Histone Deacetylase Inhibitor Treatment Increases Coronary t-PA Release in a Porcine Ischemia Model
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{"title"=>"Histone deacetylase inhibitor treatment increases coronary t-PA release in a porcine ischemia model", "type"=>"journal", "authors"=>[{"first_name"=>"Kristina", "last_name"=>"Svennerholm", "scopus_author_id"=>"56079326600"}, {"first_name"=>"Niklas", "last_name"=>"Bergh", "scopus_author_id"=>"36781595200"}, {"first_name"=>"Pia", "last_name"=>"Larsson", "scopus_author_id"=>"35553889900"}, {"first_name"=>"Sverker", "last_name"=>"Jern", "scopus_author_id"=>"7005751319"}, {"first_name"=>"Göran", "last_name"=>"Johansson", "scopus_author_id"=>"8903407200"}, {"first_name"=>"Björn", "last_name"=>"Biber", "scopus_author_id"=>"7004387881"}, {"first_name"=>"Michael", "last_name"=>"Haney", "scopus_author_id"=>"7006220929"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24818610", "sgr"=>"84901246309", "doi"=>"10.1371/journal.pone.0097260", "scopus"=>"2-s2.0-84901246309", "pui"=>"373143633", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"83162482-08c6-315c-b4ee-ecae19ce0ef8", "abstract"=>"BACKGROUND: The expression of the tissue plasminogen activator gene can be affected by histone deacetylation inhibition and thus appears to be under epigenetic control. OBJECTIVES: The study aimed to test if in vivo pharmacological intervention by valproic acid treatment would lead to increase in tissue plasminogen activator release capacity. METHODS: In an anaesthetized pig model, a controlled transient coronary occlusion was used to stimulate coronary tissue plasminogen activator release in a valproic acid treated (one week) and a non-treated group. Coronary venous blood samples from the ischemic region were collected, great cardiac vein thermodilution flow measurements were performed, and trans-coronary tissue plasminogen activator fluxes were calculated. Plasminogen activator inhibitor-1 was also measured. RESULTS: Adequate sampling from the affected area after the 10 minute ischemic period was confirmed by lactate measurements. Fluxes for tissue plasminogen activator at minutes 1, 3, 5, 7 and 10 were measured and then used to present cumulative net tissue plasminogen activator release for the whole measurement period for both groups. Area under the curve was higher for the valproic acid treated group at 10 minutes; 932 +/- 173 nanograms (n = 12) compared to the non-treated group, 451 +/- 78 nanograms (n = 10, p = 0.023). There was no difference in levels of plasminogen activator inhibitor-1 between groups. CONCLUSIONS: These findings support a proof of concept for histone deacetylation inhibition positive effect on tissue plasminogen activator expression in an in vivo setting. Further studies are needed to find an optimal way to implement histone deacetylation inhibition to achieve desired clinical changes in tissue plasminogen activator expression.", "link"=>"http://www.mendeley.com/research/histone-deacetylase-inhibitor-treatment-increases-coronary-tpa-release-porcine-ischemia-model", "reader_count"=>4, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>2, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>2, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1494037"], "description"=>"<p>Coronary t-PA fluxes are shown in Panel A for pre-ischemia (baseline), after 10 min of ischemia followed by 10 min of reperfusion for treated group (filled squares, n = 12) and for control group (open squares, n = 10). These are point measurements for observed t-PA fluxes at minutes 1, 3, 5, 7, and 10. One can note that there are different baselines for the two groups. The main result is derived from Panel A, and presented as the cumulative t-PA release over time in Panel B, as area under the curve (AUC). There is a clearly higher cumulative t-PA release for the VPA treated group (mixed between-within subjects ANOVA, p = 0.023); treated group (filled diamonds, n = 12) and control group (open diamonds, n = 10) data presented as mean ± SEM. There were also differences between groups (larger cumulative t-PA release in the treatment group) for specific measurements at minutes 10, 7, and 5 (t-test).</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cardiology", "Cardiovascular pharmacology", "Myocardial infarction", "hematology", "Blood coagulation", "Coagulation disorders"], "article_id"=>1023760, "categories"=>["Biological Sciences"], "users"=>["Kristina Svennerholm", "Niklas Bergh", "Pia Larsson", "Sverker Jern", "Göran Johansson", "Björn Biber", "Michael Haney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097260.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Coronary_t_PA_flux_/1023760", "title"=>"Coronary t-PA-flux.