在缺乏RESOLVIN D2受体GPR18的小鼠中,血管床特异性内皮功能障碍和年龄依赖的循环高血压
Sofie de Moudt1, Barbara Sitek2, Anna Bar2
1Université de Lorraine, Inserm, DCAC, Nancy, France.
概括
在老年小鼠中,G蛋白结合受体 (GPR) 18的缺失会导致血管功能障碍和高血压. GPR18信号传递对于维持内皮功能和调节血压至关重要,这表明了治疗潜力.
科学领域:
- 心血管生物学 心血管生物学
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- G蛋白结合受体 (GPR) 18 是RvD2.2等专门的亲溶解脂质介质 (SPM) 的受体.
- 包括RvD2在内的SPM在临床前模型中已证明在预防动脉样硬化方面具有有效性.
- GPR18信号传输对血管的直接影响仍然不完全理解.
研究的目的:
- 调查G蛋白结合受体 (GPR) 18信号传输对血管的直接影响.
- 确定GPR18在内皮功能和血压调节中的作用.
- 阐明GPR18.18的血管床特定功能.
主要方法:
- 使用了G蛋白结合受体 (GPR) 18淘汰赛 (KO) 和野生型 (WT) 鼠标.
- 在体内进行磁共振成像 (MRI) 进行内皮功能评估.
- 进行连续24小时远程测量以监测血压.
- 在隔离的血管中评估 ex vivo 血管反应性和免疫光.
主要成果:
- GPR18 KO小鼠在股骨动脉中表现出内皮功能障碍,其特征是受损的ACH诱导的血管扩张.
- 胸前大动脉的内皮功能没有受到影响,这表明血管床的特定影响.
- 在GPR18 KO小鼠的股骨动脉中观察到减少eNOS表达和增加因多美素敏感放松.
- 与WT小鼠相比,GPR18KO小鼠的白天平均动脉血压显著更高,这表明了年龄相关的高血压.
结论:
- 删除G蛋白结合受体 (GPR) 18导致血管床特定的内皮功能障碍.
- GPR18信号传输在维持血管平衡和调节血压方面发挥着至关重要的作用.
- 这些发现凸显了GPR18在衰老过程中对心血管的有益影响,并表明其作为治疗点的潜力.
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