Targeting E3 Ubiquitin Ligase Hrd1 Prevents Myocardial Ischemia-Reperfusion Injury Through Enhancing ALDH2 Enzymatic Activity
Authors' conclusion
Our findings demonstrated a previously unidentified crucial role of cardiac EC Hrd1 in myocardial I/R injury.
Study context
- Population
- Mouse hearts subjected to sham surgery or myocardial I/R injury; Hrd1 knockout, endothelial cell (EC)-specific Hrd1 deficiency and EC-specific Hrd1 overexpression mice
Main finding
As reported in the abstract
- Protein ubiquitination exacerbates endothelial dysfunction after myocardial I/R injury
- Significant upregulation of E3 ubiquitin-protein ligase Hrd1 in CD45+ ECs
- Endothelial Hrd1 protein increased in response to I/R in vivo, in humans and mice
- Genetic ablation of Hrd1 significantly alleviated MI, endothelial dysfunction and inflammatory cell infiltration after I/R
- Hrd1 promoted K33-linked polyubiquitination of ALDH2, inhibiting formation of its active tetramers, acting via NO/cGMP/PKG signalling
- Pharmacological inhibition of Hrd1 robustly ameliorated myocardial I/R injury and endothelial dysfunction
Original publication
Targeting E3 Ubiquitin Ligase Hrd1 Prevents Myocardial Ischemia-Reperfusion Injury Through Enhancing ALDH2 Enzymatic Activity. Circulation. Published 17 April 2026. doi:10.
Summarised from the published abstract; every number is checked against it