FIGURE 2.

Klotho may suppress inflammation and oxidative stress in VSMCs and endothelial cells. Phosphate entry in VSMCs through PiT1 carrier stimulates the production of reactive oxygen species such as superoxide (${\mathrm{O}}_2^{-}$) and hydrogen peroxide (H₂O₂). These compounds activate nuclear factor-κB signalling pathways and increase the expression of osteogenic factors in VSMCs that are stimulated to develop an osteoblast-like phenotype. Thus these cells can release membrane vesicles containing hydroxyapatite crystals and cause artery wall calcification. In addition to these mechanisms, sodium overload increases sodium content in the artery wall. This causes local inflammation and production of ROS and O₂ in endothelial cells, impairing nitric oxide synthesis and its vasodilating activity.