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诱导腹腔大动脉瘤的发展和进展
Daniel Y Li1, Albert Busch1, Hong Jin2
1Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar (D.Y.L., A. Busch, J.P., S.L., H.-H.E., L.M.), Technical University Munich, and German Center for Cardiovascular Research (DZHK), partner site Munich, Germany.
Circulation
|April 20, 2018
概括
长非编码RNA H19 调节腹腔大动脉瘤发育中的平滑肌细胞存活率. 抑制H19可能为大动脉动脉瘤疾病提供新的治疗策略.
科学领域:
- 分子生物学
- 遗传学
- 心血管研究
背景情况:
- 长非编码RNAs (lncRNAs) 是生物过程和疾病的关键调节者.
- 腹腔大动脉瘤 (AAA) 的发展涉及复杂的分子机制.
- 在AAA病变发生过程中识别新型lncRNA对于治疗开发至关重要.
研究的目的:
- 鉴定和功能性表征动脉动脉瘤 (AAA) 发展中的 lncRNA.
- 研究 lncRNA H19 在 AAA 发病过程中的作用.
- 探索H19作为AAA的潜在治疗目标.
主要方法:
- 在两种小鼠AAA模型中分析RNA转录表达 (Angiotensin II输注和猪胰腺弹性酶灌注).
- 定量逆转录聚合酶链反应和现场杂交以确认H19的表达.
- 在体内和体外实验中使用反感性寡核酸 (LNA-GapmeRs) 来对平滑肌细胞 (SMCs) 进行H19敲击和过度表达.
- 分析H19的下游因子,包括低氧诱导因子1α (HIF-1α) 和p53.
主要成果:
- 在这两种小鼠AAA模型中, lncRNA H19 显著上调.
- 在实验中,对H19的抑制减少了动脉瘤的生长和SMC的亡.
- H19过度表达在体外增加了SMC亡,独立于miR-675.
- H19 与细胞质中的HIF-1α相互作用,导致p53稳定和SMC亡的增加.
- H19通过招募特异性蛋白1来促进HIF-1α转录.
结论:
- 在腹腔大动脉瘤的发展和进展中, lncRNA H19 是SMC存活和亡的新型调节者.
- 在AAA的发病过程中,H19起着至关重要的作用.
- 抑制H19代表了对大动脉动脉瘤疾病的潜在新型分子治疗策略.
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