胰岛素需要酶1通路和自驱动内皮细胞对发烧范围高温的连续反应
Julie Vorbe1,2, Florence Massey3, Corinne Rocher3
1Université Paris Cité and Université Sorbonne Paris Nord, INSERM, LVTS, F-75018, Paris, France.
PloS one
|May 7, 2025
概括
发烧范围高温症通过激活IRE1α-自途径损害冠状动脉内皮细胞,导致细胞功能障碍. 抑制IRE1α可以保护这些重要的心脏细胞.
科学领域:
- 心血管生物学 心血管生物学
- 细胞生理学 细胞生理学
- 分子医学是分子医学.
背景情况:
- 发烧是对感染的适应性反应,但长期发烧会导致有害影响.
- 感染和长期发烧与致命的心脏不良事件有关,特别是冠状动脉循环受损.
- 高温对冠状动脉微循环功能障碍的直接影响需要进一步阐明.
研究的目的:
- 研究人类冠状动脉内皮细胞 (HCAECs) 对发烧范围高温的特定细胞和分子反应.
- 阐明冠状动脉微循环中温度诱导的功能障碍背后的机制.
- 确定潜在的治疗目标,以减轻与发烧有关的心脏并发症.
主要方法:
- 人类冠状动脉内皮细胞 (HCAECs) 被暴露在37°C或40°C中长达24小时.
- 转录组和蛋白组分析 (微阵列,质谱) 在6小时,12小时和24小时进行.
- 使用机械方法确定和验证了信号通路,调节器和机制.
主要成果:
- 长时间的高温 (40°C) 损害了HCAEC功能,导致细胞脱离,结节损失和透性增加.
- HCAECs激活了展开的蛋白质反应 (UPR),包括IRE1α激活和XBP1拼接.
- 增高的自流降解了连接蛋白;药理 IRE1α 抑制减轻了这些影响并保持了细胞完整性.
结论:
- IRE1α-自轴对于调节发烧范围高温下冠状动脉内皮细胞存活和功能至关重要.
- 这种机制在感染引起的发烧期间有助于内皮功能障碍,可能与局部炎症条件有关.
- 针对IRE1α-自途径提供了一种潜在的策略,可以在发烧和炎症期间保护心脏.
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