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doi:10.22028/D291-41894
Titel: | Non-responsiveness to cardioprotection by ischaemic preconditioning in Ossabaw minipigs with genetic predisposition to, but without the phenotype of the metabolic syndrome |
VerfasserIn: | Kleinbongard, Petra Lieder, Helmut Raphael Skyschally, Andreas Alloosh, Mouhamad Gödecke, Axel Rahmann, Sven Sturek, Michael Heusch, Gerd |
Sprache: | Englisch |
Titel: | Basic Research in Cardiology |
Bandnummer: | 117 |
Heft: | 1 |
Verlag/Plattform: | Springer Nature |
Erscheinungsjahr: | 2022 |
Freie Schlagwörter: | Cardioprotection Genetic predisposition Ischaemic preconditioning Metabolic syndrome Myocardial ischaemia |
DDC-Sachgruppe: | 004 Informatik |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | The translation of successful preclinical and clinical proof-of-concept studies on cardioprotection to the beneft of patients with reperfused acute myocardial infarction has been difcult so far. This difculty has been attributed to confounders which patients with myocardial infarction typically have but experimental animals usually not have. The metabolic syndrome is a typical confounder. We hypothesised that there may also be a genuine non-responsiveness to cardioprotection and used Ossabaw minipigs which have the genetic predisposition to develop a diet-induced metabolic syndrome, but before they had developed the diseased phenotype. Using a prospective study design, a reperfused acute myocardial infarction was induced in 62 lean Ossabaw minipigs by 60 min coronary occlusion and 180 min reperfusion. Ischaemic preconditioning by 3 cycles of 5 min coronary occlusion and 10 min reperfusion was used as cardioprotective intervention. Ossabaw minipigs were stratifed for their single nucleotide polymorphism as homozygous for valine (V/V) or isoleucine (I/I)) in the γ-subunit of adenosine monophosphate-activated protein kinase. Endpoints were infarct size and area of no-refow. Infarct size (V/V: 54±8, I/I: 54±13% of area at risk, respectively) was not reduced by ischaemic preconditioning (V/V: 55±11, I/I: 46±11%) nor was the area of no-refow (V/V: 57±18, I/I: 49±21 vs. V/V: 57±21, I/I: 47±21% of infarct size). Bioinformatic comparison of the Ossabaw genome to that of Sus scrofa and Göttingen minipigs identifed diferences in clusters of genes encoding mitochondrial and infammatory proteins, including the janus kinase (JAK)—signal transducer and activator of transcription (STAT) pathway. The phosphorylation of STAT3 at early reperfusion was not increased by ischaemic preconditioning, different from the established STAT3 activation by cardioprotective interventions in other pig strains. Ossabaw pigs have not only the genetic predisposition to develop a metabolic syndrome but also are not amenable to cardioprotection by ischaemic preconditioning. |
DOI der Erstveröffentlichung: | 10.1007/s00395-022-00965-0 |
URL der Erstveröffentlichung: | https://doi.org/10.1007/s00395-022-00965-0 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-418949 hdl:20.500.11880/37479 http://dx.doi.org/10.22028/D291-41894 |
ISSN: | 1435-1803 0300-8428 |
Datum des Eintrags: | 15-Apr-2024 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Information |
In Beziehung stehendes Objekt: | https://static-content.springer.com/esm/art%3A10.1007%2Fs00395-022-00965-0/MediaObjects/395_2022_965_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1007%2Fs00395-022-00965-0/MediaObjects/395_2022_965_MOESM2_ESM.xlsx https://static-content.springer.com/esm/art%3A10.1007%2Fs00395-022-00965-0/MediaObjects/395_2022_965_MOESM3_ESM.xlsx |
Fakultät: | MI - Fakultät für Mathematik und Informatik |
Fachrichtung: | MI - Informatik |
Professur: | MI - Prof. Dr. Sven Rahmann |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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s00395-022-00965-0.pdf | 4,46 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons