上调的感应受体在肺高血压中调解肺静脉重塑
Qiudi Mo1,2,3, Xing Wen1,2, Luyao Wang1,2,4
1Department of Pulmonary and Critical Care Medicine in Hengqin Hospital, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China.
感应受体 (CaSR) 在肺高血压 (PH) 中的肺静脉重塑 (PVR) 中起着关键作用. 阻断CaSR减少PVR和PH的发展,提供了一个潜在的治疗点.
科学领域:
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
- 肺高血压研究 肺高血压研究
背景情况:
- 肺静脉改造 (PVR) 是肺高血压 (PH) 的重要因素,但其潜在机制尚未完全理解.
- 感应受体 (CaSR) 在PVR中的作用以前没有被研究过.
研究的目的:
- 在PH的实验模型中研究CaSR在PVR发展中的作用.
- 为了确定CaSR是否介导PH期间肺静脉中增强的 (Ca2+) 流入和光滑肌肉细胞增殖.
主要方法:
- 在使用单克罗他林 (MCT) 和缺氧 (HPH) 的老鼠中诱导了肺高血压.
- 人类肺静脉光滑肌细胞 (PVSMCs) 遭受过缺氧.
- 从PH模型和对照中,在PVSMC中评估了CaSR表达,Ca2+流入和细胞增殖.
- 使用药理抑制剂和向CaSR的小干扰RNA (siRNA) 来评估其功能.
主要成果:
- 在PH大鼠的远端肺静脉中观察到PVR,在PVSMC中增加了CaSR表达.
- 低氧在人类PVSMC中调高了CaSR和HIF-1α,促进了增殖和增加了细胞内Ca2+ ([Ca2+]i).
- CaSR激活增强了细胞外Ca2+诱导的[Ca2+]i和增殖;CaSR阻断减弱了这些效应,并防止了大鼠的PH发展.
结论:
- 升级的CaSR是PH中的PVR的关键调解者,通过增强的CaSR功能和细胞内Ca2+信号传递来促进PVSMC的扩散.
- 向CaSR是一种有希望的治疗策略,可以缓解PVR和PH的进展.
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