Role of Bone-Type Tissue-Nonspecific Alkaline Phosphatase and PHOSPO1 in Vascular Calcification
Current Pharmaceutical Design,
Yuri V. Bobryshev, Alexander N. Orekhov, Igor Sobenin and Dimitry A. ChistiakovAffiliation:
Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, 1 Ostrovityanova Str., 117997 Moscow, Russia.
AbstractMatrix 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.
Arterial calcification, atherosclerosis, vascular smooth muscle cells, mineralizing matrix vesicles, bone-type tissue-nonspecific alkaline phosphatise, PHOSPO1.
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