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

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.