MicroRNA Profiling of Atrial Fibrillation in Canines: MiR-206 Modulates Intrinsic Cardiac Autonomic Nerve Remodeling by Regulating SOD1
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{"title"=>"MicroRNA profiling of atrial fibrillation in canines: MiR-206 modulates intrinsic cardiac autonomic nerve remodeling by regulating SOD1", "type"=>"journal", "authors"=>[{"first_name"=>"Yujiao", "last_name"=>"Zhang", "scopus_author_id"=>"55262642300"}, {"first_name"=>"Shaohua", "last_name"=>"Zheng", "scopus_author_id"=>"55968327900"}, {"first_name"=>"Yangyang", "last_name"=>"Geng", "scopus_author_id"=>"56574686100"}, {"first_name"=>"Jiao", "last_name"=>"Xue", "scopus_author_id"=>"55929709300"}, {"first_name"=>"Zhongsu", "last_name"=>"Wang", "scopus_author_id"=>"54407581300"}, {"first_name"=>"Xinxing", "last_name"=>"Xie", "scopus_author_id"=>"55614193300"}, {"first_name"=>"Jiangrong", "last_name"=>"Wang", "scopus_author_id"=>"54407712200"}, {"first_name"=>"Shuyu", "last_name"=>"Zhang", "scopus_author_id"=>"36867639100"}, {"first_name"=>"Yinglong", "last_name"=>"Hou", "scopus_author_id"=>"15750476200"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"25816284", "doi"=>"10.1371/journal.pone.0122674", "pui"=>"604134894", "issn"=>"19326203", "sgr"=>"84929492983", "scopus"=>"2-s2.0-84929492983"}, "id"=>"37cf270b-298e-3635-a7af-ce9873acce3d", "abstract"=>"BACKGROUND A critical mechanism in atrial fibrillation (AF) is cardiac autonomic nerve remodeling (ANR). MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Numerous miRNAs are involved in diseases of the nervous and cardiovascular systems. OBJECTIVE We aimed to assess the underlying role of miRNAs in regulating cardiac ANR in AF by right atrial tachypacing (A-TP) in canines. METHODS AND RESULTS Following 4-week A-TP, the superior left ganglionated plexuses (SLGPs), which are embedded in the fat pads of the left atrium, were subjected to miRNA expression profiling to screen preferentially expressed miRNAs. Sixteen miRNAs showed significantly differential expression between the control and A-TP groups, including miR-206, miR-203, miR-224 and miR-137. In particular, we focused on miR-206, which was elevated ~10-fold in A-TP dogs. Forced expression of miR-206 through lentiviral infection based on A-TP in vivo significantly shortened the atrial effective refractory period (AERP) (81 ± 7 vs. 98 ± 7 ms, P < 0.05). Immunohistochemical analysis showed that the regeneration of nerves increased more than 2-fold by miR-206 overexpression (P < 0.01). The expression of superoxide dismutase 1 (SOD1) was repressed by miR-206 overexpression by Western blot and luciferase assay, indicative of SOD1 as a direct target of miR-206. Overexpression of miR-206 increased reactive oxygen species (ROS) levels in vitro and in vivo, whereas miR-206 silencing attenuated irradiation- or A-TP-induced ROS. Knockdown of SOD1 effectively abolished ROS reduction caused by miR-206 silencing. CONCLUSIONS Our results found the differential expression of miRNAs in response to ANR in AF and elucidated the important role of miR-206 by targeting SOD1. The study illustrated the novel molecular mechanism of ANR and indicated a potential therapeutic target for AF.", "link"=>"http://www.mendeley.com/research/microrna-profiling-atrial-fibrillation-canines-mir206-modulates-intrinsic-cardiac-autonomic-nerve-re", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>3, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>3, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>2, "Veterinary Science and Veterinary Medicine"=>4, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"Turkey"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1992901"], "description"=>"<p>(A) The canine myocardial cells were infected with lenti-RNAi-NC or lenti-RNAi-SOD1. 48 h after infection, cells were collected and SOD1 and internal standard GAPDH protein levels were detected by Western blot. **<i>P</i> < 0.01. (B) Determination of ROS levels of canine primary myocardial cells infected with indicated lentiviruses. Cells were infected with lenti-control, lenti-RNAi-NC, lenti-anti-miR-206 or lenti-RNAi-SOD1. To induce ROS, cells were exposed to 10 Gy X-ray irradiation. 