Figure 4.

Mechanisms underlying cyanate or (modified) LDL-induced endothelial dysfunction. Increased cyanate levels as in CKD patients induce cellular signaling triggering endothelial dysfunction as displayed in increased vascular stiffness (A) as well as enhanced endothelial inflammation, triggering the recruitment and adhesion of inflammatory cells (B). Furthermore, cyanate-induced protein carbamylation leads to carbamylated low-density lipoprotein (cLDL), which can trigger oxidative stress and cell death (C) and can increase thrombotic risk through increases in tissue factor and PAI (D). In addition, LDL was shown to contribute to endothelial inflammation by upregulating pro-inflammatory cytokines and adhesion molecules, triggering inflammatory cell recruitment and adhesion (E). AP-1 = activator protein-1; cLDL = carbamylated LDL; EndoG = endonuclease G; eNOS = endothelial nitric oxide synthase; ICAM = intracellular adhesion molecule; LDL = low density lipoprotein; LOX-1 = Lectin-like oxidized low density lipoprotein receptor-1; MAPK = mitogen activated protein kinase; NF-kB = nuclear factor kappa B; NO = nitric oxide; PAI = plasminogen activator inhibitor; TF = tissue factor; TNF = tumor necrosis factor.