Renalase Deficiency in Heart Failure Model of Rats—A Potential Mechanism Underlying Circulating Norepinephrine Accumulation
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{"title"=>"Renalase deficiency in heart failure model of rats-A potential mechanism underlying circulating norepinephrine accumulation", "type"=>"journal", "authors"=>[{"first_name"=>"Rong", "last_name"=>"Gu", "scopus_author_id"=>"55651087400"}, {"first_name"=>"Wen", "last_name"=>"Lu", "scopus_author_id"=>"55484293300"}, {"first_name"=>"Jun", "last_name"=>"Xie", "scopus_author_id"=>"57043834600"}, {"first_name"=>"Jian", "last_name"=>"Bai", "scopus_author_id"=>"37107211800"}, {"first_name"=>"Biao", "last_name"=>"Xu", "scopus_author_id"=>"35085585600"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"21297953", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0014633", "issn"=>"19326203", "scopus"=>"2-s2.0-79551621412", "pui"=>"361218314", "sgr"=>"79551621412"}, "id"=>"c1dbbc43-a269-3430-abf8-04e8bbfa1aef", "abstract"=>"BACKGROUND: Sympathetic overactivity and catecholamine accumulation are important characteristic findings in heart failure, which contribute to its pathophysiology. Here, we identify a potential mechanism underlying norepinephrine accumulation in a rat model of heart failure.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Initially, we constructed a rat model of unilateral renal artery stenosis (n = 16) and found that the expression of renalase, a previously identified secreted amine oxidase, was markedly reduced in the ischemic compared to the non-ischemic kidney (protein: 0.295±0.085 versus 0.765±0.171, p<0.05). Subsequently, we utilized an isolated perfused rat kidney model to demonstrate that the clearance rate of norepinephrine decreased with reduction of perfusion flow. On the basis of these findings, we hypothesized the reduced renal blood supply which occurs in heart failure would result in impaired synthesis of renalase by the kidney and consequently reduced degradation of circulating norepinephrine. To verify this, we used a rat model of infarction-induced heart failure (n = 12 per group). In these rats, the flow velocity of renal artery, when measured at four weeks, is obviously lower in the operation group. Renal expression of renalase was reduced (protein: 0.476±0.043 for control, 0.248±0.029 for operation versus 0.636±0.151 for sham-operation) and this was associated with an increase in circulating norepinephrine (0.168±0.016 ng/mL for control, 0.203±0.019 ng/mL for operation versus 0.138±0.008 ng/mL for sham-operation).\\n\\nCONCLUSIONS/SIGNIFICANCE: Renalase expression is influenced by renal blood flow and impaired synthesis of renalase by the kidney may represent a potential mechanism underlying circulating norepinephrine accumulation in heart failure.", "link"=>"http://www.mendeley.com/research/renalase-deficiency-heart-failure-model-ratsa-potential-mechanism-underlying-circulating-norepinephr", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>6, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "reader_count_by_country"=>{"Canada"=>1, "United Kingdom"=>1, "India"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/801126"], "description"=>"<p>A, There is no statistic difference between renalase expression between the ACEI and control groups both in the ischemia kidney and the nonischemia one. B, Western blotting showing renalase protein expression of ischemia kidney is lower than that of the nonischemia one. Alpha-tubulin also shown as a housekeeping control. Corresponding graph shows accumulated results from n = 8 (A) or n = 16 (B) for each group (0.295±0.085 versus 0.765±0.171). *<i>p</i><0.01 vs. ischemic kidney. NS: No statistical difference is existed between the two groups.</p>", "links"=>[], "tags"=>["renalase", "diminished", "ischemic", "compared", "non-ischemic"], "article_id"=>471491, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_expression_of_renalase_diminished_in_the_ischemic_compared_to_the_non_ischemic_kidney_/471491", "title"=>"Protein expression of renalase diminished in the ischemic compared to the non-ischemic kidney.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:24:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/801419"], "description"=>"<p>Western blot showing expression of renalase at different time points (24 h–4 weeks) post-LAD ligation. Alpha-tubulin expression is also shown as a housekeeping control. Corresponding graph shows accumulated results from n = 4 for each time point (1.223±0.086 for 24h, 1.556±0.102 for 1w, 0.987±0.056 for 2w, 1.112±0.057 for 3w, 0.945±0.078 for 4w). * <i>p</i><0.05 vs. 24h, 2w, 3w and 4w. ** <i>p</i><0.05 vs. 24h.