Identification of EPHB4 variants in dilated cardiomyopathy patients

Abstract

Cardiac homeostasis relies on the appropriate provision of nutrients and functional specialization of local endothelial cells. Previously we reported in this journal that the endothelial Eph-ephrin signalling, in particular the ligand EphB4, is required for the maintenance of vascular integrity and correct fatty acid transport uptake in the heart via regulating the caveolar trafficking of the fatty acid receptor CD36. In the mouse, endothelial specific loss-of-function of the receptor EphB4, or its ligand ephrin-B2, induces Dilated Cardiomyopathy (DCM) like defects (Luxan et al., 2019). Here, we have identified new rare EPHB4 variants in a cohort of 573 DCM patients. Similar to what we had observed in the EphB4 mutant mice, EPHB4 variants carrying patients show an altered expression pattern of CD36 and CAV1 in the myocardium. Our study confirms a crucial role of the Eph-ephrin signalling pathway, and in particular the receptor EPHB4, in the development of DCM in humans.