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.
Keywords: Arterial calcification, atherosclerosis, vascular smooth muscle cells, mineralizing matrix vesicles, bone-type tissue-nonspecific alkaline phosphatise, PHOSPO1.
Current Pharmaceutical Design
Title:Role of Bone-Type Tissue-Nonspecific Alkaline Phosphatase and PHOSPO1 in Vascular Calcification
Volume: 20 Issue: 37
Author(s): Yuri V. Bobryshev, Alexander N. Orekhov, Igor Sobenin and Dimitry A. Chistiakov
Affiliation:
Keywords: Arterial calcification, atherosclerosis, vascular smooth muscle cells, mineralizing matrix vesicles, bone-type tissue-nonspecific alkaline phosphatise, PHOSPO1.
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.
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Bobryshev V. Yuri, Orekhov N. Alexander, Sobenin Igor and Chistiakov A. Dimitry, Role of Bone-Type Tissue-Nonspecific Alkaline Phosphatase and PHOSPO1 in Vascular Calcification, Current Pharmaceutical Design 2014; 20 (37) . https://dx.doi.org/10.2174/1381612820666140212193011
DOI https://dx.doi.org/10.2174/1381612820666140212193011 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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