Cardiomyocyte-specific deletion of thioredoxin promotes myocardial injury, infarction and mitochondrial dysfunction: translocation of cytosolic thioredoxin into mitochondria rescue myocardial dysfunction by restoration of cardiac mitochondrial structure and function.
- 1Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, Texas, 79430, USA.
- 2Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, Texas, 79430, USA. Electronic address: [email protected].
Abstract
Cytosolic thioredoxin is a protein disulfide reductase that is involved in several redox-related functions within cells. However, the specific role of Trx in cardiomyocytes or endothelial cells in the normal heart remains unclear. We created a Trx-floxed mouse strain (Trx fl/fl) to specifically understand whether deletion of Trx in cardiomyocytes or endothelial cell would have specific detrimental myocardial effects. We show that specific deletion of Trx in cardiomyocytes of adult mice (Trxfl/fl;αMHC-Cre(Tam)) caused severe ischemia and infarction along with heart mitochondrial dysfunction and significant mortality within 3 weeks. In contrast, mice with deletion of Trx in the endothelial cells (Trx;fl/fl;VECad-CreERT2(Tam)) survived with significant decrease in nitric oxide (NO) production due to dysfunction of nitric oxide synthase (eNOS). In rescue experiments, Trxfl/fl;αMHC-Cre(Tam) or Trx;fl/fl;VECad-CreERT2(Tam) mice treated with human recombinant thioredoxin (rhTrx) rescued altered mitochondrial structure and function with improved heart function. Further, rhTrx restored the expression of mitochondrial genes and proteins and Ogg1 activity. Taken together, our study demonstrates a critical role of Trx within the cardiac mitochondria and endothelial cells that rescue myocardial dysfunction due to deletion of Trx in cardiomyocytes as well as endothelial cell by rescue of mitochondrial structure, function, and improving eNOS function within the heart.
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BibTeX
@article{kumar2026cardiomyocytespecific,
title = {{Cardiomyocyte-specific deletion of thioredoxin promotes myocardial injury, infarction and mitochondrial dysfunction: translocation of cytosolic thioredoxin into mitochondria rescue myocardial dysfunction by restoration of cardiac mitochondrial structure and function.}},
author = {Sudhir Kumar and Richa Rani and Venkatesh Sridharan and Scott Shurmur and Kumuda C Das},
journal = {Redox biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104435},
url = {https://europepmc.org/article/MED/42868635},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Cardiomyocyte-specific deletion of thioredoxin promotes myocardial injury, infarction and mitochondrial dysfunction: translocation of cytosolic thioredoxin into mitochondria rescue myocardial dysfunction by restoration of cardiac mitochondrial structure and function.
AU - Sudhir Kumar
AU - Richa Rani
AU - Venkatesh Sridharan
AU - Scott Shurmur
AU - Kumuda C Das
PY - 2026
DA - 2026/10/10
JO - Redox biology
DO - 10.1016/j.redox.2026.104435
UR - https://europepmc.org/article/MED/42868635
AB - Cytosolic thioredoxin is a protein disulfide reductase that is involved in several redox-related functions within cells. However, the specific role of Trx in cardiomyocytes or endothelial cells in the normal heart remains unclear. We created a Trx-floxed mouse strain (Trx fl/fl) to specifically understand whether deletion of Trx in cardiomyocytes or endothelial cell would have specific detrimental myocardial effects. We show that specific deletion of Trx in cardiomyocytes of adult mice (Trxfl/fl;αMHC-Cre(Tam)) caused severe ischemia and infarction along with heart mitochondrial dysfunction and significant mortality within 3 weeks. In contrast, mice with deletion of Trx in the endothelial cells (Trx;fl/fl;VECad-CreERT2(Tam)) survived with significant decrease in nitric oxide (NO) production due to dysfunction of nitric oxide synthase (eNOS). In rescue experiments, Trxfl/fl;αMHC-Cre(Tam) or Trx;fl/fl;VECad-CreERT2(Tam) mice treated with human recombinant thioredoxin (rhTrx) rescued altered mitochondrial structure and function with improved heart function. Further, rhTrx restored the expression of mitochondrial genes and proteins and Ogg1 activity. Taken together, our study demonstrates a critical role of Trx within the cardiac mitochondria and endothelial cells that rescue myocardial dysfunction due to deletion of Trx in cardiomyocytes as well as endothelial cell by rescue of mitochondrial structure, function, and improving eNOS function within the heart.
SN - 2213-2317
ER -