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通过激活血管光滑肌细胞转录因子EB,环素可以预防腹腔大动脉动脉瘤

Haocheng Lu¹, Jinjian Sun¹, Wenying Liang¹

¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor.

|May 2, 2020

概括

转录因子EB (TFEB) 通过抑制血管光滑肌细胞亡来保护腹腔大动脉瘤 (AAA). 用2-基-β-环氧激活TFEB可能为AAA提供一种新疗法.

科学领域:

血管生物学
分子医学
细胞平衡

背景情况:

腹主动脉动脉瘤 (AAA) 是一种危及生命的主动脉疾病,需要有效的药物治疗来防止扩张和破裂.
转录因子EB (TFEB) 是细胞过程的关键调节者,包括自和溶酶生物发生,对维持细胞健康至关重要.

研究的目的:

研究血管光滑肌细胞 (VSMC) 特定TFEB在AAA发育中的作用.
确定TFEB作为AAA治疗的潜在治疗点.

主要方法:

在人类和小鼠AAA样本中测量TFEB表达.
在VSMC和VSMC选择性Tfeb淘汰小鼠中使用功能损失/增益研究.
进行了转录组和功能分析以阐明TFEB的机制.
使用小鼠AAA模型来评估TFEB的体内功能和TFEB激活剂的影响.

主要成果:

在人类和小鼠的AAA病变中,TFEB表达减少.
部分通过上调B细胞淋巴瘤2来抑制VSMC亡.
在小鼠模型中,TFEB缺乏加剧了VSMC亡并促进了AAA形成.
通过依赖于VSMC的TFEB机制,TFEB激活剂2-基-β-环氧在小鼠中抑制了AAA的进展.

结论:

TFEB对VSMC细胞亡和AAA的发展起着保护作用.
TFEB激活是预防和治疗AAA的一个有前途的治疗策略.

关键词:

大动脉动脉瘤,腹部细胞亡自食症肌细胞,光滑肌肉

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