate safety and angiographic and hemodynamic responses of local catheter-mediated VEGF gene therapy in ischemic lower-limb arteries after percutaneous transluminal angioplasty (PTA). For this study, we recruited patients with chronic lower-limb ischemia and atherosclerotic infrainguinal occlusion or stenosis suitable for PTA. In the study, 18 patients received 2 X 10(10)plaque-forming units (pfu) VEGF-adenovirus (VEGF-Ad), 17 patients received VEGF-plasmid/liposome (VEGF-P/L; 2000 mug of VEGF plasmid, 2000 mul of DOTMA:DOPE), and 19 control patients received Ringer's lactate at the angioplasty site. Digital subtraction angiography (DSA) was used to evaluate vascularity before, immediately after, and 3 months after the PTA. Clinical follow-up data, basic laboratory tests, and ankle-brachial index (ABI) were evaluated. Primary endpoint was DSA analysis of vascularity, and secondary endpoints were restenosis rate, Rutherford class, and ABI after 3 months follow-up. No major gene transfer-related side effects or differences in laboratory tests were detected between the study groups. However, anti-adenovirus antibodies increased in 61% of the patients treated with VEGF-Ad. For the primary endpoint, follow-up DSA revealed increased vascularity in the VEGF-treated groups distally to the gene transfer site (VEGF-Ad P = 0.03, VEGFP/L P = 0.02) and in the VEGF-Ad group in the region of the clinically most severe ischemia (P = 0.01). As for the secondary endpoints, mean Rutherford class and ABI showed statistically significant improvements in the VEGF-Ad and VEGF-P/L groups, but similar improvements were also seen in the control patients. We conclude that catheter-mediated VEGF gene therapy is safe and well tolerated. Angiography demonstrated that VEGF gene transfer increased vascularity after PTA in both VEGF-Ad- and VEGF-P/L-treated groups.