Calcifying Human Aortic Smooth Muscle Cells Express Different Bone Alkaline Phosphatase Isoforms, Including the Novel B1x Isoform
2013 (English)In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 50, no 2, 167-174 p.Article in journal (Refereed) Published
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 beta-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. beta-Glycerophosphate stimulated calcification of HAoSMCs, which was associated with increased BALP isoforms B/I, B1x and B2. Tetramisole inhibited the beta-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.
Place, publisher, year, edition, pages
S. Karger, 2013. Vol. 50, no 2, 167-174 p.
Bone-specific alkaline phosphatase, Chronic kidney disease, Human aortic smooth muscle cells, Isoforms, Phosphate, Vascular calcification
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-90089DOI: 10.1159/000346161ISI: 000314995500008OAI: oai:DiVA.org:liu-90089DiVA: diva2:612396
Funding Agencies|Ingrid Asps Foundation for Nephrology Research at Linkoping University||County Council of Ostergotland||Swedish Association for Kidney Patients||2013-03-212013-03-192014-11-06