PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.

Details

Serval ID
serval:BIB_EB538C35F2FE
Type
Article: article from journal or magazin.
Collection
Publications
Title
PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.
Journal
American Journal of Pathology
Author(s)
Rutsch F., Vaingankar S., Johnson K., Goldfine I., Maddux B., Schauerte P., Kalhoff H., Sano K., Boisvert W.A., Superti-Furga A., Terkeltaub R.
ISSN
0002-9440 (Print)
ISSN-L
0002-9440
Publication state
Published
Issued date
2001
Volume
158
Number
2
Pages
543-554
Language
english
Abstract
Inogranic pyrophosphate (PPi) inhibits hydroxyapatite deposition, and mice deficient in the PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) Plasma cell membrane glycoprotein-1 (PC-1) develop peri-articular and arterial calcification in early life. In idiopathic infantile arterial calcification (IIAC), hydroxyapatite deposition and smooth muscle cell (SMC) proliferation occur, sometimes associated with peri-articular calcification. Thus, we assessed PC-1 expression and PPi metabolism in a 25-month-old boy with IIAC and peri-articular calcifications. Plasma PC-1 was <1 ng/ml by enzyme-linked immunosorbent assay in the proband, but 10 to 30 ng/ml in unaffected family members and controls. PC-1 functioned to raise extracellular PPi in cultured aortic SMCs. However, PC-1 was sparse in temporal artery lesion SMCs in the proband, unlike the case for SMCs in atherosclerotic carotid artery lesions of unrelated adults. Proband plasma and explant-cultured dermal fibroblast NTPPPH and PPi were markedly decreased. The proband was heterozygous at the PC-1 locus, and sizes of PC-1 mRNA and polypeptide, and the PC-1 mRNA-coding region sequence were normal in proband fibroblasts. However, immunoreactive PC-1 protein was relatively sparse in proband fibroblasts. In conclusion, deficient extracellular PPi and a deficiency of PC-1 NTPPPH activity can be associated with human infantile arterial and peri-articular calcification, and may help explain the sharing of certain phenotypic features between some IIAC patients and PC-1-deficient mice.
Keywords
Arteriosclerosis/enzymology, Arteriosclerosis/pathology, Blotting, Northern, Calcinosis/enzymology, Calcinosis/pathology, Cells, Cultured, Child, Child, Preschool, DNA/chemistry, DNA/genetics, Diphosphates/metabolism, Extracellular Space/chemistry, Extracellular Space/metabolism, Family Health, Female, Fibroblasts/cytology, Fibroblasts/metabolism, Gene Expression Regulation, Enzymologic, Humans, Immunohistochemistry, Infant, Male, Membrane Glycoproteins/blood, Membrane Glycoproteins/deficiency, Microscopy, Confocal, Muscle, Smooth, Vascular/cytology, Muscle, Smooth, Vascular/enzymology, Pedigree, Phosphoric Diester Hydrolases, Pyrophosphatases/metabolism, RNA/genetics, RNA/metabolism, Sequence Analysis, DNA, Skin/cytology, Skin/metabolism
Pubmed
Create date
14/03/2011 16:09
Last modification date
20/08/2019 16:13
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