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内皮衍生的神经素保护心脏免受缺血性损伤
Nadia Hedhli1, Qunhua Huang, April Kalinowski
1Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Circulation
|May 11, 2011
概括
内皮细胞 (EC) 释放神经调节素 (NRG) 来保护心脏细胞免受伤害. 这一发现突出了NRG作为潜在的治疗心脏病的目标.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传递 细胞信号传递
- 再生医学是一种再生医学.
背景情况:
- 心脏内皮细胞 (EC) 对于心脏功能至关重要,但它们的保护作用的媒介是未知的.
- 由EC产生的生长因子神经调节素 (NRG) 与心脏肌细胞受体 (erbB) 相互作用.
- 来自EC的因素涉及到心脏的自克林/克林调节.
研究的目的:
- 研究心脏内皮细胞 (EC) 产生的神经调节素 (NRG) 在保护心脏肌细胞免受缺血损伤方面的作用.
- 为了确定NRG是否调解EC的心脏保护作用.
主要方法:
- 在低氧-重氧化下,从人类心脏EC中评估NRG释放.
- 研究了NRG对孤立成年心室肌细胞的亡的影响.
- 在欧洲共同体中利用了共同培养系统和NRG的基因操纵 (删除/沉默).
- 研究了内皮选择性NRG删除对整体器官制剂和冠状动脉绑定后缺血性耐受性的体内影响.
主要成果:
- 人类心脏EC释放NRG作为对低氧-重氧化的反应.
- NRG显著降低了经过缺氧复氧化的心脏肌细胞的亡.
- 通过EC介导的对亡的保护取决于NRG的表达.
- 在体内内,内皮特异性的NRG缺失会影响缺血损伤的恢复,并增加心脏病发作的大小.
结论:
- 内皮细胞衍生的神经调节素 (NRG) 是心脏肌细胞保护免受缺血损伤的关键调节剂.
- 准NRG信号通路为治疗心脏病提供了潜在的临床策略.
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