Figure 1. Extracellular pyrophosphate metabolism during phosphate-induced calcification. Extracellular pyrophosphate (PPi) is produced upon ATP hydrolysis by the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1). Pyrophosphate is degraded to phosphate (Pi) by tissue-nonspecific alkaline phosphatase (TNAP). Ectonucleoside triphosphate diphosphohydrolase 1 (eNTPD1), hydrolyzes ATP (and ADP) to Pi. Figure shows changes in the extracellular pyrophosphate metabolism in response to high concentrations of Pi (before hydroxyapatite is formed) and in response to hydroxyapatite. Hydroxyapatite also increases the expression of bone morphogenetic protein 2 (BMP2) and reduces the expression of adult smooth muscle marker 22α (SM22α).