Role of bone-type tissue-nonspecific alkaline phosphatase and PHOSPO1 in vascular calcification

Yuri V. Bobryshev, Alexander N. Orekhov, Igor Sobenin, Dimitry A. Chistiakov

Research output: Contribution to journalArticlepeer-review

Abstract

Matrix vesicle (MV)-mediated mineralization is important for bone ossification. However, under certain circumstances such as atherosclerosis, mineralization may occur in the arterial wall. Bone-type tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes inorganic pyrophosphate (PPi) and generates inorganic phosphate (Pi), which is essential for MV-mediated hydroxyapatite formation. MVs contain another phosphatase, PHOSPHO1, that serves as an additional supplier of Pi. Activation of bone-type tissue-nonspecific alkaline phosphatase (TNAP) in vascular smooth muscle cells precedes vascular calcification. By degrading PPi, TNAP plays a procalcific role changing the Pi/PPi ratio toward mineralization. A pathologic role of bone-type TNAP and PHOSPHO1 make them to be attractive targets for cardiovascular therapy.
Original languageEnglish
Pages (from-to)5821-5828
Number of pages8
JournalCurrent Pharmaceutical Design
Volume20
Issue number37
Publication statusPublished - 2014

Keywords

  • alkaline phosphatase
  • atherosclerosis
  • biomineralization
  • vascular smooth muscle

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