</p>", "links"=>[], "tags"=>["kidney", "increases", "subsequently", "decreases", "progression", "post-lad"], "article_id"=>471784, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Renalase_expression_in_the_kidney_increases_and_subsequently_decreases_with_progression_of_heart_failure_post_LAD_ligation_/471784", "title"=>"Renalase expression in the kidney increases and subsequently decreases with progression of heart failure post-LAD ligation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:29:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/801257"], "description"=>"<p><b>A</b>, Ultrasonic image<b>s</b> of renal artery flow velocity of different groups. <b>B</b>, Corresponding graph shows accumulated results of flow velocity from n = 12 for each group (21.93±2.40 cm/s for control, 12.43±0.82 cm/s for operation versus 20.35±1.76 cm/s for sham-operation). *<i>p</i><0.05 vs. sham-operation, <i>p</i><0.05 vs. control.</p>", "links"=>[], "tags"=>["velocity", "renal", "artery"], "article_id"=>471630, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_flow_velocity_of_renal_artery_is_obviously_lower_in_the_operation_group_of_heart_failure_model_/471630", "title"=>"The flow velocity of renal artery is obviously lower in the operation group of heart failure model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:27:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/801723"], "description"=>"<p>*<i>p</i><0.05 vs. operation,</p><p>**<i>p</i><0.01 vs. operation.</p>", "links"=>[], "tags"=>["characteristics", "cardiac", "rats", "weeks", "post-lad"], "article_id"=>472089, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.t001", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physical_characteristics_and_cardiac_function_evaluation_of_rats_4_weeks_post_LAD_ligation_/472089", "title"=>"Physical characteristics and cardiac function evaluation of rats 4 weeks post-LAD ligation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-01-31 00:34:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/801334"], "description"=>"<p>Alpha-tubulin also shown as a housekeeping control. Corresponding graph shows accumulated results from n = 12 for each group (0.476±0.043 for control, 0.248±0.029 for operation versus 0.636±0.151 for sham-operation). *<i>p</i><0.01 vs. sham-operation, <i>p</i><0.01 vs. control.</p>", "links"=>[], "tags"=>["renalase", "kidneys", "rats", "weeks", "lad"], "article_id"=>471702, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_expression_of_renalase_is_decreased_in_kidneys_from_heart_failure_rats_four_weeks_after_LAD_ligation_/471702", "title"=>"Protein expression of renalase is decreased in kidneys from heart failure rats four weeks after LAD ligation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:28:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/801204"], "description"=>"<p><b>A</b>, Concentration of norepinephrine at different time points in the perfusion medium, using a perfusion flow rate of 10 mL/min. <b>B</b>, Clearance rate of norepinephrine at conditions of different perfusion flow. In the hypoperfusion group, the perfusion flow rate is 10 mL/min for the initial 30 min, followed by 5 mL/min for the succeeding 60 min. In the control group, the perfusion flow rate is constant at 10 mL/min for 90 min. *<i>P</i><0.01 vs. control. <b>C</b>, Dose-response curve analysis (renal flow/norepinephrine clearance) in isolated perfused rat kidney model. The norepinephrine clearance is increased with increment in perfusion flow below 10mL/min while the clearance remained stable at 15mL/min as compared with 10mL/min. <b>D</b>, Renalase activity and concentration in the perfusate at different time points during the perfusion. The activity and concentration are undetectable at time 0. But within 10 minutes of the initiation of norepinephrine perfusion, renalase activity and concentration increased significantly and remained high after 20 minutes during the perfusion procedure. n = 5 per group.</p>", "links"=>[], "tags"=>["clearance", "hypoperfused"], "article_id"=>471575, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Norepinephrine_clearance_is_decreased_in_the_hypoperfused_kidney_/471575", "title"=>"Norepinephrine clearance is decreased in the hypoperfused kidney.