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用表达肝细胞生长因子的腺病毒载体进行心脏病发作后治疗,可以缓解老鼠的慢性左心室重塑和功能障碍
Yiwen Li1, Genzou Takemura, Ken-ichiro Kosai
1Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu 500-8705, Japan.
Circulation
|April 16, 2003
概括
肝细胞生长因子 (HGF) 基因疗法通过促进心肌细胞生长和减少纤维化,改善了心肌梗塞后的心脏功能. 这为心脏病发作后心力衰竭提供了新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 再生医学是一种再生医学.
- 基因治疗 基因治疗
背景情况:
- 肝细胞生长因子 (HGF) 在组织再生,血管生成和抗亡中发挥作用.
- HGF对心肌梗塞 (MI) 后左心室 (LV) 重塑和心力衰竭的慢性影响尚不清楚.
研究的目的:
- 调查HGF基因疗法的治疗潜力,以减轻心肌梗塞后不良的LV重塑和功能障碍.
主要方法:
- 在MI的小鼠模型中,由腺病毒介导的人类HGF (Ad.CAG-HGF) 输送到后肢肌肉.
- 在MI后4周评估LV重塑,功能,心脏病发作大小,心肌细胞缩,纤维化和细胞增殖/亡.
主要成果:
- 接受HGF治疗的小鼠表现出改善的LV重塑和功能,其特点是LV腔体较小,心脏/体重比较小,分数缩短增强,LV末端透气压力较低.
- 在接受HGF治疗的小鼠中观察到心肌细胞缩增加,心脏病发作壁较厚,血管密度更高,心室纤维化显著减少.
- 虽然心脏病发作的大小相似,但HGF治疗增强了c-Met/HGF受体表达,并促进了颗粒组织细胞增殖,减少了心脏病发作区域附近的亡.
结论:
- 发心后的HGF基因疗法有效地改善了LV重塑和心脏功能.
- 治疗效益归因于心肌细胞增大,心脏病发作壁的加厚,血管系统的保存和抗纤维作用.
- 这些发现表明HGF基因治疗是治疗心脏病发作后心力衰竭的有希望的新方法.
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