作为肺动脉高血压治疗的治疗点,CCR5
Valérie Amsellem1, Larissa Lipskaia1, Shariq Abid1
1Inserm U955 and Département de Physiologie, Hôpital Henri Mondor, Créteil, France, Université Paris-Est Créteil (UPEC), France.
Circulation
|July 5, 2014
概括
马拉维罗克向的CCR5通路,通过促进光滑肌肉细胞的增殖和炎症,在肺动脉高血压 (PH) 中发挥关键作用. 阻断CCR5为PH提供了潜在的新疗法,包括与艾滋病毒有关的病例.
科学领域:
- 心血管研究研究心血管研究
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 肺动脉高血压 (PH) 涉及复杂的血管改造,包括肺动脉光滑肌细胞 (PA-SMC) 增殖和炎症.
- 参与HIV进入的受体CCR5,在血管细胞和巨细胞上表达,可能有助于PH的发病.
研究的目的:
- 研究CCR5在肺动脉高血压 (PH) 的发展中的作用.
- 在实验PH模型中评估CCR5对抗的治疗潜力.
主要方法:
- 使用CCR5基因淘汰小鼠和人类CCR5淘汰小鼠进行CCR5抗剂maraviroc的药理学研究.
- 在低氧条件下评估PA-SMC增殖,巨细胞招募和PH发育.
- 研究了CCR5配体 (CCL5,HIV-1 gp120) 和maraviroc对PA-SMC和巨受条件介质的影响.
主要成果:
- 在PH肺部,CCR5表达升高,并局部化到PA-SMCs.
- 在低氧诱导的PH模型中,CCR5缺乏或用马拉维罗克阻塞降低了PA-SMC增殖和巨细胞的招募.
- 由CCL5和HIV-1gp120刺激的CCR5信号介导的PA-SMC生长,由maraviroc抑制的效果.
结论:
- CCL5-CCR5信号通路与PH病原发生有关.
- 针对CCL5-CCR5通路使用CCR5抗剂,如马拉维罗克,为PH提供了一个有前途的治疗策略,包括与艾滋病毒相关的病例.
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