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Introduction to the Ultrasound Targeted Microbubble Destruction Technique
Published on: June 12, 2011
Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to
1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Abstract:
The programmed cell death 4/nuclear factor-κB/tumor necrosis factor α (PDCD4/NF-κB/TNF-α) signaling pathway has an important role in coronary microembolization (CME)-induced inflammation. microRNA-21 protects myocardium mainly via regulation of its target gene PDCD4. Therefore, in this study we investigated the effect of ultrasound-guided microbubble-mediated microRNA-21 transfection on cardiac function in CME pig model and determined the potential mechanisms involved. The pig CME model was established by microcatheter-mediated injection of microembolization beads into the left anterior descending artery. The CME with microRNA transfection group was injected with plasmid-microbubble mixture through the marginal ear vein 4 days before CME treatment, along with ultrasound to the myocardium. Cardiac function indices were examined by cardiac ultrasound; infarct area was measured by hematoxylin-eosin and hematoxylin-basic Fuchsin-picric acid staining of tissue pathological sections; green fluorescent protein-labeled gene expression levels were evaluated by fluorescent microscopy in frozen sections; myocardial PDCD4 and TNF-α mRNA levels were measured by fluorescent quantitative PCR and protein levels were measured by western blotting; and NF-κB activity was tested by electrophoretic mobility shift assay. Compared with the CME group, the CME with ultrasound-mediated microRNA transfection group demonstrated improved CME-induced cardiac dysfunction (P<0.05). Compared with the CME group, the CME with ultrasound-mediated microRNA transfection group showed significantly lower PDCD4 expression and NF-κB activity (P<0.05). Ultrasound microbubble-mediated microRNA-21 transfection effectively improved CME-induced cardiac dysfunction via inhibition of PDCD4/NF-κB/TNF-α signal transduction pathway.
Insights
Ultrasound-guided microbubble delivery of microRNA-21 improved cardiac function in a coronary microembolization model. This therapy reduced inflammation by inhibiting the programmed cell death 4/nuclear factor-κB/tumor necrosis factor α pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Gene Therapy
Background:
- Coronary microembolization (CME) induces inflammation via the programmed cell death 4/nuclear factor-κB/tumor necrosis factor α (PDCD4/NF-κB/TNF-α) pathway.
- MicroRNA-21 (miR-21) plays a protective role in the myocardium by regulating its target gene, PDCD4.
Purpose of the Study:
- To investigate the therapeutic effects of ultrasound-guided microbubble-mediated miR-21 transfection on cardiac function in a pig model of CME.
- To elucidate the underlying mechanisms involving the PDCD4/NF-κB/TNF-α signaling pathway.
Main Methods:
- A pig model of CME was established using microcatheter-mediated injection of microembolization beads.
- miR-21 was delivered via plasmid-microbubble complexes combined with ultrasound therapy before CME induction.
- Cardiac function, infarct size, gene/protein expression (PDCD4, TNF-α), and NF-κB activity were assessed.
Main Results:
- Ultrasound-mediated miR-21 transfection significantly improved cardiac function in the CME model compared to the CME group (P<0.05).
- This intervention led to significantly reduced PDCD4 expression and NF-κB activity in the myocardium (P<0.05).
Conclusions:
- Ultrasound microbubble-mediated miR-21 transfection is an effective strategy to improve cardiac dysfunction caused by CME.
- The therapeutic benefits are achieved through the inhibition of the PDCD4/NF-κB/TNF-α signaling pathway.

