• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Gene therapy with hypoxia-inducible factor 1 alpha in skeletal muscle is cardioprotective in vivo.
【24h】

Gene therapy with hypoxia-inducible factor 1 alpha in skeletal muscle is cardioprotective in vivo.

机译：在骨骼肌中用缺氧诱导因子1α进行基因治疗具有心脏保护作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

AIMS: Gene therapy of a peripheral organ to protect the heart is clinically attractive. The transcription factor hypoxia-inducible factor 1 alpha (HIF-1alpha) transactivates cardioprotective genes. We investigated if remote delivery of DNA encoding for HIF-1alpha is protective against myocardial ischemia-reperfusion injury in vivo. MAIN METHODS: DNA encoding for human HIF-1alpha was delivered to quadriceps muscles of mice. One week later myocardial infarction was induced and four weeks later its size was measured. Echocardiography and in vivo pressure-volume analysis was performed. Coronary vascularization was evaluated through plastic casting. HL-1 cells, transfected with either HIF-1alpha or HMOX-1 or administered bilirubin or the carbon monoxide (CO) donor CORM-2, were subjected to lipopolysacharide (LPS)-induced cell death to compare the efficacy of treatments. KEY FINDINGS: After four weeks of reperfusion post infarction, animals pretreated with HIF-1alpha showed reduced infarct size and left ventricular remodeling (p<0.05, respectively). Fractional shortening was preserved in mice pretreated with HIF-1alpha (p<0.05). Invasive hemodynamic parameters indicated preserved left ventricular function after HIF-1alpha (p<0.05), which also induced coronary vascularization (p<0.05). HIF-1alpha downstream target heme oxygenase 1 (HMOX-1) was upregulated in skeletal muscle, while serum bilirubin was increased. Transfection of HL-1 cells with HIF-1alpha or HMOX-1 and administration of bilirubin or CORM-2 comparably salvaged cells from lipopolysacharide (LPS)-induced cell death (all p<0.05). SIGNIFICANCE: HIF-1alpha gene delivery to skeletal muscle preceding myocardial ischemia reduced infarct size and postischemic remodeling accompanied by an improved cardiac function and vascularization. Similar to HIF-1alpha, HMOX-1, bilirubin and CO were protective against LPS-induced injury. This observation may have clinical potential.
机译：目的：保护心脏的外周器官基因治疗在临床上具有吸引力。转录因子缺氧诱导因子1α（HIF-1alpha）激活心脏保护基因。我们研究了编码HIF-1alpha的DNA的远程递送是否对体内的心肌缺血-再灌注损伤具有保护作用。主要方法：编码人类HIF-1alpha的DNA被传递到小鼠的股四头肌。一周后诱发心肌梗塞，四周后测量其大小。进行超声心动图和体内压力容量分析。通过塑料铸件评估冠状动脉血管形成。用HIF-1α或HMOX-1或施用的胆红素或一氧化碳（CO）供体CORM-2转染的HL-1细胞经受脂多糖（LPS）诱导的细胞死亡，以比较治疗效果。主要发现：梗死后再灌注四周后，用HIF-1α预处理的动物显示梗死面积缩小和左心室重构（分别为p <0.05）。在用HIF-1alpha预处理的小鼠中保留了部分缩短（p <0.05）。有创血流动力学参数表明HIF-1alpha后左心室功能得以保留（p <0.05），这也引起了冠状动脉血管化（p <0.05）。 HIF-1alpha下游目标血红素加氧酶1（HMOX-1）在骨骼肌中被上调，而血清胆红素则在增加。用HIF-1α或HMOX-1转染HL-1细胞以及施用胆红素或CORM-2可以挽救从脂多糖（LPS）诱导的细胞死亡中挽救的细胞（所有p <0.05）。意义：HIF-1alpha基因在心肌缺血前向骨骼肌的传递减少了梗死面积和缺血后重塑，同时改善了心脏功能和血管生成。与HIF-1alpha类似，HMOX-1，胆红素和CO对LPS诱导的损伤具有保护作用。这种观察可能具有临床潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号