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抗单细胞化学吸引蛋白-1基因疗法减轻了实验性心肌梗塞后的左心室重塑和失败
Shunji Hayashidani1, Hiroyuki Tsutsui, Tetsuya Shiomi
1Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Circulation
|October 1, 2003
概括
单细胞化学吸引蛋白-1 (MCP-1) 的激活在心肌梗塞 (MI) 后加剧心力衰竭. 用基因疗法阻断MCP-1改善了MI小鼠的存活率,并减少了心脏重塑.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 再生医学是一种再生医学.
背景情况:
- 单细胞化学吸引蛋白-1 (MCP-1) 的表达在失败的心脏中升高.
- 在心肌梗塞 (MI) 后心力衰竭的病理生理学中MCP-1的作用尚未完全理解.
研究的目的:
- 为了研究心脏中风后心脏中MCP-1水平.
- 为了确定阻断MCP-1是否可以防止左心室 (LV) 重塑和衰竭.
主要方法:
- 小鼠通过冠状动脉绑定进行MI诱导.
- 使用基因疗法阻断了MCP-1信号传递,该疗法是将人类MCP-1基因的N终端删除突变输送到骨肌肉.
- 在MI后4周评估了LV功能,重塑,纤维化,巨细胞透和基因表达.
主要成果:
- 在非心脏病发作的LV后MI中,MCP-1 mRNA水平显著增加.
- 阻断MCP-1改善了生存率 (61%对87%) 和减弱了 LV 扩张,收缩功能障碍和间歇性纤维化.
- 在接受治疗的MI小鼠中观察到减少巨细胞的招募和抑制TNF-α和TGF-β的表达.
结论:
- 激活MCP-1是LV重塑和MI后失败的关键因素.
- 反MCP-1基因疗法是预防心脏病发作后心力衰竭的一个有希望的策略.
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