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Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia/reperfusion injury.
Heger, Jacqueline; Hirschhäuser, Christine; Bornbaum, Julia; Sydykov, Akylbek; Dempfle, Astrid; Schneider, André; Braun, Thomas; Schlüter, Klaus-Dieter; Schulz, Rainer.
Afiliação
  • Heger J; Justus-Liebig-University Giessen, Physiologisches Institut, Giessen, Germany. Electronic address: Jacqueline.Heger@physiologie.med.uni-giessen.de.
  • Hirschhäuser C; Justus-Liebig-University Giessen, Physiologisches Institut, Giessen, Germany.
  • Bornbaum J; Justus-Liebig-University Giessen, Physiologisches Institut, Giessen, Germany.
  • Sydykov A; Justus-Liebig-University Giessen, Excellence Cluster Cardio-Pulmonary System (ECCPS), Giessen, Germany.
  • Dempfle A; Universitätsklinikum Schleswig-Holstein, Christian-Albrechts-University Kiel, Institute for Medical Informatics and Statistics, Kiel, Germany.
  • Schneider A; Max-Planck-Institute for Heart and Lung Research (MPI), Bad Nauheim, Germany.
  • Braun T; Max-Planck-Institute for Heart and Lung Research (MPI), Bad Nauheim, Germany.
  • Schlüter KD; Justus-Liebig-University Giessen, Physiologisches Institut, Giessen, Germany.
  • Schulz R; Justus-Liebig-University Giessen, Physiologisches Institut, Giessen, Germany.
Free Radic Biol Med ; 165: 14-23, 2021 03.
Article em En | MEDLINE | ID: mdl-33476795
Monoamine oxidase B (MAO-B), a protein localized at the outer mitochondrial membrane, catalyzes the oxidative deamination of biogenic amines thereby producing reactive oxygen species (ROS). Increased ROS formation contributes to myocardial ischemia/reperfusion (I/R); however, the importance of different ROS producing enzymes for increased I/R-induced ROS formation and the subsequent I/R injury is still a matter of debate. Here we describe the first cardiomyocytes-specific MAO-B knockout mouse and test the hypothesis that lack of cardiomyocyte MAO-B protects the heart from I/R injury. A cardiac-specific and tamoxifen-inducible MAO-B knockout mouse (MAO-B KO) was generated using the Cre/lox system; Cre-negative MAO-Bfl/fl littermates served as controls (WT). Lack of MAO-B was verified by Western blot and immunohistochemistry. Cardiac function of MAO-B KO and WT was analyzed by echocardiography, quantification of mitochondrial ROS production, and measurement of myocardial infarct size (in % of ventricle) in hearts exposed to global I/R using the Langendorff technique. MAO-B protein expression was significantly down-regulated in MAO-B KO mice after two weeks of tamoxifen feeding followed by ten weeks of feeding with normal chow. ROS formation stimulated by the MAO-B-specific substrate ß-phenylethylamin (PEA; 250 µM) was significantly lower in mitochondria isolated from MAO-B KO compared to WT hearts (WT 4.5 ± 0.8 a. u.; MAO-B KO 1.2 ± 0.3 a. u.). Echocardiography revealed no significant differences in LV dimensions as well as ejection fraction (EF) between WT and MAO-B KO mice (EF: WT 67.3 ± 8.8%; MAO-B KO 67.7 ± 6.5%). After I/R, infarct size was significantly lower in MAO-B KO hearts (WT 69.3 ± 15.1%; MAO-B KO 46.8 ± 12.0%). CONCLUSION: Lack of cardiomyocytes-specific MAO-B reduces infarct size suggesting that MAO-B activity contributes to acute reperfusion injury.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão Miocárdica Limite: Animals Idioma: En Revista: Free Radic Biol Med Assunto da revista: BIOQUIMICA / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão Miocárdica Limite: Animals Idioma: En Revista: Free Radic Biol Med Assunto da revista: BIOQUIMICA / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de publicação: Estados Unidos