在肺动脉高血压中压力颗粒组装
Kosmas Kosmas1,2, Aimilia Eirini Papathanasiou1, Fotios Spyropoulos1
1Department of Pediatrics, Division of Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
压力颗粒 (SGs) 通过促进异常的血管表型和肌肉功能障碍,促进肺动脉高血压 (PAH). 减少SG形成可能是PAH的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
- 心血管研究研究心血管研究
背景情况:
- 肺动脉高血压 (PAH) 的发病因子仍然不完全理解.
- 压力颗粒 (SGs) 在PAH发展和进展中的作用目前尚不清楚.
- SGs是在细胞压力下形成的细胞质焦点,涉及各种疾病.
研究的目的:
- 调查压力颗粒 (SGs) 在肺动脉高血压 (PAH) 病变发生中的作用.
- 确定SG形成是否有助于PAH中的血管和肌肉功能障碍.
- 评估针对PAH中SG形成的治疗潜力.
主要方法:
- 使用PAH的鼠标苏根/缺氧 (SU/Hx) 模型.
- 检查了肺部,右心室和肌肉组织中的SG形成和蛋白质表达.
- 评估了乙胺 (ACTZ) 治疗对PAH和SG形成的影响.
- 研究了从老鼠和人类PAH模型中初级肺动脉光滑肌细胞 (PASMCs) 中SG抑制和G3BP1剥离的影响.
- 在人类PAH肺组织和PASMC中分析了GS的存在.
主要成果:
- 与对照者相比,SU/Hx大鼠在肺部,右心室和肌肉肌肉中增加了SG形成和蛋白质表达.
- 在所有受影响的组织中,ACTZ治疗改善了PAH症状,并减少了SG的形成.
- 由PAH衍生的PASMCs在氧化应激下增加了SG形成,而ACTZ可以逆转这种情况.
- 在PASMCs中抑制SG形成或G3BP1剥离改变了细胞表型,减少了增殖,增加了细胞亡,并调节了标记表达.
- 人类PAH肺部和PASMCs表现出增加的SG存在,而人类PAH-PASMCs中的G3BP1切除诱导了转向更可收缩的表型.
结论:
- 肺动脉光滑肌细胞 (PASMC) 和其他组织中增加的压力颗粒 (SG) 形成与肺动脉高血压 (PAH) 病原有关.
- 针对SG形成,可能通过G3BP1调制,可能为PAH提供一种新的治疗途径.
- SG形成是PAH中观察到的异常血管和细胞表型的重要贡献者.
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