Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen: 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 GrößeFormat 
s00395-022-00965-0.pdf4,46 MBAdobe PDFÖffnen/Anzeigen


Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons