向CR2的单细胞导向RNAi改善了动脉样硬化易患小鼠的心脏病愈合
Maulik D Majmudar1, Edmund J Keliher, Timo Heidt
1Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA. mnahrendorf@mgh.harvard.edu
Circulation
|April 26, 2013
概括
用RNAi向CR2可降低小鼠心肌梗塞 (MI) 后的炎症. 这种方法改善了心脏功能,并防止了不良的心脏重塑,为后心脏病发作心力衰竭提供了潜在的治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 免疫学 免疫学 免疫学
- 分子医学是分子医学.
背景情况:
- 心肌梗塞 (MI) 后的长期炎症加剧了心脏重塑和心力衰竭.
- 准炎症途径是一种潜在的治疗策略,但最佳时间和监测尚不清楚.
- 需要非侵入性监测工具来指导心脏病发作后的抗炎干预措施.
研究的目的:
- 为了研究纳米粒子促进的CCR2沉默在减少后心脏病发作炎症的治疗潜力.
- 开发和使用双目标PET/MRI用于监测炎症和矩阵交叉链接.
- 评估CCR2抑制对心脏功能和心脏中风后重塑的影响.
主要方法:
- 使用了受到MI的阿波利波蛋白E缺陷 (apoE(-/-)) 小鼠.
- 用纳米颗粒封装的siRNA向CCR2,以减少Ly-6C (高) 单细胞流量.
- 采用双目标正子发射断层扫描/磁共振成像 (PET/MRI) 来监测髓氧化酶 (MPO) 活性和XIII因子 (FXIII) 交联.
- 通过流细胞计,基因表达和组织学评估心脏功能 (排泄分数) 和炎症.
主要成果:
- 纳米粒子介导的CCR2沉默显著减少了心脏梗塞中单细胞透和炎症.
- 双标PET/MRI成功可视化了抗炎作用 (75%降低MPO信号) 和不受阻碍的矩阵交叉链接.
- 向的RNAi疗法在MI后的21日改善了喷射分数,从29%提高到35%.
- 组织学和基因表达证实了减少炎症和增强分辨率.
结论:
- 针对CCR2的RNAi有效地减少了Ly-6C (高) 单细胞的招募和心脏病发作炎症.
- 非侵入性PET/MRI监测准确地反映了抗炎治疗效果和矩阵愈合.
- 沉默CCR2减弱了心脏病后的左心室重塑,并改善了心脏功能.
相关概念视频
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...