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胆固醇血酸在心血管疾病患者中存在引起小鼠纤维细胞中的溶酶体功能障碍

Elizeth Lopes¹, Gisela Machado-Oliveira¹, Catarina Guerreiro Simões¹

¹iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1150-069 Lisbon, Portugal.

|December 22, 2023

概括

胆固醇半酸盐 (ChA) 破坏纤维细胞溶解体的功能,抑制自并导致细胞死亡. 这表明,ChA通过损害纤维细胞中的这些重要细胞过程,有助于动脉样硬化的进展.

科学领域:

心血管生物学心血管生物学
细胞病理生理学
动脉样硬化研究动脉样硬化研究

背景情况:

纤维细胞在动脉样硬化和斑块形成中发挥着至关重要的作用.
氧化脂质,包括胆固醇半 (ChE),在动脉样硬化病变中积聚.
cholesteryl hemiazelate (ChA) 是一种普遍存在的 ChE,它会损害巨细胞和血管光滑肌细胞中的 lysosome 功能.

研究的目的:

为了研究CHA对纤维细胞溶解体功能和细胞平衡的影响.
为了阐明在纤维细胞中ChA诱导的溶酶体功能障碍的下游后果.
为了确定CHA诱导的纤维细胞功能障碍是否有助于动脉样硬化病原.

主要方法:

用CHA治疗人类纤维细胞.
溶解体形态和脂质积累的显微镜分析.
评估溶酶体生物发生,TFE3转录,自,mTORC1激活和纤维细胞亡.

主要成果:

A治疗导致纤维细胞中扩大,脂质载的溶酶体的周核积累.
没有诱导de novo lysosome生物发生,只有轻微的TFE3上调.
自被抑制,可能是通过mTORC1激活,导致纤维细胞亡.

结论:

在纤维细胞中,ChA会诱导溶解体功能障碍和亡,类似于它对其他细胞类型的影响.
纤维细胞中的 lysosome 功能受损和自是导致动脉样硬化的新机制.
向纤维细胞中ChA介导的细胞损伤可能为动脉样硬化提供治疗策略.

关键词:

动脉样硬化动脉样硬化自和亡是自和亡的过程.胆固醇半乙酸盐是什么胆固醇乙基半的使用方法溶酶体功能障碍溶酶体功能障碍在小鼠胚胎纤维细胞中.

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