The study investigates the role of cytosolic thioredoxin-1 in cardiac function and mitochondrial integrity using inducible, cell-specific gene deletion. Cardiomyocyte-specific loss of thioredoxin caused severe myocardial injury, ischemia, infarction and mitochondrial dysfunction. Endothelial-specific deletion impaired nitric oxide production. Recombinant human thioredoxin treatment improved mitochondrial structure and cardiac function in both models.
Cardiomyocyte-specific thioredoxin deletion caused severe myocardial ischemia, infarction, mitochondrial dysfunction and substantial mortality within three weeks. Endothelial deletion reduced nitric oxide production through eNOS dysfunction. Recombinant human thioredoxin restored mitochondrial structure, mitochondrial gene expression, OGG1 activity and cardiac function.
Txn^flox/flox conditional Knockout mouse, carrying a floxed cytosolic thioredoxin-1 allele for Cre-mediated deletion. The mice were crossed with tamoxifen-inducible αMHC-Cre for cardiomyocyte-specific deletion and VE-cadherin-CreERT2 for endothelial-specific deletion. These approaches enabled investigation of thioredoxin function in adult cardiac and vascular cells.
Cardiovascular disease, myocardial infarction, cardiac ischemia, mitochondrial dysfunction, oxidative stress, endothelial dysfunction, redox biology, cardioprotection
Txn conditional Knockout, Txn floxed allele, Cre-LoxP recombination, tamoxifen-inducible deletion, αMHC-Cre, VE-cadherin-CreERT2, cardiomyocyte-specific Knockout, endothelial-specific Knockout, mitochondrial functional analysis, recombinant thioredoxin rescue
De la conception du modèle aux résultats expérimentaux
Cité dans plus de 600 articles scientifiques
Collaboration avec 17 grands laboratoires pharmaceutiques,
plus de 170 entreprises biotechnologiques et plus de 380 établissements universitaires
Élaborées en collaboration avec des partenaires du secteur biopharmaceutique et en interne
et la garantie de la liberté d'exploitation
Modèles avec certificat sanitaire provenant d'éleveurs professionnels aux États-Unis et en Europe