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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Role of Bone-Type Tissue-Nonspecific Alkaline Phosphatase and PHOSPO1 in Vascular Calcification

Author(s): Yuri V. Bobryshev, Alexander N. Orekhov, Igor Sobenin and Dimitry A. Chistiakov

Volume 20 , Issue 37 , 2014

Page: [5821 - 5828] Pages: 8

DOI: 10.2174/1381612820666140212193011

Price: $65

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.


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