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Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to prevent coronary microembolization-induced cardiac dysfunction

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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.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 81260042).

Author contributions

Qiang Su proposed and wrote the paper. All authors contributed to editing the final manuscript for content and style.

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Authors and Affiliations

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

    Q Su, L Li, Y Liu, Y Zhou, J Wang & W Wen

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  1. Q Su
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  2. L Li
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  3. Y Liu
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  4. Y Zhou
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  5. J Wang
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  6. W Wen
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Correspondence to L Li.

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This manuscript has not been published elsewhere in whole or in part. All authors have read and approved the content and agree to submit for consideration for publication in the journal. There is no ethical/legal conflicts involved in the article.

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Su, Q., Li, L., Liu, Y. et al. Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to prevent coronary microembolization-induced cardiac dysfunction. Gene Ther 22, 1000–1006 (2015). https://doi.org/10.1038/gt.2015.59

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