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Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice
by Simon F. De Meyer, Alexander S. Savchenko, Michael S. Haas, Daphne Schatzberg, Michael C. Carroll, Alexandra Schiviz, Barbara Dietrich, Hanspeter Rottensteiner, Friedrich Scheiflinger, and Denisa D. Wagner Blood Volume 120(26): December 20, 2012 ©2012 by American Society of Hematology
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Infarct volumes after transient LAD occlusion in WT mice, Adamts13−/− mice and WT mice treated with rhADATMS13. Infarct volumes after transient LAD occlusion in WT mice, Adamts13−/− mice and WT mice treated with rhADATMS13. Top: Representative TTC stains of transverse sections of the left ventricle (LV) of the 3 groups after 1 hour of LAD occlusion followed by 23 hours of reperfusion. Infarctions appear as white. Bottom: Myocardial infarctions (expressed as percentage of the LV) of the 3 groups as measured by planimetry at day 1 after LAD occlusion (*P < .05 compared with the WT group). Simon F. De Meyer et al. Blood 2012;120: ©2012 by American Society of Hematology
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Troponin-I levels after transient LAD occlusion are decreased in mice treated with rhADAMTS13.
Troponin-I levels after transient LAD occlusion are decreased in mice treated with rhADAMTS13. After 1 hour of LAD occlusion followed by 23 hours of reperfusion, plasma was collected from WT mice and WT mice treated with rhADAMTS13. In these plasma samples, troponin-I levels were determined as measure for cardiac injury (*P < .05). Simon F. De Meyer et al. Blood 2012;120: ©2012 by American Society of Hematology
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rhADAMTS13 reduces myocardial apoptosis after transient LAD occlusion.
rhADAMTS13 reduces myocardial apoptosis after transient LAD occlusion. (A) Representative immunofluorescent DAPI (blue), TUNEL (green), and Gr-1 (red) stainings of sections from the ischemic area in the hearts of mice that received rADAMTS13 or vehicle. Apoptosis was absent in nonischemic areas (not shown). The higher magnification of the double stain (Gr-1/TUNEL) shows that majority of TUNEL-positive cells are not Gr-1–positive, that is, they are green rather than yellow (arrows). (B) The apoptotic index of both groups was determined by calculating the percentage of apoptotic cells (measured in 3 different view fields per section, 4 sections per mouse with 3 mice per group, ***P < .001). Scale bar = 50 μm. Simon F. De Meyer et al. Blood 2012;120: ©2012 by American Society of Hematology
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Treatment with rhADAMTS13 reduces neutrophil infiltration and affects microthrombi events during myocardial ischemia/ reperfusion injury. Treatment with rhADAMTS13 reduces neutrophil infiltration and affects microthrombi events during myocardial ischemia/ reperfusion injury. After 1 hour of LAD occlusion and 23 hours of reperfusion, hearts from mice treated with either vehicle or rhADAMTS13 were harvested and sectioned for immunohistochemical analysis. (A) CD41 staining of heart sections. Adherent platelets, positive for CD41 (brown arrows), were seen only in some vessels and were detected only in vehicle, but not in rhADAMTS13-treated mice. Bottom: negative control staining without a primary antibody. (B) Gr-1–expressing neutrophils (brown color) infiltrated ischemic myocardium of vehicle-treated mice but significantly less did so in rhADAMTS13-treated mice. Bottom: Gr-1–positive cells in the ischemic area were counted in 5 different fields of view per section and numbers were expressed as positive cells per 1 mm2 of infracted area (3 mice per group, **P < .01). Scale bar = 100 μm. Simon F. De Meyer et al. Blood 2012;120: ©2012 by American Society of Hematology
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