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在急性心肌梗塞中,长素PTX3的心脏保护功能
Monica Salio1, Stefano Chimenti, Noeleen De Angelis
1Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Circulation
|February 13, 2008
概括
长素PTX3在急性心肌梗塞期间保护心脏. 缺少PTX3的小鼠表现出心脏损伤恶化,表明其关键的心脏保护作用.
科学领域:
- 生物医学研究的研究.
- 心血管科学 心血管科学
- 炎症和免疫学 炎症和免疫学
背景情况:
- C-反应蛋白是缺血性心脏疾病的预后标志物,但由于物种差异,缺乏遗传验证.
- 长素PTX3在进化过程中被保存并在炎症期间在心脏中表达.
- PTX3是急性心肌梗塞 (AMI) 的潜在预后标志物.
研究的目的:
- 调查PTX3在急性心肌梗塞中的病原遗传作用.
- 确定PTX3在AMI的背景下是否具有保护功能.
主要方法:
- 使用一种由冠状动脉结合和再注射诱导的AMI小鼠模型.
- 评估PTX3表达和血后水平.
- 研究了PTX3缺乏 (ptx3-null小鼠) 对心脏损伤的影响.
- 给出异源PTX3来拯救表型.
主要成果:
- 在AMI后,PTX3表达和循环水平增加.
- PTX3 缺乏导致显著更大的心脏病发作 (33%的增加) 和恶化的心脏损伤.
- 缺乏PTX3与中性粒细胞透的增加,毛细血管密度的减少和心肌细胞亡的增加有关.
- 缺少PTX3的小鼠表现出高的互白素-6和补充C3沉积.
- 外源性PTX3给药逆转了在ptx3-null小鼠中观察到的有害影响.
结论:
- 在AMI中,PTX3起着关键的,非冗余的和调节性心脏保护作用.
- 在AMI中PTX3的保护功能涉及对补体级联的调制.
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