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
收藏
页码：5821 / 5828
页数：8
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