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:26:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/801494"], "description"=>"<p><b>A</b>, Plasma norepinephrine concentration in different groups (0.168±0.016 ng/mL for control, 0.203±0.019 ng/mL for operation versus 0.138±0.008 ng/mL for sham-operation). <b>B</b>, Plasma renalase concentration in different groups (0.535±0.109 ug/mL for control, 1.144±0.243 ug/mL for operation versus 0.872±0.171 ug/mL for sham-operation). n = 12 per group. *<i>p</i><0.05.</p>", "links"=>[], "tags"=>["norepinephrine", "renalase", "concentrations"], "article_id"=>471865, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g006", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_norepinephrine_and_renalase_concentrations_are_both_increased_in_heart_failure_rats_/471865", "title"=>"Plasma norepinephrine and renalase concentrations are both increased in heart failure rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:31:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/400659"], "description"=>"<div><h3>Background</h3><p>Sympathetic overactivity and catecholamine accumulation are important characteristic findings in heart failure, which contribute to its pathophysiology. Here, we identify a potential mechanism underlying norepinephrine accumulation in a rat model of heart failure.</p><h3>Methodology/Principal Findings</h3><p>Initially, we constructed a rat model of unilateral renal artery stenosis (n = 16) and found that the expression of renalase, a previously identified secreted amine oxidase, was markedly reduced in the ischemic compared to the non-ischemic kidney (protein: 0.295±0.085 versus 0.765±0.171, <em>p</em><0.05). Subsequently, we utilized an isolated perfused rat kidney model to demonstrate that the clearance rate of norepinephrine decreased with reduction of perfusion flow. On the basis of these findings, we hypothesized the reduced renal blood supply which occurs in heart failure would result in impaired synthesis of renalase by the kidney and consequently reduced degradation of circulating norepinephrine. To verify this, we used a rat model of infarction-induced heart failure (n = 12 per group). In these rats, the flow velocity of renal artery, when measured at four weeks, is obviously lower in the operation group. Renal expression of renalase was reduced (protein: 0.476±0.043 for control, 0.248±0.029 for operation versus 0.636±0.151 for sham-operation) and this was associated with an increase in circulating norepinephrine (0.168±0.016 ng/mL for control, 0.203±0.019 ng/mL for operation versus 0.138±0.008 ng/mL for sham-operation).</p><h3>Conclusions/Significance</h3><p>Renalase expression is influenced by renal blood flow and impaired synthesis of renalase by the kidney may represent a potential mechanism underlying circulating norepinephrine accumulation in heart failure.</p></div>", "links"=>[], "tags"=>["renalase", "deficiency", "circulating", "norepinephrine", "accumulation"], "article_id"=>139131, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633", "stats"=>{"downloads"=>36, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Renalase_Deficiency_in_Heart_Failure_Model_of_Rats_A_Potential_Mechanism_Underlying_Circulating_Norepinephrine_Accumulation/139131", "title"=>"Renalase Deficiency in Heart Failure Model of Rats—A Potential Mechanism Underlying Circulating Norepinephrine Accumulation", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-01-31 02:32:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/801596"], "description"=>"<p>Renalase expression is demonstrated immunohistochemically in kidney cortex (<b>A–C</b>) and medulla (<b>D–F</b>). <b>A</b>, <b>D</b>, Control. <b>B</b>, <b>E</b>, Operation. <b>C</b>, <b>F</b>, Sham-operation. <b>G–H</b>, Quantification of renalase expression in different groups in renal cortex (<b>G</b>) and medulla (<b>H</b>). n = 12 per group. *<i>p</i><0.01. Scale bars: 100 µm(A–F).</p>", "links"=>[], "tags"=>["reduced", "kidneys"], "article_id"=>471965, "categories"=>["Medicine", "Cancer"], "users"=>["Rong Gu", "Wen Lu", "Jun Xie", "Jian Bai", "Biao Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014633.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Renalase_expression_is_reduced_in_the_kidneys_of_heart_failure_rats_/471965", "title"=>"Renalase expression is reduced in the kidneys of heart failure rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-31 00:32:45"}

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Relative Metric

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