Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to

Q Su1, L Li1, Y Liu1

  • 1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Gene Therapy
|June 17, 2015
PubMed

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.

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