Stem Cell Center, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, USA.
J Card Fail. 2011 Jul;17(7):601-11. doi: 10.1016/j.cardfail.2011.03.004. Epub 2011 Apr 22.
Hepatocyte growth factor (HGF) may stimulate angiogenesis. We examined the safety and therapeutic potential of the HGF plasmid (VM202) in pigs with chronic myocardial ischemia.
We delivered VM202 or vehicle transendocardially to 4 groups of pigs: vehicle control (n = 9); high-dose VM202 (n = 9); low-dose VM202 (n = 3); and normal control (no ischemia; n = 1). Pigs were killed 3, 30, and 60 days after injection. No adverse events were associated with VM202 treatment or delivery. Quantitative polymerase chain reaction indicated that heart injection sites had the highest levels of VM202 (day 3), which became almost undetectable by 30-60 days. Most nontarget tissues showed clearance of VM202 plasmid by day 30. Control and VM202-treated pigs did not differ in global functional data. Dobutamine-stressed myocardial-contrast echocardiogram suggested that VM202 may help preserve microvascular perfusion at 30 days; reperfusion velocity in ischemic myocardium decreased significantly in control (baseline to follow-up, 5.1 ± 1.9 to 2.7 ± 1.0; P = .031) but not in VM202 groups (high-dose: 3.1 ± 1.1 vs 3.1 ± 1.5 [P = .511]; low-dose: 3.8 ± 1.1 vs 3.9 ± 1.5 [P = .559]). Linear local shortening increased significantly from day 0 to 30 in VM202-treated versus control pigs (5.0 ± 4.7% vs 9.2 ± 7.5% vs 0.9 ± 5.8% [high-dose, low-dose, control, respectively]; P = .021).
Transendocardial delivery of VM202 was safe and may help to preserve microcirculatory perfusion and improve wall motion.
肝细胞生长因子（HGF）可能刺激血管生成。我们研究了 HGF 质粒（VM202）在患有慢性心肌缺血的猪中的安全性和治疗潜力。
我们通过心内膜向 4 组猪给药：载体对照组（n=9）；高剂量 VM202 组（n=9）；低剂量 VM202 组（n=3）；正常对照组（无缺血；n=1）。注射后 3、30 和 60 天处死猪。VM202 治疗或给药与任何不良事件无关。定量聚合酶链反应表明，心脏注射部位的 VM202 水平最高（第 3 天），30-60 天后几乎检测不到。大多数非靶组织在第 30 天清除了 VM202 质粒。对照和 VM202 处理的猪在整体功能数据上没有差异。多巴酚丁胺应激心肌对比超声心动图表明，VM202 可能有助于在 30 天时保留微血管灌注；对照组缺血心肌的再灌注速度明显下降（从基线到随访，5.1±1.9 至 2.7±1.0；P=0.031），而 VM202 组则没有（高剂量：3.1±1.1 与 3.1±1.5[P=0.511]；低剂量：3.8±1.1 与 3.9±1.5[P=0.559]）。VM202 治疗的猪与对照猪相比，从第 0 天到第 30 天的线性局部缩短显著增加（分别为 5.0±4.7%、9.2±7.5%和 0.9±5.8%[高剂量、低剂量、对照]；P=0.021）。
心内膜内递送 VM202 是安全的，可能有助于维持微循环灌注和改善壁运动。
