Grant: CIHR Fellowship

Urgent stabilization of hemodynamics and organ/tissue perfusion is a cornerstone in septic shock treatment, which seriously affects the myocardial function and the vascular tree. Catecholamines treatment, in concert with fluid resuscitation, has long been recommended. However, not all patients respond positively and current controversy questions the efficacy-to-safety profile of this drug family. Considering that current therapeutic approaches are less than optimal, it is time to identify new safer and life-saving alternative therapies. Our group and others recently demonstrated that the endogenous apelinergic system is a compelling target to sustain cardiovascular function in septic shock. The apelin receptor stimulation through infusion of either Apelin-13 or ELABELA improves hemodynamics, limits cardiovascular dysfunction as well as mortality in experimental septic shock. Considering this proven potential therapeutic impact of the apelin receptor stimulation, the purpose of the current project is to study the cellular processes involved in this cardioprotection in order to ultimately identify novel analogs with improved therapeutic capabilities. By generating novel bias agonists of the apelinergic system, we propose a two years project to study how the apelin receptor regulates myocardial cells function to increase their performance in face of great hemodynamic stress in the context of septic shock. Furthermore, this project could be the first pre-clinical proof of concept for the therapeutic efficiency of GPCR biased ligand in the research field of critical care illness.