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-12 03:17:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1494035"], "description"=>"<p>Absolute t-PA concentrations in arterial blood are shown for pre-ischemia (baseline), as well as for the period after 10 min of ischemia and 10 min of reperfusion. Both the treated group (filled squares, n = 12) and the control group (open squares, n = 10) are shown. Data are presented as mean ± SEM. No differences were noted within groups over time, or between groups at any of the time intervals (mixed between-within subjects ANOVA). There was no sign here that the valproic acid treatment led to higher systemic blood levels of t-PA in the resting state. These results also showed that the coronary t-PA release did not affect systemic arterial t-PA levels.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cardiology", "Cardiovascular pharmacology", "Myocardial infarction", "hematology", "Blood coagulation", "Coagulation disorders"], "article_id"=>1023758, "categories"=>["Biological Sciences"], "users"=>["Kristina Svennerholm", "Niklas Bergh", "Pia Larsson", "Sverker Jern", "Göran Johansson", "Björn Biber", "Michael Haney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097260.g003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Arterial_t_PA_concentrations_/1023758", "title"=>"Arterial t-PA-concentrations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-12 03:17:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1494032"], "description"=>"<p>These are shown for pre-ischemia (baseline), after 10 min of ischemia followed by 10 min of reperfusion for treated group (filled squares, n = 12) and for control group (open squares, n = 10). Data are presented as mean ± SEM. Sampling of the ischemic area, as confirmed by positive lactate flux (regional myocardial lactate production in response to the local coronary occlusion), was observed in all animals (not shown individually) and is reflected by the immediate high positive lactate flux noted at reperfusion minute 1. This regional lactate flux was quickly ‘washed out’. No difference was found between groups (p = 0.853, mixed between-within subjects ANOVA).</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cardiology", "Cardiovascular pharmacology", "Myocardial infarction", "hematology", "Blood coagulation", "Coagulation disorders", "coronary"], "article_id"=>1023756, "categories"=>["Biological Sciences"], "users"=>["Kristina Svennerholm", "Niklas Bergh", "Pia Larsson", "Sverker Jern", "Göran Johansson", "Björn Biber", "Michael Haney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097260.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Absolute_values_of_coronary_lactate_fluxes_/1023756", "title"=>"Absolute values of coronary lactate-fluxes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-12 03:17:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1494038"], "description"=>"<p>HR =  heart rate (bpm); MAP =  mean arterial pressure (mm Hg); CSF  =  coronary sinus blood flow (mL/min). Control group (n = 10), treated group (n = 12). Data are presented as mean ± 95% SEM. * = p<0.05 using repeated measures ANOVA and when significant was followed by paired t test vs. baseline. A between-groups t test was performed, but no differences were found.</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cardiology", "Cardiovascular pharmacology", "Myocardial infarction", "hematology", "Blood coagulation", "Coagulation disorders"], "article_id"=>1023761, "categories"=>["Biological Sciences"], "users"=>["Kristina Svennerholm", "Niklas Bergh", "Pia Larsson", "Sverker Jern", "Göran Johansson", "Björn Biber", "Michael Haney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097260.t001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hemodynamic_results_/1023761", "title"=>"Hemodynamic results.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-12 03:17:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1494031"], "description"=>"<p>The left anterior descending artery and corresponding vein are depicted. A coronary snare is placed in the mid region of this artery, and when drawn, this generates a region of ischemia corresponding to a larger part of the anterior left ventricle. The coronary venous catheter is introduced through the right atrium, coronary sinus, and finally placed with the sampling tip in the proximal great cardiac vein, draining the left anterior descending vascular region (ischemic area).</p>", "links"=>[], "tags"=>["anatomy", "Cardiovascular anatomy", "cardiology", "Cardiovascular pharmacology", "Myocardial infarction", "hematology", "Blood coagulation", "Coagulation disorders", "vivo"], "article_id"=>1023754, "categories"=>["Biological Sciences"], "users"=>["Kristina Svennerholm", "Niklas Bergh", "Pia Larsson", "Sverker Jern", "Göran Johansson", "Björn Biber", "Michael Haney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097260.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_image_of_the_in_vivo_heart_preparation_/1023754", "title"=>"Schematic image of the in vivo heart preparation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-12 03:17:56"}

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