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解读内皮粒细胞巨-CSF在与艾滋病毒相关的慢性炎症中的作用
Soumya Panigrahi1, Elizabeth Mayne2, Susan Louw3
1Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
iScience
|October 11, 2024
概括
在HIV患者中,微生物产品增加葡萄糖吸收和粒细胞巨细胞殖民地刺激因子 (GM-CSF),导致内皮功能障碍. -葡萄糖共传输体-2 (SGLT2) 抑制剂可以通过减少这种炎症来提供治疗效益.
科学领域:
- 心血管生物学 心血管生物学
- 传染病免疫学 传染病免疫学
- 内皮细胞生物学 内皮细胞生物学
背景情况:
- 艾滋病毒感染者 (PWH) 往往由于慢性炎症和肠道屏障损伤导致内皮功能障碍 (ED).
- 在PWH中将微生物转移与ED联系起来的特定分子途径尚未完全理解.
研究的目的:
- 研究葡萄糖吸收和粒细胞巨细胞殖民地刺激因子 (GM-CSF) 在与艾滋病毒相关的内皮功能障碍中的作用.
- 探索-葡萄糖共运输体-2 (SGLT2) 抑制剂在缓解这些途径方面的治疗潜力.
主要方法:
- 在PWH的大动脉内皮质中评估了GM-CSF,托尔类受体-4 (TLR4) 和髓氧化酶的表达.
- 暴露初级人体内皮细胞的脂聚糖 (LPS) 来模仿细菌转位效应.
- 评估了SGLT2抑制剂对LPS激活细胞中的葡萄糖吸收,GM-CSF释放和ED的影响.
- 在SGLT2抑制剂的PWH中比较血GM-CSF度,而不是在药物上.
主要成果:
- PWH显示GM-CSF,TLR4和髓氧化酶的大动脉内皮表达增加.
- 低血压刺激增加了内皮细胞中的葡萄糖吸收和GM-CSF表达.
- 在LPS激活细胞中,SGLT2抑制剂降低了葡萄糖吸收,GM-CSF释放和ED.
- 使用SGLT2抑制剂的PWH与不使用这些抑制剂的非糖尿病PWH相比,具有较低的血GM-CSF水平.
结论:
- 微生物产品可能会驱动内皮糖摄取和GM-CSF表达,导致PWH的炎症和ED.
- SGLT2 抑制剂在向这些途径方面表现有前途,在PWH中具有潜在的治疗益处.
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