title: Calcifying human aortic smooth muscle cells express different bone alkaline phosphatase isoforms, including the novel B1x isoform.
abstract: BACKGROUND
  Vascular calcification, causing cardiovascular morbidity and mortality, is associated with hyperphosphatemia in chronic kidney disease (CKD). In vitro, phosphate induces transdifferentiation of vascular smooth muscle cells to osteoblast-like cells that express alkaline phosphatase (ALP). In vivo, raised serum ALP activities are associated with increased mortality. A new bone ALP isoform (B1x) has been identified in serum from CKD patients. The present study investigated the different ALP isoforms in calcifying human aortic smooth muscle cells (HAoSMCs).
  
  
  METHODS
  HAoSMCs were cultured for 30 days in medium containing 5 or 10 mmol/l β-glycerophosphate in the presence or absence of the ALP-specific inhibitor tetramisole.
  
  
  RESULTS
  All known bone-specific ALP (BALP) isoforms (B/I, B1x, B1 and B2) were identified in HAoSMCs. β-Glycerophosphate stimulated calcification of HAoSMCs, which was associated with increased BALP isoforms B/I, B1x and B2. Tetramisole inhibited the β-glycerophosphate-induced HAoSMC calcification, which was paralleled by the inhibition of the B1x and B/I, but not the other isoforms.
  
  
  CONCLUSIONS
  HAoSMCs express the four known BALP isoforms. B/I, B1x and B2 could be essential for soft tissue calcification. B/I and B1x were more affected by tetramisole than the other isoforms, which suggests different biological functions during calcification of HAoSMCs.
authors: Bone and Mineral Metabolic Unit, Division of Clinical Chemistry, Linköping University, Linköping, Sweden. mathias.loberg-haarhaus @ karolinska.se
authors: Mathias
authors: M
authors: Haarhaus
authors: Hans J
authors: HJ
authors: Arnqvist
authors: Per
authors: P
authors: Magnusson
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D001018:Aortic Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002114:Calcinosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009928:Organ Specificity; D010739:Phospholipase D / Q000378:metabolism; D013773:Tetramisole / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005994:Glycerophosphates; D007527:Isoenzymes; D013773:Tetramisole; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; D010739:Phospholipase D; C065017:glycoprotein phospholipase D; D002118:Calcium; C031463:beta-glycerophosphoric acid