Heart failure & cardiomyopathies
Checkpoint kinase Wee1 activation drives inflammation and hypertrophy through the protein kinase B/phosphoinositide 3-kinases–nuclear factor κB pathway in cardiomyocytes
Authors' conclusion
Cardiomyocyte Wee1 activation drives inflammation and hypertrophy by directly phosphorylating AKT and activating AKT-nuclear factor κB pathway.
Study context
- Population
- Cardiomyocytes and mouse models of cardiac remodelling (Ang II infusion, transverse aortic constriction (TAC)); hypertrophic cardiac tissue from mice and human patients
Main finding
As reported in the abstract
- Wee1 phosphorylation at Ser642, but not increased expression, in hypertrophic cardiac tissues from mice and human patients
- Knockdown, pharmacological inhibition or mutational inactivation of Wee1 significantly alleviated Ang II-induced cardiomyocyte injuries
- Phosphorylated Wee1 binds the PHD domain of AKT and phosphorylates AKT, activating AKT/PI3K–NF-κB signalling, inflammation and hypertrophy
- Cardiomyocyte-specific Wee1 deficiency protected against cardiac inflammation, remodelling and dysfunction after TAC or Ang II infusion
- Pharmacological Wee1 inhibition attenuated Ang II-induced cardiac remodelling in mice
Original publication
Checkpoint kinase Wee1 activation drives inflammation and hypertrophy through the protein kinase B/phosphoinositide 3-kinases–nuclear factor κB pathway in cardiomyocytes. Eur Heart J. Published 21 May 2025. doi:10.
Summarised from the published abstract; every number is checked against it