Figure 5.

An overview the potential involvement of P2Y receptors in arterial calcification. P2Y₆ receptor might trigger a phenotypic switch of vascular cells towards an osteoclast phenotype and by this prevent arterial calcification. P2Y₂ receptor blocks arterial calcification by (i) stimulating phosphoinositide 3-kinases (PI3K) resulting in a reduction in vascular cell apoptosis and halting the bone-like phenotypic switch of vascular cells via less NFkB signaling and IL6 production and (ii) favoring carbonic anhydrase (CA) expression, catalyzing the reaction of water (H2O) and carbon dioxide (CO₂) into hydrogen carbonate (HCO₃⁻) and hydrogen ions (H⁺) leading to extracellular acidification and thus, resorption of the calcium-phosphate crystals. The P2Y₁ receptor might stimulate the arterial calcification process. P2Y₁₂ receptor blockage by clopidogrel potentially halts arterial calcification trough inhibition of tissue non-specific alkaline phosphatase (TNAP) and favoring the transdifferentiation of the vascular cell towards an adipocyte phenotype, thus preventing a bone-like phenotypic switch. P2Y₄ receptor might also be involved in the phenotypic switch of vascular cells to an adipocyte phenotype. Dashed lines represent relevant findings in other cell-types, not yet shown in vascular cells. The term vascular cell covers vascular smooth muscle cells and valve interstitial cells.