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微RNA-146a通过抑制VSMC炎症来防止AAA的发展

Wei-Peng Hu^1,2,3,4,5, Yu-Tsung Shih⁶, Qin-Yu Wang^1,2

¹Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-P.H., Q.-Y.W., H.-Y.M., Q.-Y.Z., Z.-Y.C., R.Q.).

Hypertension (Dallas, Tex. : 1979)

|October 31, 2025

概括

微RNA 146a (miR-146a) 通过维持血管光滑肌细胞 (VSMC) 恒常性来预防腹腔大动脉动脉瘤 (AAA). 在主动脉中抑制miR-146a为AAA提供了一个有前途的治疗策略.

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.
遗传学和基因组学遗传学和基因组学

背景情况:

血管光滑肌细胞 (VSMC) 稳态对于预防腹腔大动脉动脉瘤 (AAA) 至关重要.
微RNA 146a (miR-146a) 水平在AAA患者中发生变化,但其在VSMC恒温和AAA发展中的具体作用尚不清楚.

研究的目的:

调查miR-146a在维护VSMC平衡中的作用.
确定miR-146a对腹腔大动脉动脉瘤 (AAA) 的发展和进展的影响.

主要方法:

评估了AAA小鼠模型的血和大动脉中的miR-146a表达.
使用ApoE-/- MiR-146a-/-双淘汰赛小鼠来评估AAA的进展.
采用转录组学分析来阐明miR-146a在VSMC恒温中的机制.
使用miR-146a模仿和TNFα刺激进行的体外实验.

主要成果:

在患者和小鼠模型的动脉瘤组织内,VSMC中的MiR-146a表达升高.
在ApoE-/-小鼠中,miR-146a的淘汰会加剧AAA的发生率和严重程度.
miR-146a模仿抑制了TNFα诱导的VSMC炎症,亡和脱差.
miR-146a通过减少IRAK-1和TRAF-6来抑制NF-κB/NLRP3信号通路.
当地给予miR-146a时,agomir在体内抑制了AAA扩张.

结论:

米R-146a通过维护VSMC平衡,对AAA的形成和进展起着保护作用.
在主动脉中抑制miR-146a,为限制AAA扩张提供了潜在的治疗途径.

关键词:

腹部大动脉动脉瘤腹部大动脉动脉瘤灭症 (apoptosis) 是一种死亡的过程.这是一种炎症炎症炎症炎症.微型RNA146 146 是一个微型RNA.顺肌细胞是平滑肌肉的细胞.

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MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...