Pulmonary arterial Hypertension (PAH) is a severe disease that affects both the pulmonary vasculature and the heart with no curative options. The apelinergic system which can be defined by the cell surface receptor APJ, mostly expressed in the heart and vessels, and its endogenous ligands Apelin and ELABELA appear as a promising therapeutic pathway in the context of cardiovascular dysfunction. Although the beneficial impact of Apelin supply has been well assessed in several experimental model of cardiovascular dysfunction, the potential impact of the recently discovered ELABELA has never been studied in the context of cardiovascular dysfunction/remodeling induced by PAH. On the other hand, agonists acting through the same receptor can be chemically engineered in order to increased their biological efficiency. In the present project and in partnership with IPS therapeutique inc, we propose to evaluate and compare to Apelin-13 the potential cardiovascular effects of the second endogenous APJ ligand ELABELA and originals and optimized compound derivate from apelin structure in the context of PAH.
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