title: 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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: W
authors.initials: W
authors.lastname: Wen
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000517:prevention & control* / Q000628:therapy; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control* / Q000628:therapy; D003331:Coronary Vessels / Q000378:metabolism; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D045423:Microbubbles; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha