Inhibition of Hmbox1 Promotes Cardiomyocyte Survival and Glucose Metabolism Through Glucokinase (Gck) Activation in Ischemia/Reperfusion Injury
Authors' conclusion
Our studies unravel a new role for the transcriptional repressor Hmbox1 in exercise-induced physiological cardiac growth.
Study context
- Population
- Mice with cardiac I/R injury, cardiomyocytes (neonatal rat, human embryonic stem cell-derived) and human postinfarct heart samples
- Comparison
- Hmbox1 inhibition vs control
Main finding
As reported in the abstract
- Hmbox1 downregulation required for exercise-induced physiological cardiac growth
- Hmbox1 inhibition increased cardiomyocyte size but did not affect proliferation
- Hmbox1 upregulated in human and animal postinfarct cardiac tissue
- Cardiomyocyte-specific Hmbox1 knockout and AAV9-mediated knockdown protected against cardiac I/R injury and HF
- Therapeutic effects with sh-Hmbox1 AAV9 given after I/R injury
- Hmbox1 inhibition activated Akt/mTOR/P70S6K and upregulated Gck: reduced apoptosis, improved mitochondrial respiration and glycolysis
- ETS1 is an upstream negative regulator of Hmbox1; its overexpression protected against cardiac I/R injury
Original publication
Inhibition of Hmbox1 Promotes Cardiomyocyte Survival and Glucose Metabolism Through Gck Activation in Ischemia/Reperfusion Injury. Circulation. Published 6 May 2024. doi:10.
Summarised from the published abstract; every number is checked against it