Chronic kidney disease (CKD) is associated with increased cardiovascular risk, morphologically characterized by vascular calcification (VC). In CKD, high serum phosphate levels result in enhanced calcification propensity and the formation of circulating crystalline nanoaggregates (calciprotein particles, CPP2) containing calcium, phosphate and serum proteins. CPP2 can induce VC directly and this is recapitulated in vascular smooth muscle cells (VSMCs) in vitro. Under physiological conditions, vascular endothelial cells (ECs), rather than VSMCs are primarily exposed to circulating CPP2. Knowledge on the modulating effects of ECs on VC development is still in its infancy. The aim of this study was to investigate the calcium and bioenergetics signaling in CPP2-induced EC, including using ECs global proteome.