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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
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微RNA-145向治疗可以减少动脉样硬化
Fina Lovren1, Yi Pan, Adrian Quan
1Division of Cardiac Surgery, Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada.
Circulation
|September 12, 2012
概括
在小鼠中进行的MicroRNA-145基因治疗减少了动脉样硬化斑块的大小,并促进了斑块的稳定性. 这表明microRNA-145是心血管疾病的潜在治疗点.
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.
- 基因治疗 基因治疗
背景情况:
- 微RNA是参与慢性疾病的基因表达的关键调节者.
- 微RNA-145 (miR-145) 在血管光滑肌细胞 (VSMC) 中高度表达,并影响其命运.
- 在动脉样硬化和斑块稳定性中miR-145的作用需要进一步研究.
研究的目的:
- 研究微RNA-145 (miR-145) 在调节动脉样硬化的治疗潜力.
- 为了确定VSMC特定的miR-145过度表达是否会影响动脉样硬化斑块的发育和体内稳定性.
主要方法:
- 在 Apolipoprotein E 淘汰赛 (ApoE(-/-)) 时,小鼠在 VSMC 特定的促进体 (SM22α) 或对照的 lentivirus 下,接受了表达 miR-145 的晶状病毒治疗.
- 给小鼠食西方饮食12周以诱导动脉样硬化.
- 对动脉样硬化病变进行了斑块大小,形态,细胞组成和VSMC表型标志物的分析.
主要成果:
- 针对SMC的miR-145输送显著减少了大动脉样硬化斑块的大小.
- 治疗增加了纤维状盖面积,原含量和VSMC标记物 (calponin,α-光滑肌动蛋白),同时减少了死核面积和巨细胞透.
- miR-145的过度表达降低了KLF4和增加了心肌表达,促进了收缩性VSMC表型.
结论:
- 特定于VSMC的miR-145过度表达是一种新的治疗策略,以限制动脉样硬化斑块的进展.
- 这种方法有效地改变了斑块形态和细胞组成,增强了稳定性并降低了破裂风险.
- miR-145作为治疗动脉样硬化和预防斑块破裂的目标具有前途.
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