48 h after infection, the ROS levels were determined. Representative images in each group by a fluorescence microscope were under the same condition. (C) Relative ROS levels in indicated groups were calculated. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and N.S: not statistically significant.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359163, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.g006", "stats"=>{"downloads"=>2, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_206_regulated_ROS_via_SOD1_in_canine_primary_myocardial_cells_/1359163", "title"=>"miR-206 regulated ROS via SOD1 in canine primary myocardial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992895"], "description"=>"<p>(A) Immunohistochemical staining of PGP9.5-positive nerves in the SLGPs in the lenti-control, lenti-miR-206, A-TP, A-TP plus lenti-miR-206 and A-TP plus lenti-anti-miR-206 groups separately. (B) TH-positive nerves in five groups, as above. (C) ChAT-positive nerves in five groups, as above. (D) Histograms of mean PGP9.5-positive nerve density in the SLGPs. (E) Graphs of mean TH-positive nerve density. (F) Histograms of mean ChAT-positive nerve density. Magnification of the objective lens: 20 ×. Scale bar = 100 μm. * <i>P</i> < 0.05 and ** <i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359157, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.g003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Measurement_of_nerve_density_by_immunohistochemical_analysis_/1359157", "title"=>"Measurement of nerve density by immunohistochemical analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992891"], "description"=>"<p>MiRNAs found to be significantly upregulated or downregulated in all tissues following A-TP compared with control samples were selected. (A) Heat map of miRNA profiles showing an increase or decrease in miRNA expression in the A-TP group. The coloring is standard; a red to green gradation in color represents higher to lower expression levels. The levels of miRNAs marked with red arrows were verified using quantitative assays. Detailed results of the levels of miRNAs in each layer of the hierarchical map are presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122674#pone.0122674.t002\" target=\"_blank\">Table 2</a>. (B)- (E) Expression levels of selected miRNAs identified by expression profiling were independently determined using qRT-PCR. qRT-PCR data were normalized to U6. ** <i>P</i> < 0.01 compared with control samples.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359153, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.g001", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MiRNA_expression_profiling_in_the_left_superior_FP_LSFP_subjected_to_atrial_tachypacing_A_TP_in_dogs_/1359153", "title"=>"MiRNA expression profiling in the left superior FP (LSFP) subjected to atrial tachypacing (A-TP) in dogs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992903"], "description"=>"<p>#Cfa-miRNA indicates the level of miRNA in canine model. DESeq statistical test was used to screen differentially expressed genes (<i>P</i> < 0.05)</p><p>Quantification of miRNA expression in A-TP group <i>vs</i>. Control group.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359165, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.t002", "stats"=>{"downloads"=>7, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantification_of_miRNA_expression_in_A_TP_group_vs_Control_group_/1359165", "title"=>"Quantification of miRNA expression in A-TP group <i>vs</i>. Control group.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992902"], "description"=>"<p>The Sequences of Primers of miRNAs.