Selective Endothelial Overexpression of Arginase II Induces Endothelial Dysfunction and Hypertension and Enhances Atherosclerosis in Mice
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{"title"=>"Selective endothelial overexpression of arginase ii induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Boris L.", "last_name"=>"Vaisman", "scopus_author_id"=>"7003495938"}, {"first_name"=>"Karen L.", "last_name"=>"Andrews", "scopus_author_id"=>"7102643234"}, {"first_name"=>"Sacha M.L.", "last_name"=>"Khong", "scopus_author_id"=>"32167538700"}, {"first_name"=>"Katherine C.", "last_name"=>"Wood", "scopus_author_id"=>"10139883500"}, {"first_name"=>"Xiao L.", "last_name"=>"Moore", "scopus_author_id"=>"6508107548"}, {"first_name"=>"Yi", "last_name"=>"Fu", "scopus_author_id"=>"55712879800"}, {"first_name"=>"Diane M.", "last_name"=>"Kepka-Lenhart", "scopus_author_id"=>"6602244138"}, {"first_name"=>"Sidney M.", "last_name"=>"Morris", "scopus_author_id"=>"56349390400"}, {"first_name"=>"Alan T.", "last_name"=>"Remaley", "scopus_author_id"=>"7006511029"}, {"first_name"=>"Jaye P.F.", "last_name"=>"Chin-Dusting", "scopus_author_id"=>"7004199219"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"365285023", "sgr"=>"84864050457", "pmid"=>"22829869", "scopus"=>"2-s2.0-84864050457", "doi"=>"10.1371/journal.pone.0039487"}, "id"=>"d2636b43-df88-371e-9a8e-a0a1fa015317", "abstract"=>"BACKGROUND: Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO) bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII) gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions.\\n\\nCONCLUSION: We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.", "link"=>"http://www.mendeley.com/research/selective-endothelial-overexpression-arginase-ii-induces-endothelial-dysfunction-hypertension-enhanc", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Master"=>7, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Master"=>7, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>11, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/606432"], "description"=>"<p>Expression analysis of <b>B</b> eNOS and <b>C</b> iNOS using real-time quantitative RT-PCR and protein expression of <b>D</b> eNOS and <b>E</b> iNOS and <b>F</b> eNOS monomer:dimer ratio in aorta from male homozygous Line 11 hArgII mice and their WT littermate controls. Data are presented as mean ± SEM; n = 4−8. Values were compared with an unpaired Student’s t-test where * = P<0.05.</p>", "links"=>[], "tags"=>["blot", "arginase", "ii", "aorta", "homozygous", "11", "hargii", "mice", "wt", "littermate"], "article_id"=>276900, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_western_blot_analysis_of_arginase_II_in_A_kidney_heart_and_aorta_of_male_homozygous_Line_11_hArgII_mice_TG_and_their_WT_littermate_controls_/276900", "title"=>"Representative western blot analysis of arginase II in A kidney, heart and aorta of male homozygous Line 11 hArgII mice (TG) and their WT littermate controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 02:13:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/606553"], "description"=>"<p>Macrophage activities are mean and range for two groups each of pooled samples for male and female homozygous hArgII mice and littermate controls (n = 4/group for WT; n = 4 or 5/group for hArgII lines 11 and 4, respectively). Arginase activity in extracts from lung endothelial cells immunomagnetically separated to endothelial cells (EC fraction) or fractions depleted of endothelial cells (EC depleted) from <b>C</b> C57Bl/6 (n = 4) and <b>D</b> from hArgII Line 4 mice (n = 4). Data are presented as mean ± SEM. Values were compared <b>A</b> with a 1-way ANOVA with Bonferroni posthoc test and <b>B</b>–<b>D</b> with Student’s t-test where *  =  P<0.05, **  =  P<0.01 and ***  =  P<0.001.</p>", "links"=>[], "tags"=>["activities", "heterozygous", "hargii", "11", "mice", "males", "peritoneal"], "article_id"=>277030, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Arginase_activities_of_A_heterozygous_hArgII_Line_4_and_Line_11_mice_and_C57Bl_6_males_n_8202_8202_3_8722_5_and_B_resident_peritoneal_macrophages_/277030", "title"=>"Arginase activities of: A heterozygous hArgII Line 4 and Line 11 mice and C57Bl/6 males (n = 3−5) and B resident peritoneal macrophages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 02:14:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/606681"], "description"=>"<p><b>D</b> NO production as determined by measuring NOx (nitrate and nitrate) using the Griess reaction in homogenized aorta and normalized to protein concentration in aorta from homozygous hArgII line 11 males and littermate non-transgenic control males (n = 8−9). Data are presented as mean ± SEM. EC<sub>50</sub> and E<sub>max</sub> values were compared using 1-way ANOVA with Bonferroni posthoc test, where * =  P<0.05 and *** =  P<0.001.</p>", "links"=>[], "tags"=>["curves", "endothelium-dependent", "vasodilator", "acetylcholine", "nitric", "oxide", "synthase", "inhibitor", "ng-nitro-l-arginine", "methyl", "ester", "100", "aorta", "constricted", "cirazoline", "mesenteric", "arteries", "potassium", "homozygous", "hargii", "11", "mice", "wt", "littermate", "controls"], "article_id"=>277123, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Concentration_response_curves_to_the_endothelium_dependent_vasodilator_acetylcholine_ACh_before_and_after_the_addition_of_the_nitric_oxide_synthase_inhibitor_NG_nitro_L_arginine_methyl_ester_NAME_100_181_mol_L_in_A_aorta_constricted_with_cirazoline_and_m/277123", "title"=>"Concentration response curves to the endothelium-dependent vasodilator acetylcholine (ACh) before and after the addition of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (NAME; 100 µmol/L) in A aorta constricted with cirazoline and mesenteric arteries constricted with B cirazoline or C high potassium from male homozygous hArgII Line 11 mice (n = 4−6) and their WT littermate controls (WT; n = 5−6).