Bin Liu, Mujahid Azfar, Ekaterina Legchenko, James A West, Shaun Martin, Chris Van den Haute, Veerle Baekelandt, John Wharton, Luke Howard, Martin R Wilkins, Peter Vangheluwe, Nicholas W Morrell, Paul D Upton
AIMS: Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase of undefined function, were recently identified in pulmonary arterial hypertension (PAH) patients. ATP13A3 is implicated in polyamine transport but its function has not been fully elucidated. Here, we sought to determine the biological function of ATP13A3 in vascular endothelial cells and how PAH-associated variants may contribute to disease pathogenesis. METHODS AND RESULTS: We studied the impact of ATP13A3 deficiency and overexpression in endothelial cell (EC) models (human pulmonary ECs, blood outgrowth ECs (BOECs) and HMEC-1 cells), including a PAH patient-derived BOEC line harbouring an ATP13A3 variant (LK726X)...
April 16, 2024: Cardiovascular Research