Calciprotein particles (calcium and phosphate containing nanocrystals) are associated with the development of vascular calcifications (VC) in chronic kidney disease (CKD). As a consequence of a reduced kidney function in chronic kidney disease, phosphate levels rise, leading to increased concentrations of calciprotein particles in the circulation. Literature has shown that circulating calciprotein particles induce vascular calcifications in chronic kidney disease, by affecting mainly the smooth muscle cells (SMCs) in the vascular wall.
Nonetheless, the role of endothelial cells in this pathological process is relatively unknown. In Lian Feenstra’s thesis, the relation between calciprotein particles and endothelial cells was investigated, proposing that the endothelium is an important cell type actually driving the process of calciprotein particle-induced vascular calcifications. Results in this thesis show that endothelial cells play indeed an important role in the development of vascular calcifications. Endothelial cells increase calciprotein particle-induced vascular calcifications via paracrine communication with smooth muscle cells. Also, calciprotein particles impair the metabolism of nitric oxide (NO) in endothelial cells, reducing the endothelial-dependent relaxation of the vascular wall. As a result of calciprotein particle uptake by endothelial cells, the intracellular calcium concentration is disturbed, leading to mitochondrial dysfunction and endothelial cell death. Preventing mitochondrial dysfunction using pharmaceutical interventions seems efficient to preserve endothelial survival. Translation of the preclinical findings to chronic kidney disease patients showed that the presence of calciprotein particles is not only related to vascular calcification development but also vascular remodeling-related processes.
Together, this thesis shows that endothelial cells play an important role in calciprotein particle-induced vascular calcifications and are therefore important targets for future intervention.
