高脂肪刺激通过TPM1/P53/SHISA5轴诱导心脏结构重塑
Yansong Cui1, Shuting Bai2, Zhenlin Liu2
1Department of Cardiology, Cheeloo College of Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Lipids in health and disease
|April 12, 2025
概括
高脂水平通过细胞外囊泡增加热素1 (TPM1),激活P53/SHISA5通路,并诱导ER压力和自,促进心房纤维化. 这种机制有助于心房重塑和心房的进展.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 前庭结构改造是心房动 (AF) 发展和进展的核心.
- 超脂血是AF的潜在贡献者,通过各种途径影响心脏功能.
研究的目的:
- 调查高脂水平促进AF进展的机制.
- 阐明热素1 (TPM1) 和P53/SHISA5信号轴在脂质诱导的心房重塑中的作用.
主要方法:
- 使用了体外细胞模型 (棕酸刺激) 和体内大鼠模型 (高脂肪饮食).
- 进行了蛋白质组,转录组,细胞外囊泡 (EV) 隔离和自分析.
- 蛋白质表达通过免疫阻塞,免疫组织化学和免疫光学来评估.
主要成果:
- 高脂刺激增加了心肌细胞中的TPM1表达,通过EV转移到心脏纤维细胞,激活P53/SHISA5轴.
- 这种激活诱导了内质网膜 (ER) 应激和自,促进了心房结构重塑.
- 在人类心脏纤维细胞和HFD养大鼠中的SHISA5过度表达减少了ER压力,自和纤维化.
结论:
- 高脂肪刺激通过调节ER压力和自,通过TPM1/P53/SHISA5轴诱导心脏纤维化.
- TPM1/P53/SHISA5轴代表了管理与高脂血症相关的AF进展的潜在治疗目标.
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