Article: article from journal or magazin.
PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.
American Journal of Pathology
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.
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
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