氧化LDL诱导的FOXS1调解胆固醇运输功能障碍和炎症酶激活,以驱动大动脉结石化
Chen Jiang1, Dingyi Yao1,2, Qiang Shen1
1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, Hubei 430022, China.
Cardiovascular research
|September 24, 2025
概括
这项研究揭示了由氧化LDL激活的转录因子FOXS1通过破坏胆固醇运输和激活膜细胞中的炎症来驱动状动脉病 (CAVD) 的进展.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 生物化学 生物化学
背景情况:
- 动脉疾病 (CAVD) 是与人口老龄化相关的日益严重的公共卫生问题.
- 目前对CAVD的治疗方法有限,这凸显了对新型治疗点的需求.
- 低密度脂蛋白 (LDL) 通过炎症和化在CAVD病原发生中起作用,但潜在的机制需要进一步研究.
研究的目的:
- 确定大动脉结石化的关键分子调节者.
- 阐明转录因子FOXS1在CAVD发展中的作用.
- 探索针对FOXS1-介导途径的治疗策略.
主要方法:
- 使用了人类膜间歇细胞 (VIC) 和高脂肪饮食养的Apoe-/-Foxs1-/-小鼠模型.
- 采用大量RNA测序,qRT-PCR,西斑,小干扰RNA和染色体免疫沉测序.
- 研究了基因调节,骨质分化,胆固醇运输和炎症酶激活.
主要成果:
- 确定FOXS1是大动脉结石化的关键调节者,由VIC中氧化LDL (oxLDL) 诱导.
- 证明FOXS1删除在体内显著降低了大动脉的化.
- 发现FOXS1通过BSCL2/PPARγ/LXRα轴抑制ABCA1和ABCG1的表达,导致胆固醇积累和NLRP3炎症酶激活.
结论:
- 转录因子FOXS1通过破坏胆固醇运输和激活VICs中的NLRP3炎症酶来促进CAVD.
- 针对FOXS1或其下游效应器,如BSCL2,可能为CAVD提供新的治疗途径.
- 这些发现为推动CAVD进展的分子机制提供了更深入的理解.
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