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

被引：38

作者：

Bobryshev, Yuri V. ^{[1
]}

Orekhov, Alexander N. ^{[2
,3
]}

Sobenin, Igor ^{[3
,4
]}

Chistiakov, Dimitry A. ^{[5
]}

机构：

[1] Univ New S Wales, Sch Med Sci, Fac Med, Kensington, NSW 2052, Australia

[2] Skolkovo Innovat Ctr, Atherosclerosis Res Inst, Moscow 143025, Russia

[3] Russian Acad Med Sci, Inst Gen Pathol & Pathophysiol, Lab Cellular Mech Atherogenesis, Moscow 125315, Russia

[4] Russian Cardiol Res & Prod Complex, Med Genet Lab, Moscow 121552, Russia

[5] Pirogov Russian State Med Univ, Dept Med Nanobiotechnol, Moscow 117997, Russia

来源：

CURRENT PHARMACEUTICAL DESIGN | 2014年 / 20卷 / 37期

关键词：

Arterial calcification; atherosclerosis; vascular smooth muscle cells; mineralizing matrix vesicles; bone-type tissue-nonspecific alkaline phosphatise; PHOSPO1; SMOOTH-MUSCLE-CELLS; EXTRACELLULAR PYROPHOSPHATE METABOLISM; NECROSIS-FACTOR-ALPHA; MATRIX VESICLES; GROWTH-PLATE; ARTERIAL CALCIFICATION; OSTEOGENIC DIFFERENTIATION; ATHEROSCLEROTIC ARTERIES; SKELETAL MINERALIZATION; INORGANIC PYROPHOSPHATE;

D O I：

10.2174/1381612820666140212193011

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：5821 / 5828

页数：8

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