Mäkinen Kimmo, Manninen Hannu, Hedman Marja, Matsi Pekka, Mussalo Hanna, Alhava Esko, Ylä-Herttuala Seppo
Department of Surgery, University of Kuopio, Kuopio, Finland.
Mol Ther. 2002 Jul;6(1):127-33. doi: 10.1006/mthe.2002.0638.
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 2x10(10) plaque-forming units (pfu) VEGF-adenovirus (VEGF-Ad), 17 patients received VEGF-plasmid/liposome (VEGF-P/L; 2000 microg of VEGF plasmid, 2000 microl 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.
血管内皮生长因子（VEGF）基因疗法可能对治疗下肢缺血有用。本研究的目的是评估经皮腔内血管成形术（PTA）后，局部导管介导的VEGF基因疗法在缺血性下肢动脉中的安全性、血管造影和血流动力学反应。在本研究中，我们招募了患有慢性下肢缺血且适合PTA的动脉粥样硬化性腹股沟下闭塞或狭窄患者。在研究中，18例患者接受2×10¹⁰空斑形成单位（pfu）的VEGF腺病毒（VEGF-Ad），17例患者接受VEGF质粒/脂质体（VEGF-P/L；2000微克VEGF质粒，2000微升DOTMA:DOPE），19例对照患者在血管成形术部位接受乳酸林格液。数字减影血管造影（DSA）用于评估PTA前、后即刻和3个月后的血管情况。评估临床随访数据、基础实验室检查和踝肱指数（ABI）。主要终点是血管造影的血管情况分析，次要终点是3个月随访后的再狭窄率、卢瑟福分级和ABI。研究组之间未检测到与基因转移相关的主要副作用或实验室检查差异。然而，61%接受VEGF-Ad治疗的患者抗腺病毒抗体增加。对于主要终点，随访DSA显示，VEGF治疗组在基因转移部位远端的血管增多（VEGF-Ad P=0.03，VEGF-P/L P=0.02），且VEGF-Ad组在临床缺血最严重区域血管增多（P=0.01）。至于次要终点，VEGF-Ad组和VEGF-P/L组的平均卢瑟福分级和ABI有统计学意义的改善，但对照患者也有类似改善。我们得出结论，导管介导的VEGF基因疗法安全且耐受性良好。血管造影显示，VEGF-Ad组和VEGF-P/L组在PTA后通过VEGF基因转移均使血管增多。