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 02:15:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/606764"], "description"=>"<p>The box extends 25<sup>th</sup> percentile to the 75<sup>th</sup> percentile with the median represented by the line within the box. Measurements were from control non-transgenic sibling males (n = 9) versus Line 4 and 11 hArgII males (n = 9). Values were compared using unpaired Student’s t-tests where *  =  P<0.05 and **P <i> = </i> <0.01.</p>", "links"=>[], "tags"=>["anaesthetized", "hargii", "non-transgenic", "mice", "presented", "plots", "systolic", "arterial", "diastolic"], "article_id"=>277237, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blood_pressure_of_anaesthetized_hArgII_and_non_transgenic_mice_presented_as_box_plots_of_A_systolic_blood_pressure_systolic_BP_B_mean_arterial_pressure_MAP_and_C_diastolic_BP_/277237", "title"=>"Blood pressure of anaesthetized hArgII and non-transgenic mice presented as box plots of A systolic blood pressure (systolic BP), B mean arterial pressure (MAP) and C diastolic BP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 02:15:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/606881"], "description"=>"<p>C Plaque lesion area in aorta from 8-month-old female ApoE −/−sibling control (n = 22) and heterozygous Line 4 hArgII x ApoE −/− females (n = 11) and heterozygous and homozygous Line 11 hArgII x ApoE −/− females (n = 12). Images of en face Sudan IV staining of atherosclerotic plaque in the whole aorta from 8-month-old <b>D</b> heterozygous Line 4 female hArgII x ApoE −/− and E ApoE −/− sibling control mouse. Data are presented as mean ± SEM. Values were compared with either a unpaired Student’s t-test or a 1-way ANOVA with Bonferroni posthoc test where *  =  P<0.05 and **  =  P<0.01.</p>", "links"=>[], "tags"=>["lipid", "profiles", "triglycerides", "phospholipids", "cholesteryl", "esters", "lipoprotein", "8-month-old", "apoe", "heterozygous", "homozygous", "hargii", "mice", "11"], "article_id"=>277339, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_lipid_profiles_including_total_cholesterol_TC_triglycerides_TG_phospholipids_PL_free_cholesterol_FC_cholesteryl_esters_CE_and_high_density_lipoprotein_cholesterol_HDL_C_for_female_8_month_old_A_ApoE_8722_8722_sibling_control_n_8202_8202_21_and_het/277339", "title"=>"Plasma lipid profiles including total cholesterol (TC), triglycerides (TG), phospholipids (PL), free cholesterol (FC), cholesteryl esters (CE) and high density lipoprotein cholesterol (HDL-C) for female 8-month-old A ApoE −/− sibling control (n = 21) and heterozygous and homozygous Line 4 hArgII x ApoE −/− mice (n = 9) or B ApoE −/− sibling control (n = 21) and heterozygous and homozygous Line 11 hArgII x ApoE −/− mice (n = 19).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 02:16:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/606959"], "description"=>"<p>Expression of hArgII, mArgI and mArgII in five tissues (aorta, heart, kidney, liver and lung) of heterozygous Line 4 hArgII mice (n = 3) and C57Bl/6NTac (n = 3). All data were presented as percent relative to expression of mArgII in normal kidney, which was assigned as 100%. Values are given as mean ± SEM and compared using Student’s t-test where NS represents not significant.</p>", "links"=>[], "tags"=>["margi", "margii", "mrnas", "tissues", "hargii", "transgenic"], "article_id"=>277434, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_hArgII_mArgI_and_mArgII_mRNAs_in_tissues_of_female_C57Bl_6NT_and_hArgII_transgenic_mice_/277434", "title"=>"Expression of hArgII, mArgI and mArgII mRNAs in tissues of female C57Bl/6NT and hArgII transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 02:16:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/607006"], "description"=>"<p>EC<sub>5O</sub> values are expressed as –log M, E<sub>max</sub> values as the maximum response to NA in g, R<sub>max</sub> values as % reversal of the level of pre-contraction in response to 10 µM of the SNP. Values are given as mean ± SEM. n = 4−8 per group.</p>*<p><i>P<</i>0.05,</p>**<p><i>P<</i>0.01,</p>***<p><i>P<</i>0.001 vs WT control (Student’s t-test).</p>", "links"=>[], "tags"=>["noradrenaline", "nitroprusside", "nos", "inhibitor", "l-name", "aorta", "mesenteric", "arteries", "homozygous", "11", "hargii", "mice", "wt", "littermate"], "article_id"=>277475, "categories"=>["Physiology", "Biotechnology", "Cell Biology"], "users"=>["Boris L. Vaisman", "Karen L. Andrews", "Sacha M. L. Khong", "Katherine C. Wood", "Xiao L. Moore", "Yi Fu", "Diane M. Kepka-Lenhart", "Sidney M. Morris Jr", "Alan T. Remaley", "Jaye P. F. Chin-Dusting"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039487.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Responses_to_noradrenaline_NA_and_sodium_nitroprusside_SNP_in_the_absence_and_presence_of_the_NOS_inhibitor_L_NAME_100_181_M_in_aorta_and_small_mesenteric_arteries_from_male_homozygous_Line_11_hArgII_mice_and_their_male_WT_littermate_controls_/277475", "title"=>"Responses to noradrenaline (NA) and sodium nitroprusside (SNP) in the absence and presence of the NOS inhibitor L-NAME (100 µM) in aorta and small mesenteric arteries from male homozygous Line 11 hArgII mice and their male WT littermate controls.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 02:17:15"}

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Relative Metric

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