Fibroblast growth factor (FGF)-23 and fetuin-A in calcified carotid atheroma.
OBJECTIVE
Human atheroma calcification occurs secondary to repetitive injury/remodelling of the vessel wall and might be initiated by adherence of mineral-loaded fetuin-A whether or not professional matrix mineralizing cells are present. The aim was to investigate the contribution of fibroblast growth factor (FGF)-23 to ectopic mineralization.


RESULTS
Serial sections of formalin-fixed paraffin-embedded human carotid atheroma (n = 54) were investigated with respect to (i) size and distribution of calcific deposits, (ii) indicators of chondrogenic/osteogenic transformation, and (iii) expression of fetuin-A and FGF-23. All specimens were calcified and SOX-9, collagen type II, cathepsin-K, fetuin-A and FGF-23 expression was seen in 46, 53, 53, 54 and 48 specimens, respectively. The intracellular detection of FGF-23 (45/48) indicates local synthesis. Whereas fetuin-A expression was seen also within areas of vascular smooth muscle actin-positive cells adjacent to calcific deposits, FGF-23 expression was apparently restricted to the mineralization-prone areas. Both local expression and FGF-23 serum concentrations were significantly associated with the degree of atheroma calcification.


CONCLUSIONS
Besides the induction of bone islets and subsequent mineral deposition, severe remodelling of the vessel wall is sufficient to create a mineralizable fetuin-A-attracting microenvironment. FGF-23 might contribute to the formation of proper mineral, i.e. control local phosphate concentration.
Voigt
Mathias
M
Departments of Paediatrics, University of Rostock, Rostock, Germany.
Fischer
Dagmar-Christiane
DC
Rimpau
Max
M
Schareck
Wolfgang
W
Haffner
Dieter
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001798:Blood Proteins / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; C000717427:FGF23 protein, human; D060749:alpha-2-HS-Glycoprotein; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23