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359164, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Sequences_of_Primers_of_miRNAs_/1359164", "title"=>"The Sequences of Primers of miRNAs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992898"], "description"=>"<p>(A) Determination of ROS baseline levels of primary canine myocardial cells infected or not with lenti-miR-206. (B) To induce ROS, cells infected or not with lenti-anti-miR-206 exposed to 10 Gy of X-ray irradiation. Forty-eight hours after infection, the ROS levels were determined using the ROS-sensitive dye 2’,7’-dichlorofluorescein diacetate (DCF-DA). Fluorescent signals, reflecting the concentration of ROS, were measured by a fluorescence microscope under the same conditions. (C) Relative ROS levels in indicated groups of cells, as calculated by Image J analysis software (MD, USA). The normalized fluorescent signals of the cells infected with the control lentivirus were set as 100. (D) ROS levels were determined using DCF-DA in tissues. Dogs were injected with control lentivirus or the miR-206-overexpressing lentivirus. Two weeks after infection, the ROS levels in fresh tissues were measured. The level of DCF fluorescence was measured at 488 nm using a 96-well plate reader. **<i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359160, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_206_regulated_ROS_levels_in_vitro_and_in_vivo_/1359160", "title"=>"miR-206 regulated ROS levels <i>in vitro</i> and <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992896"], "description"=>"<p>(A) Putative miR-206-binding sequences in the 3’UTR of SOD1 mRNA, identified by RNAhybrid 2.2. (B) The predicted miR-206-SOD1 binding structure, identified by RNAhybrid 2.2. (C) Schematic diagram of constructed vectors. The 3’UTR region of SOD1 was cloned downstream of the luciferase reporter gene (pGL3-promoter vector). (D) The sequence of the luciferase vector in pGL3-SOD1-UTR-WT and pGL3-SOD1-UTR-Del. (E) Primary canine myocardial cells were transfected with <i>Firefly</i> luciferase expression vectors with pGL3-SOD1-UTR. Luciferase activity was assayed 24 h after transfection. The <i>Firefly</i> luciferase activity of each sample was normalized to <i>Renilla</i> luciferase activity. The normalized luciferase activity of the cells transfected with the control lentivirus was set as 100% relative luciferase activity. The column graphs show the means of at least three independent experiments performed in duplicate. (F) Tissues of the LSFPs were collected in each group. SOD1, and internal standard GAPDH protein levels were detected as above. Western blot bands were normalized to GAPDH. **<i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359158, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.g004", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SOD1_was_a_direct_target_of_miR_206_/1359158", "title"=>"SOD1 was a direct target of miR-206.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-27 04:14:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1992893"], "description"=>"<p>AF was induced by A-TP for 4 weeks. During each week of A-TP, a surface electrocardiogram (ECG) was recorded to determine the presence of AF by turning off the pacemaker. The atrial effective refractory period (AERP) was measured with S1-S2 programmed electrical stimulation, with S2 at coupling intervals starting at 150 ms and progressively shortened by 10 ms decrements and with a 2 × diastolic threshold. The longest S1-S2 coupling interval that failed to result in a propagated atrial response was taken as the local AERP. (A) The level of miR-206 in the lenti-control, lenti-miR-206, and lenti-anti-miR-206 groups two weeks after infection. (B) The AERP in control, A-TP, A-TP plus lenti-miR-206 and A-TP plus lenti-anti-miR-206 groups obtained in posterior wall of left atrium. (C) ECG of the sinus rhythm obtained. (D) ECG of AF obtained. * <i>P</i> < 0.05 and ** <i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["right atrial tachypacing", "ros", "Regulating SOD 1 BackgroundA", "rna", "Reactive oxygen species", "anr", "SOD 1", "mirna", "mir", "af", "superoxide dismutase 1", "AERP", "SLGP", "expression"], "article_id"=>1359155, "categories"=>["Biological Sciences"], "users"=>["Yujiao Zhang", "Shaohua Zheng", "Yangyang Geng", "Jiao Xue", "Zhongsu Wang", "Xinxing Xie", "Jiangrong Wang", "Shuyu Zhang", "Yinglong Hou"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122674.g002", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_atrial_fibrillation_AF_and_AERP_in_the_canine_model_/1359155", "title"=>"Characterization of atrial fibrillation (AF) and AERP in the canine model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-27 04:14:42"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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