New insight in sepsis capillary leak syndrome : α1AMPK, from the comprehension of key molecular mechanisms to the exploration of a new therapeutic approach
(2021)
Files
Manuscritdethèse-MarineAngé-FINAL-fusionnéOK.pdf
Open Access - Adobe PDF
- 18.53 MB
Details
- Authors
- Supervisors
- Abstract
- Sepsis, which has been recognised as a global health priority by the WHO, is characterized by major endothelial dysfunction and microvascular alterations. The resulting capillary leak syndrome is recognised as an independent prognostic factor for poor sepsis outcome. Our team has previously highlighted the role of AMPK in the pathophysiology of sepsis, and suggested the strengthening of the endothelial barrier as a mechanism involved in this regulation (Castanares-Zapatero et al., 2013). In the present work, we characterise the function of endothelial AMPK in the protection of the vascular barrier during sepsis, and identify Ve-cadherin, Connexin 43 and the p38 MAPK/HSP27 pathway as central mediators of this protection. Furthermore, we identify canagliflozin as a potential new therapeutic strategy to protect against sepsis capillary leak syndrome, and describe the AMPK-dependent protective effects of this molecule on the endothelial barrier.
- Affiliations
Citations
Angé, M. (2021). New insight in sepsis capillary leak syndrome : α1AMPK, from the comprehension of key molecular mechanisms to the exploration of a new therapeutic approach. https://hdl.handle.net/2078.5/115483