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PDGF-BB/EGR1轴驱动纤维细胞激活蛋白表达以促进腹腔大动脉动脉瘤

Zhihao Zhou¹, Lin Huang², Hui Luo³

¹Division of Vascular Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510800, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

International journal of medical sciences

|June 16, 2025

概括

纤维细胞激活蛋白 (FAP) 在腹腔大动脉动脉瘤 (AAA) 发育期间在血管光滑肌细胞中升级. 针对PDGF-BB/EGR1/FAP途径可能为AAA提供新的治疗策略.

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.
血管生物学血管生物学

背景情况:

腹腔大动脉瘤 (AAA) 是一种危及生命的疾病,具有复杂的分子基础.
血管光滑肌细胞 (VSMCs) 在AAA病变发生过程中发挥着关键作用.
在AAA中驱动VSMC功能障碍的精确分子机制仍然不完全理解.

研究的目的:

在AAA开发过程中调查纤维细胞激活蛋白 (FAP) 在VSMC中的作用.
阐明调节VSMC中的FAP表达的分子信号通路.
评估在AAA中准FAP的治疗潜力.

主要方法:

批量和单细胞RNA测序的AAA衍生的VSMCs.
猪胰腺弹性酶 (PPE) 诱导的AAA小鼠模型.
药理上抑制FAP和转录因子EGR1.
临床的18F-FAP抑制剂PET/CT成像.

主要成果:

在AAA衍生的VSMC中,FAP表达显著升高.
在小鼠模型中,FAP抑制减弱了动脉瘤的形成和减少了巨细胞的透.
通过EGR1-介导的转录激活,PDGF-BB通过EGR1-介导的转录激活在VSMC中调节FAP表达.
临床成像证实了感染性AAA患者的高FAP表达.

结论:

PDGF-BB/EGR1/FAP信号轴是AAA病变发生的一个关键驱动器.
准FAP为管理AAA提供了一个有前途的治疗策略.
FAP作为AAA活动的潜在生物标志物.

关键词:

腹腔大动脉动脉瘤腹腔大动脉动脉瘤纤维细胞激活蛋白质的激活蛋白质血管光滑肌肉细胞.血管光滑肌肉细胞.

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