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Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice

靶向内皮PDK4-EndoMT反馈环路减轻小鼠胸主动脉夹层的发展

期刊: Arteriosclerosis, Thrombosis, and Vascular Biology 日期: 2026-03-19 PMID: 41853864 DOI: 10.1161/ATVBAHA.125.324031 浏览: 87
作者: Xiangyu Cao, Xingyou Guo, Haoyue Huang, Han Shen, Jingze Zhu, Yamei Gao, Anshu Liu, Tingyu Wang, Zeyu Xue, Chuanbin Tang, Lingqun Ye, Lianbo Shao, You Yu, Zhenya Shen
Cao, X., Guo, X., Huang, H., Shen, H., Zhu, J., Gao, Y., Liu, A., Wang, T., Xue, Z., Tang, C., Ye, L., Shao, L., Yu, Y., & Shen, Z. (2026). Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.125.324031
Cao X, Guo X, Huang H, Shen H, Zhu J, Gao Y, et al. Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 2026; doi: 10.1161/ATVBAHA.125.324031
Cao X, Guo X, Huang H, et al. Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice[J]. Arteriosclerosis, Thrombosis, and Vascular Biology. 2026. DOI: 10.1161/ATVBAHA.125.324031.
@article{cao2026,
  author = {Xiangyu Cao and Xingyou Guo and Haoyue Huang and Han Shen and Jingze Zhu and Yamei Gao and Anshu Liu and Tingyu Wang and Zeyu Xue and Chuanbin Tang and Lingqun Ye and Lianbo Shao and You Yu and Zhenya Shen},
  title = {Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice},
  journal = {Arteriosclerosis, Thrombosis, and Vascular Biology},
  year = {2026},
  doi = {10.1161/ATVBAHA.125.324031},
  note = {PMID: 41853864},
}
TY  - JOUR
AU  - Xiangyu Cao
AU  - Xingyou Guo
AU  - Haoyue Huang
AU  - Han Shen
AU  - Jingze Zhu
AU  - Yamei Gao
AU  - Anshu Liu
AU  - Tingyu Wang
AU  - Zeyu Xue
AU  - Chuanbin Tang
AU  - Lingqun Ye
AU  - Lianbo Shao
AU  - You Yu
AU  - Zhenya Shen
TI  - Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice
T2  - Arteriosclerosis, Thrombosis, and Vascular Biology
PY  - 2026
DO  - 10.1161/ATVBAHA.125.324031
AN  - PMID:41853864
ER  - 

摘要

胸主动脉夹层是一种高发病率和高死亡率的急性血管疾病。内皮细胞对维持血管稳态至关重要,但内皮-间充质转化在胸主动脉夹层中的作用尚不明确。PDK4(丙酮酸脱氢酶激酶4)作为这一病理细胞命运转换驱动因素的功能也未被阐明。本研究整合了人体主动脉标本和β-氨基丙腈诱导小鼠模型的转录组分析和免疫荧光分析,通过RNA测序和染色质免疫沉淀测定鉴定PDK4为内皮-间充质转化信号的关键下游效应因子。研究发现,转录因子SNAI1直接结合PDK4启动子激活其表达,过量的PDK4通过乳酸积累促进内皮-间充质转化,建立了PDK4-EndoMT正反馈环路。体内实验中,内皮特异性Pdk4过表达可自发引起主动脉夹层和破裂,而内皮Pdk4敲低或使用二氯乙酸药物抑制可减轻夹层进展,保持血管完整性并改善生存率。本研究突出了PDK4作为胸主动脉夹层治疗靶点的前景。

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